In the summer of 2015, a 7-year-old named Hassan was admitted to the burn unit of the Ruhr University Childrens Hospital in Bochum, Germany, with red, oozing wounds from head to toe.

It wasnt a fire that took his skin. It was a bacterial infection, resulting from an incurable genetic disorder. Called junctional epidermolysis bullosa, the condition deprives the skin of a protein needed to hold its layers together and leads to large, painful lesions. For kids, its often fatal. And indeed, Hassans doctors told his parents, Syrian refugees who had fled to Germany, the young boy was dying.

The doctors tried one last thing to save him. They cut out a tiny, unblistered patch of skin from the childs groin and sent it to the laboratory of Michele de Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia. De Lucas team used a viral vector to ferry into Hassans skin cells a functional version of the gene LAMB3, which codes for laminin, the protein that anchors the surface of the skin to the layers below.

advertisement

Then the scientists grew the modified cells into sheets big enough for Ruhr University plastic surgeons Tobias Hirsch and Maximilian Kueckelhaus to graft onto Hassans raw, bedridden body, which they did over the course of that October, November, and the following January.

It worked better than the boys doctors could have imagined. In 2017, de Luca, Hirsch, Kueckelhaus, and their colleagues reported that Hassan was doing well, living like a normal boy in his lab-grown skin. At the time though, there was still a big question on all their minds: How long would it last? Would the transgenic stem cells keep replenishing the skin or would they sputter out? Or worse could they trigger a cascade of cancer-causing reactions?

advertisement

Today, the same team is out with an update. Five years and five months after the initial intervention, Hassan is still, for the most part, thriving in fully functional skin that has grown with the now-teenager. He is attending school, and playing sports with his friends and siblings, though he avoids swimming due to blistering in the areas that werent replaced by the lab-grown skin. One of his favorite activities is a pedal-powered go kart. There are no signs his modified stem cells have lost their steam, and no traces of tumors to be found.

The encouraging follow-up data has been instrumental in moving forward a larger clinical trial of the approach, offering hope to the 500,000 epidermolysis bullosa patients worldwide currently living without treatment options.

We were astonished by the speedy recovery, Kueckelhaus, now at University Hospital Muenster, told STAT via email. But experience from skin transplantation in other settings made him and his colleagues wary of the grafts failing as the months and years wore on. Thankfully, wrote Kueckelhaus, those fears never materialized. We are very happy to be able to prove that none of these complications appeared and the genetically modified skin remains 100% stable. The chances are good that he will be able to live a relatively normal life.

Over the last five years, Hassans team of doctors and researchers has put his new skin through a battery of tests checking it for sensitivity to hot and cold, water retention, pigmentation and hemoglobin levels, and if it had developed all the structures youd expect healthy skin to have, including sweat glands and hair follicles. Across the board, the engineered skin appeared normal, without the need for moisturizers or medical ointments. The only flaw they found was that Hassans skin wasnt as sensitive to fine touch, especially in his lower right leg. This mild neuropathy they attributed not to the graft itself, but to how that limb was prepared doctors used a more aggressive technique that might have damaged the nerves there.

The team also used molecular techniques to trace the cells theyd grown in the lab as they divided and expanded over Hassans body. They found that all the different kinds of cells composing the boys new skin were being generated by a small pool of self-renewing stem cells called holoclone-forming cells, carrying the Italian teams genetic correction.

This was quite an insight into the biology of the epidermis, said de Luca. Its an insight he expects will have huge consequences for any efforts to advance similar gene therapies for treating other diseases affecting the skin. You have to have the holoclone-forming cells in your culture if you want to have long-lasting epidermis, he said.

The approach pioneered by de Lucas team will soon be headed for its biggest clinical test yet, after nearly a decade of fits and starts. They expect to begin recruiting for a multi-center Phase 2/3 trial sometime next year.

De Luca first successfully treated a junctional EB patient in 2005. But then a change to European Union laws governing cell and gene therapies forced his team to stop work while they found ways to comply with the new rules. It took years of paperwork, building a manufacturing facility, and spinning out a small biotech company called Holostem to be ready to begin clinical research again. Hassan came along right as they were gearing up for a Phase 1 trial, but data from the boys case, which was granted approval under a compassionate use provision, convinced regulators that the cell grafts could move to larger, more pivotal trials, according to de Luca.

We didnt cure the disease, he told STAT. But the skin has been restored, basically permanently. We did not observe a single blister in five years. The wound healing is normal, the skin is robust. From this point of view, the quality of life is not even comparable to what it was before.

Read this article:

Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT

Gene therapy is a powerful developing technology that has the potential to address myriad diseases. For example, Huntington's disease, a neurodegenerative disorder, is caused by a mutation in a single gene, and if researchers could go into specific cells and correct that defect, theoretically those cells could regain normal function.

A major challenge, however, has been creating the right "delivery vehicles" that can carry genes and molecules into the cells that need treatment, while avoiding the cells that do not.

Now, a team led by Caltech researchers has developed a gene-delivery system that can specifically target brain cells while avoiding the liver. This is important because a gene therapy intended to treat a disorder in the brain, for example, could also have the side effect of creating a toxic immune response in the liver, hence the desire to find delivery vehicles that only go to their intended target. The findings were shown in both mouse and marmoset models, an important step towards translating the technology into humans.

A paper describing the new findings appears in the journal Nature Neuroscience on December 9. The research was led by Viviana Gradinaru (BS '05), professor of neuroscience and biological engineering, and director of the Center for Molecular and Cellular Neuroscience.

The key to this technology is the use of adeno-associated viruses, or AAVs, which have long been considered promising candidates for use as delivery vehicles. Over millions of years of evolution, viruses have evolved efficient ways to gain access into human cells, and for decades researchers have been developing methods to harness viruses' Trojan-Horse-like abilities for human benefit.

AAVs are made up of two major components: an outer shell, called a capsid, that is built from proteins; and the genetic material encased inside the capsid. To use recombinant AAVs for gene therapy, researchers remove the virus's genetic material from the capsid and replace it with the desired cargo, such as a particular gene or coding information for small therapeutic molecules.

"Recombinant AAVs are stripped of the ability to replicate, which leaves a powerful tool that is biologically designed to gain entrance into cells," says graduate student David Goertsen, a co-first author on the paper. "We can harness that natural biology to derive specialized tools for neuroscience research and gene therapy."

The shape and composition of the capsid is a critical part of how the AAV enters into a cell. Researchers in the Gradinaru lab have been working for almost a decade on engineering AAV capsids that cross the blood-brain barrier (BBB) and to develop methods to select for and against certain traits, resulting in viral vectors more specific to certain cell types within the brain.

In the new study, the team developed BBB-crossing capsids, with one in particular AAV.CAP-B10that is efficient at getting into brain cells, specifically neurons, while avoiding many systemic targets, including liver cells. Importantly, both neuronal specificity and decreased liver targeting was shown to occur not just in mice, a common research animal, but also in laboratory marmosets.

"With these new capsids, the research community can now test multiple gene therapy strategies in rodents and marmosets and build up evidence necessary to take such strategies to the clinic," says Gradinaru. "The neuronal tropism and decreased liver targeting we were able to engineer AAV capsids for are important features that could lead to safer and more effective treatment options for brain disorders."

The development of an AAV capsid variant that works well in non-human primates is a major step towards the translation of the technology for use in humans, as previous variants of AAV capsids have been unsuccessful in non-human primates. The Gradinaru lab's systematic in vivo approach, which uses a process called directed evolution to modify AAV capsids at multiple sites has been successful in producing variants that can cross the BBBs of different strains of mice and, as shown in this study, in marmosets.

"Results from this research show that introducing diversity at multiple locations on the AAV capsid surface can increase transgene expression efficiency and neuronal specificity," says Gradinaru. "The power of AAV engineering to confer novel tropisms and tissue specificity, as we show for the brain versus the liver, has broadened potential research and pre-clinical applications that could enable new therapeutic approaches for diseases of the brain."

The paper is titled "AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset." Goertsen; Nicholas Flytzanis (PhD '18), the former scientific director of the CLARITY, Optogenetics and Vector Engineering Research(CLOVER)Center of Caltech's Beckman Institute; and former Caltech postdoctoral scholar Nick Goeden are co-first authors. Additional coauthors are graduate student Miguel Chuapoco, and collaborators Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Ip, and James Pickel.

Funding was provided by the Defense Advanced Research Projects Agency, the National Institutes of Health, and the National Sciences and Engineering Research Council of Canada.

Flytzanis, Goeden, and Gradinaru are co-founders of Capsida Biotherapeutics, a Caltech-led startup company formed to develop AAV research into therapeutics.

Read the rest here:

New Technology is One Step Closer to Targeted Gene Therapy - Caltech

By Anthony O. Goriainoff

N4 Pharma PLC said Monday that it will focus its resources on advancing its work on gene therapy, and that it will continue its vaccine-delivery efforts in conjunction with partners and working on specific proprietary products.

The AIM-listed pharmaceutical company said the preliminary results from mouse immunogenicity studies carried out by Evotec SE using Covid-19 didn't show meaningful immunological response, and that this brought into question the whole study. The company said it will concentrate future vaccine work through its material transfer agreements [MTA] and that it was in advanced discussions with another company focusing on mRNA delivery with a view to scoping the work to be undertaken under a new MTA.

The company said that although the results on the vaccine work from Evotec were unexpected, the proof-of-concept data collated to date has been sufficient to allow it to sign MTAs with potential vaccine collaborators.

"We expect other collaborations will follow, so it makes sense to continue the vaccine platform optimization with collaborators who own their own DNA plasmids and mRNA compounds. This will allow us to focus internal efforts on developing commercial products in the gene therapy space," Chief Executive Nigel Theobald said.

Write to Anthony O. Goriainoff at anthony.orunagoriainoff@dowjones.com

See the article here:

N4 Pharma to Focus Resources on Advancing Gene Therapy Work - MarketWatch

The Cystic Fibrosis Foundationis funding three new early-stage research awards worth more than $1.8 million to bolster the development of potential gene therapies for cystic fibrosis (CF).

This funding will support critical early steps necessary for the development of genetic therapies for cystic fibrosis, William Skach, MD, executive vice-president and chief scientific officer of the CF Foundation, said in a press release. These promising programs are tackling difficult challenges such as efficient therapeutic delivery of diverse genetic cargos and evasion or modulation of the immune systems response to gene delivery vehicles.

Gene therapy works by adding a new gene or replacing or repairing a mutated gene inside cells in the body. To get gene therapy into the cells, it first must be packed into a carrier, usually a harmless virus. However, other carriers exist that may deliver gene therapy.

Carmine Therapeutics was awarded more than $766,000 to test one such alternative type of carrier. The company plans to use tiny particles, called vesicles, that naturally bud off from red blood cells to deliver a healthy copy of cystic fibrosis transmembrane conductance regulator (CFTR) the gene mutated in people with CF into lung cells. Unlike other carriers, which sometimes trigger an immune response, the vesicles are expected to be well-tolerated by the immune system, even upon repeat administration.

If a viral carrier must be used, the bodys immune response should be blocked to allow repeat administration. GenexGen was awarded close to $595,000 to develop a way to lessen the immune response to a viral carrier. The company is testing an approach that uses CRISPR a kind of molecular scissors that can cut pieces of DNA to target a certain gene that plays a key role in the immune system. The goal is to turn off that gene temporarily, thus allowing gene therapy to be delivered by a virus.

Finally, Specific Biologics was awarded more than $527,000 to test a CRISPR-based approach to make precise changes in DNA and thereby correct (edit) three common CFTR mutations in CF: G542X, R553X, and W1282X. Each of these mutations results in a stop codon in the middle of the gene and a shorter protein that ends up getting degraded by the cells. If successful, the approach is expected to work for any mutation.

The award will support preclinical testing of an inhaled medicine that uses tiny fat particles to help the gene-editing molecules enter the cells more easily.

The awards are part of the foundations Path to a Cure, an initiative whose goal is to accelerate the development of therapeutic strategies that address the root cause of CF.

See the original post here:

CF Foundation Funding Bolsters Gene Therapy Research - Cystic Fibrosis News Today

Jeremy Moeller/Getty Images

Significant advancements in the treatment of relapsed or refractory large B-cell lymphoma are on the horizon. At the American Society of Hematology meeting, this weekend, both Bristol Myers Squibband Kite Pharma presented promising data from CAR-T programs aimed at this disease.

At ASH, BMS unveiled data that showedBreyanzi(liso-cel), a CD19-directed CAR-T cell therapy, as a second-line treatment in adults with relapsed or refractory large B-cell lymphoma,outperformed the current standard of carefor patients in second-line relapsed or refractory LBCL, significantly improving event-free survival (EFS). BMS said that only a small portion of patients who have relapsed or refractory large B-cell lymphoma (LBCL) experience long-term benefits with high-dose chemotherapy and stem cell transplant. Data from the pivotal Phase III TRANSFORM study showed that Breyanzi significantly improved median event-free survival with a median of 10.1 months. Standard of care treatment only offered an improvement of 2.3 months with a 65% improvement.

Data showed that 86% of Breyanzi patients achieved a complete or partial response, with 66% of patients achieving a complete response. In comparison, only 48% of standard of care patients achieved the same response, with only 39% of those reaching a complete response.

Median progression-free survival was significantly longer withBreyanzicompared to standard of care, 14.8 months vs. 5.7 months.

Additionally, results from an analysis of patient reported outcomes from the TRANSFORM study showed favorable improvement in most patient reported outcomes. That includes an improved or maintained health-related quality of life for patients who were treated with Breyanzicompared to those treated with the standard of care treatment.

Kite Pharma, a subsidiary of Gilead Sciences, showcased its own data in second-line relapsed/refractory large B-cell lymphoma (LBCL), the same indication as BMS Breyanzi. Data from the landmark Phase III ZUMA-7 study of Yescarta (axicabtagene ciloleucel) showed a 2.5 fold increase in patients who were alive at two years and had not required the need for additional cancer treatment or experienced cancer progression. Also, the data showed a four-fold greater median event-free survival for Yescarta compared to standard of care.

Kite said that improvements in EFS with Yescarta were consistent across patient subgroups, including the elderly, those with primary refractory disease, high-grade B-cell lymphoma including double-hit and triple-hit lymphoma and double expressor lymphoma.

Yescarta was the first CAR T-cell therapy to be approved by the U.S. Food and Drug Administrationfor the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

Additionally, Kite announced significant long-term data showcasing the CAR-T therapys ability to provide meaningful improvements in quality of life compared with standard of care. Also at ASH, Kite unveiled data that showed Yescarta provided a five-year overall survival rate of 42%. Among those patients who saw a complete response to the CAR-T treatment, the five-year overall survival rate was 64.4%.

Perhaps most significantly, Kite said that among Yescarta patients who were still alive after five years, 92% needed no additional treatment since that first infusion of the CAR-T therapy. This suggests a potential cure for some of the patients, Kite said, in its announcement.

Other cell therapy data presented at ASH include:

bluebird Gene Therapy Improves Lives of Sickle Cell Patients

bluebird bio'slovo-celis showing promisein a Phase I/II study in sickle cell. Data from two cohorts of the largest sickle cell gene therapy program to date is showing patients treated with lovo-cel are seeing a continued complete resolution of severe vaso-occlusive events (VOE) after six years.

The VOEs are defined as episodes of acute pain with no medically determined cause other than vaso-occlusion. That means that lovo-cel, a lentiviral gene therapy, has the potential to improve day-to-day life in sickle cell patients by eliminating the painful issues associated with the disease that can occur several times per month.

Additionally, the patients have achieved near normal levels of key hemolysis markers and experienced sustained improvements in patient-reported quality of life following treatment.

The bluebird gene therapy is designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients blood stem cells. Once the gene is added, their red blood cells are able to produce anti-sickling hemoglobin (HbAT87Q), which reduces the sickled blood cells that cause the disease.

Janssens CAR-T Hammers Multiple Myeloma

At ASH, Janssenannounced data from a Phase Ib/II study that showed CAR-T therapy cilta-cel (ciltacabtagene autoleucel) provided anoverall response rate of 98%in patients with relapsed and/or refractory multiple myeloma.

The company said that cilta-cel, an investigational B-cell maturation antigen (BCMA)-directed CAR-T therapy, showed that patients who received an infusion continued to demonstrate deep and durable responses. Data showed that 83% of patients in the study achieved a stringent complete response (sCR) at 22 months. That is an 80% increase from the 18-month median follow-up presented earlier this year at the American Society of Clinical Oncology meeting.

Also, two-year progression free survival and overall survival rates were 61% and 74%, respectively.

Poseida Sees Promise in CAR-T as it Winds Down Autologous Program

Interim results from Poseida'sPhase I/II PRIME study of P-BCMA-101for the treatment of relapsed/refractory multiple myeloma show strong anti-tumor activity in patients with advanced forms of the disease. P-BCMA-101 in combination with rituximab achieved an improved overall response rate of 78% and 100% overall survival.

P-BCMA-101 is a non-viral transposon-based autologous CAR-T. The data from the PRIME study have been used to inform the companys development of its first allogeneic program, P-BCMA-ALLO1, also being developed in the same indication. In November, Poseida announced that it iswinding down the P-BCMA-101 autologous programin favor of the allogeneic program, P-BCMA-ALLO1.

Read more here:

BMS and Kite Unveil CAR-T Successes in Lymphoma - BioSpace

Gene therapy is still in its infancy and has yet to achieve its full potential. First-generation gene therapies have been challenged by safety issues due to their inability to target cells and organs without also penetrating non-targeted cells and organs, especially the liver. Capsida's proprietary, targeted, non-invasive gene therapy technology allows more selective targeting of specific tissues and cells, overcoming many of the problems associated with first-generation gene therapies, specifically off-target cell and organ activity. In addition, it allows the gene therapy to be delivered non-invasively through intravenous (IV) administration. The company's already strong leadership team is poised to actualize the promise of gene therapy with the addition of Mr. Anastasiou and the promotions of Drs. Flytzanis and Goeden.

"I can't imagine a more exciting time to join this organization," said Mr. Anastasiou. "Capsida is enabling gene therapy to become what the industry, physicians, and patients have been dreaming it will be. Our patent-protected technology allows the targeting of cells and organs while limiting the negative impact on non-targeted areas, and can be applied across multiple therapeutic areas. Another important benefit of our technology is that we are able to deliver the gene therapy non-invasively through IV administration. I'm honored to lead this talented team to achieve Capsida's potential and to improve and even save patients' lives."

Mr. Anastasiou joins Capsida from Lundbeck, where he was an executive vice president and a member of the executive committee, reporting to the CEO. As the president of Lundbeck's U.S. and Canadian business operations, Mr. Anastasiou has built organizations from the ground up. He brings significant leadership experience managing diverse organizations and bringing them together to achieve common goals. He led as many as 1,200 employees and achieved net revenues of $1.5 billion. During his 12-year tenure at Lundbeck, Mr. Anastasiou held several progressive leadership positions, playing a pivotal role in developing and launching multiple products and building the company's cross-functional capabilities. Mr. Anastasiou serves on the Board of PhRMA and the global advisory board for the Healthcare Businesswomen's Association. Mr. Anastasiou begins his new role with Capsida on January 3, 2022.

"We're thrilled to welcome Peter as Capsida's new CEO," said Beth Seidenberg, M.D., founding managing director at Westlake Village BioPartners, one of the company's lead investors, and Capsida board member. "Peter has deep industry expertise, a broad network, and significant public company experience, which will be valuable as Capsida grows. In addition, his strong track record of success demonstrates he is a visionary leader who will be able to deliver on the promise of targeted non-invasive gene therapy to help underserved patients and achieve business success."

"During his tenure at Lundbeck, Peter has created significant shareholder value, creating and leading organizations and successful blockbuster product launches," said Clare Ozawa, Ph.D., managing director at Versant Ventures, one of Capsida's lead investors, and Capsida board member."Under Peter's leadership, we will continue to build Capsida as the industry's leading targeted, non-invasive gene therapy company with the ability to transform the lives of patients with life-threatening genetic disorders."

Prior to Lundbeck, Mr. Anastasiou held management roles at Neuronetics, Inc., Bristol-Meyers Squibb Company, and Eli Lilly and Company. He holds an MBA from the Kelley School of Business at Indiana University, and a B.A. in economics and management from Albion College.

Capsida co-founders Nicholas Flytzanis, Ph.D., promoted to CSO and Nick Goeden, Ph.D., promoted to CTO

In addition to Mr. Anastasiou's appointment, Capsida announced that Dr. Flytzanis has been promoted toCSO and Dr. Goeden has been promoted to CTO.

"The promotions of Drs. Flytzanis and Goeden are in recognition of the significant contributions they have made since co-foundingCapsida in 2019," said Mr. Anastasiou. "Their steadfast commitment to delivering on the promise of Capsida's differentiated, non-invasive gene therapy platform has been a key driver behind many of the company's early achievements."

"Drs. Flytzanis' and Goeden's strong scientific and technical expertise and know-how have already delivered results in the startup of Capsida based on Caltech'sbasic research on targeted non-invasive gene delivery to the brain," said Capsida co-founder Viviana Gradinaru, Ph.D. "Their promotions are timely as Capsida enters the phase of delivering from the lab and for the patients."

Prior to co-founding Capsida, Dr. Flytzanis served as scientific director of the CLOVER research center at the California Institute of Technology (Caltech), leading an interdisciplinary team to develop and disseminate emerging technologies focused on the cross-section of neurological research and gene therapy. His research spans the fields of tissue clearing and imaging, optogenetics and rodent behavior, and adeno-associated virus (AAV) engineering and gene therapy, with collaborations across multiple institutions. During his Ph.D., Dr. Flytzanis applied protein engineering and directed evolution across biological modalities, with a focus on developing AAVs as therapeutic tools for neurological disease.

Dr. Flytzanis holds a Ph.D. in biology from Caltech and a B.S. in biology from the Massachusetts Institute of Technology.

Prior to co-founding Capsida, Dr. Goeden led a team developing the novel adeno-associated virus (AAV) engineering technology underlying Capsida's biologically driven gene therapy platform. During his tenure as a postdoctoral fellow in Dr. Gradinaru's lab at Caltech, he developed high-throughput methods for screening combinatorial libraries to explore the AAV fitness landscape and engineered novel AAVs with high efficiency and specificity for the rodent and primate brain. During his Ph.D., Dr. Goeden developed a novel organ bioreactor to study real-time metabolomics in diseased states, exploring the relationship between gene expression and the pathophysiology of neurodevelopmental disorders.

Dr. Goeden holds a Ph.D. in neuroscience from The University of Southern California and a B.S. in biology from Caltech.

About Capsida Biotherapeutics

Capsida Biotherapeutics Inc. is an industry-leading gene therapy platform company creating a new class of targeted, non-invasive gene therapies for patients with debilitating and life-threatening genetic disorders. Capsida's technology allows for the targeted penetration of cells and organs, while limiting collateral impact on non-targeted cells and organs, especially the liver. This technology allows for the delivery of the gene therapy in a non-invasive way through intravenous administration. Capsida's technology is protected by a growing intellectual property portfolio which includes more than 30 patent applications and one issued U.S. patent 11,149,256. The company is exploring using the technology across a broad range of life-threatening genetic disorders. Its initial pipeline consists of multiple neurologic disease programs. The company has strategic collaborations with AbbVie and CRISPR, which provide independent validation of Capsida's technology and capabilities. Capsida is a multi-functional and fully integrated biotechnology company with proprietary adeno-associated virus (AAV) engineering, multi-modality cargo development and optimization, translational biology, process development and state-of-the-art manufacturing, and broad clinical development experience. Capsida's biologically driven, high-throughput AAV engineering and cargo optimization platform originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at the California Institute of Technology. Visit us at http://www.capsida.com to learn more.

SOURCE Capsida Biotherapeutics

More:

Capsida Biotherapeutics Poised to Capitalize on Industry-leading Gene Therapy Technology With New CEO, CSO, and CTO - PRNewswire

DUBLIN--(BUSINESS WIRE)--The "Gene Editing Global Market Report 2021: COVID-19 Growth and Change to 2030" report has been added to ResearchAndMarkets.com's offering.

The global gene editing market is expected to grow from $4.25 billion in 2020 to $4.53 billion in 2021 at a compound annual growth rate (CAGR) of 6.6%. The market is expected to reach $7.27 billion in 2025 at a CAGR of 12.6%.

Major players in the gene editing market are CRISPR, GenScript USA Inc., Horizon Discovery Group plc, Integrated DNA Technologies and New England Biolabs.

The gene editing market consists of sales of gene editing technology such as CRISPR/CAS9, zinc finger nucleus, and talens and related services. Gene editing technology allows genetic material to change genetic code at particular location in a genome. It involves cell line engineering, animal genetic engineering and plant genetic engineering.

The gene editing market covered in this report is segmented by technology into CRISPR, TALEN, ZFN. It is also segmented by end users into biotechnology, pharmaceutical, contract research organization and by application into animal genetic engineering, plant genetic engineering, cell line engineering.

Infectious diseases are constantly on the rise. For instance, according to the World Health Organization (WHO), infectious diseases kill more than 17 million people per year. In addition to that, according to the AP-NORC (a research initiative by the Associated Press and the University of Chicago) survey, out of 1,067 adults in the US surveyed, 71% are in favor of gene editing for the treatment of incurable, hereditary diseases such as Huntington's disease and 67% of Americans support the use of gene editing to prevent diseases such as cancer.

Ethical issues in general public with respect to gene editing is one of the major restraining factors for the market. Many researchers and ethicist have argued against gene editing due to different reasons such as off-target effect (edits in the wrong place), mosaicism (when only some of the cells carry the edits) and safety concerns. Some even argued that gene editing will lead to the creation of classes of individuals who will be genetically modified to be able to do things that a normal human being is not supposed to do according to the laws of nature. Due to these reasons, gene editing is still not considered to be safe and effective by many nations and international organizations.

Gene editing (also called genome editing) is a group of technologies that allow the researchers to change an organism's DNA by adding, removing or altering genetic material at particular locations in the genome. The emergence of advanced genome editing techniques is one of the major trend in the gene editing market.

The new techniques in genome editing are relatively inexpensive and can be used in a variety of application areas such as improving the food supply in agriculture, rectifying specific genetic mutations in the human genome and preventing the spread of diseases. For instance, CRISPR-Cas9 is a gene editing technique and stands for Clustered Regularly Interspace Short Palindromic Repeats.

The technique uses a strand of DNA as molecular scissors used to make cuts in DNA at specific points to make space to add new genomes. This technique is faster, cheaper, more accurate and efficient than other existing genome editing methods. Companies investing in CRISPR technology are Crispr therapeutics (CRSP), Intellia Therapeutics (NTLA), and Editas medicine.

The rising infectious diseases acts as one of the major drivers of the gene editing market. Gene editing techniques are used for detection of infectious diseases such as HIV. Infectious diseases are caused by microorganisms like bacteria, viruses, fungi, and parasites. Gene therapy treats the infectious diseases by blocking the replication of the infectious agent that causes the disease at the extracellular level. Gene editing introduces new genetic material into the cells of living organisms with the intention of treating the diseases.

European regulatory framework divided gene therapy into two categories, germline gene therapy, and somatic gene therapy. In germ line gene therapy, modified genes will be passed on to next generations whereas its not the same case with somatic gene therapy. Current regulation by the EU has only allowed somatic gene therapy, therefore, germline gene therapy is banned.

The European Medical Association provides guidelines on gene therapy for preparing market authorization application to obtain approval from the authority to carry on research and development activities in gene therapy. For instance, the EU provides guidance note on gene therapy medicinal product which is intended for use in humans, defines scientific principles and provide guidance for development and evaluation of gene therapy products.

Key Topics Covered:

1. Executive Summary

2. Gene Editing Market Characteristics

3. Gene Editing Market Trends and Strategies

4. Impact Of COVID-19 On Gene Editing

5. Gene Editing Market Size and Growth

5.1. Global Gene Editing Historic Market, 2015-2020, $ Billion

5.1.1. Drivers Of the Market

5.1.2. Restraints On the Market

5.2. Global Gene Editing Forecast Market, 2020-2025F, 2030F, $ Billion

5.2.1. Drivers Of the Market

5.2.2. Restraints On the Market

6. Gene Editing Market Segmentation

6.1. Global Gene Editing Market, Segmentation by Technology, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.2. Global Gene Editing Market, Segmentation by End Users, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.3. Global Gene Editing Market, Segmentation by Application, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7. Gene Editing Market Regional and Country Analysis

7.1. Global Gene Editing Market, Split by Region, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7.2. Global Gene Editing Market, Split by Country, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/ns9rjy

with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

More here:

Global Gene Editing Market Research Report 2021 Featuring CRISPR, GenScript, Horizon Discovery Group, Integrated DNA Technologies and New England...

The carbon nanotube device could streamline some cancer therapies like CAR T-cell therapy.

Researchers at the University of Rochester Del Monte Institute for Neuroscience and Rochester Institute of Technology have received a U.S. patent for technology designed to accelerate development of cell therapies for cancer and other bio-therapies. The technique provides a less toxic alternative to standard gene transfer techniques by using an array of carbon nanotubes to deliver DNA into primary neurons, immune cells, and stem cells.

Our goal is to provide a technology that can lower the cost and increase speed and the range of cell types that can be adapted for therapeutic use, said Ian Dickerson, Ph.D., associate professor of Neuroscience. Many new cell-based therapies depend on changing the gene expression of primary cells. These approaches range from stem cells for production of patient-specific repair tissues, to CAR T-cells used for focused cancer therapy.

Dickerson and Michael Schrlau, Ph.D., associate professor of mechanical engineering in RITs Kate Gleason College of Engineering, were recently awarded a patent for this technology. It delivers biomolecules into cells through carbon nanotube arrays. Their honeycomb of nanotubes device was first described in a 2016 study published in the journal Small.

A scanning electron micrograph (SEM) of a macrophage cell sitting on top of the bed of carbon nanotubes.

The carbon nanotubes aim to be an alternative to conventional gene transfer methods that have a number of limitations including expensive equipment, low efficiency, and results in high toxicity that damages the cells. These methods limit the types of experiments that can be done and many cells like stem cells, primary cells, and immune T-cells. With Dickersons and Schrlaus device cells are able to grow on the carbon nanotube, genes are then transferred through the tubes and taken up by the cells through endocytosis. It has been successful at culturing a number of cell types, including immune cells, stem cells, and neurons, all are typically difficult to grow and keep alive.

The initial research that lead to this device was supported in part by a $50-thousand SchmittProgram in Integrative Neuroscience pilot award from the Del Monte Institute for Neuroscience. It funded Dickersons project entitled High Efficiency Injection of Biomolecules into Uticle Cells by Carbon Nanotube Arrays. This funding enabled us to begin manufacturing these carbon nanotube devices, and test the function on cell lines, which provided preliminary data that proved the concept of carbon nanotube-mediated gene transfer would work, said Dickerson.

The researchers are now collaborating with investigators at Wilmot Cancer Institute to further explore using this device for cancer therapies like CAR T-cells. "Currently CART-cells are manufactured using a viral vector to accomplish gene transfer, said Patrick Reagan, M.D., assistant professor of Medicine at the Wilmot Cancer Institute.Gene transfer via carbon nanotubules represents a novel method of gene transfer that could make the manufacturingprocess more efficient. This is important given that many of the patients treated with CAR T-cell therapy for lymphoma and leukemia have aggressive disease and the time delays associated with CAR T-cell manufacturing can lead to adverse outcomes."

See the original post:

URMC & RIT faculty awarded patent for gene transfer technology that could transform cancer therapies - URMC

The CGT Catapult was established to advance the growth of cell and gene therapies in the UK by bridging the gap between scientific research and full-scale commercialisation. As it prepares to open a new facility in the Edinburgh BioQuarter next summer, we put questions to its chief clinical officer Dr Jacqueline Barry.

How effective a bridge between academia and industry has CGT Catapult been?

When we were set up in 2012, there wasnt really a strong cell and gene therapy (CGT) industry. The UK is now the largest cluster for cell and gene therapies outside the United States. About 30 per cent of all CGT companies in Europe are in the UK, and the UK has representation in 12 per cent of global clinical trials. So were now becoming quite a mature industry, and the UK is known and respected globally for advanced therapies.

Our role is to create powerful collaborations which overcome challenges to the advancement of the sector. Id say weve done pretty well in bridging the gap between industry and academia, including creating new collaborations, supporting the creation of spin-out from universities and facilitating progress of companies towards commercialisation.

We continue to focus on this as a core activity for Cell and Gene Therapy Catapult.

What areas of academic need was CGT Catapult able to address?

It depends who the academics are. Some have already spun-out successful companies like Autolus Therapeutics, which announced a $250 million investment by Blackstone this month.

Another is Resolution Therapeutics, founded from a collaboration between Edinburghs Centre for Regenerative Medicine, the Scottish National Blood Transfusion Service, and Syncona Investment Management.

The company is based in the Centre for Regenerative Medicine on the Edinburgh Royal Infirmary campus. A further example would be Purespring Therapeutics, a spin-out from the University of Bristol, which secured one of the largest single investments to date for a new UK university biotech company.

While others are still relatively early in their product development path, we can use our facilities and expertise to accelerate them through the translation pathway.

We provide support through collaborative grants, for example, support of the design of a non-clinical testing programme, and provide commercialisation of research support for really promising technology or therapies to help them secure investment for their research.

How was CGT Catapult able to help industry to bring therapies closer to the market?

We try to anticipate barriers and then act to break them down. For example, a number of years ago we identified there wasnt enough cleanroom manufacturing space for late-stage clinical trials and early market release. In response to this barrier, we established our Manufacturing Innovation Centre in Stevenage, 30 miles north of London. This is a unique collaborative model, where we provide the support in the form of facility licensure, quality and warehouse management systems, environmental monitoring etc, while our collaborators can develop their processes and expertise within their own manufacturing module using their staff and processes.

Our collaborators having such space to build expertise and in-house knowledge is really valuable for them, and it cements their ability to manufacture and supply here in the UK.

In addition, we help with projects 100+ a year of different sizes and complexity, providing technology and process innovation solutions, or helping groups navigate the regulatory and reimbursement challenges and barriers.

How has CGT Catapult helped to foster a culture of innovation?

Innovation can mean so many different things. Technology and process innovation is important, and we help groups with process and analytical solutions. For example, weve taken processes with say 1,000 manual steps and automated the manufacture, increasing the security of the product.

Another could be in the clinical space. The Industrial Strategy Challenge Fund made funds available for the Advanced Therapy Treatment Centre network. This is truly innovative. Were working with 65 industry partners alongside the NHS to come up with solutions for these innovative but disruptive products for patients. Working hand-in-hand with industry and the NHS, we are innovating together, producing practical solutions for both parties.

What are the challenges for the NHS with these kinds of products?

These are living therapies, its disruptive and difficult to deliver these products. In addition, there is an avalanche of products coming with different product types for different indications and different patient groups.

Specialists might not be familiar with these new products. There are often complex referral pathways, so theyre only delivered from particular hospitals. There are specific regulatory and reimbursement conditions placed on the manufacturers. All these things together add complexity and require innovative solutions to not increase the burden for the NHS.

The CGT Catapult aims to help cell and gene therapies to be safer, more effective, scalable and affordable. How do you maintain research integrity and best practice in the face of that constant demand to do things better, faster, cheaper?

Were all scientists and we know this is a young field which has great promise. I think its just in everybodys DNA to ensure that your data integrity is as solid as it possibly can be.

These are quite unusual products which are designed to treat patients who are either at the end of their treatment regimen for example, treatment of a blood cancer or for the treatment of rare genetic disorders, and you want to catch their symptoms before they start impacting on their day-to-day life. So you have to act quickly, but be really confident that your data supports the use of these products.

Why is CGT Catapult coming to Edinburgh [in summer 2022]? Whats it adding?

A lot of cell and gene therapy work is currently focused in southern England, where we have also seen the third-largest cell and gene therapy cluster developing around Stevenage. There are, however, opportunities for growth and further cluster development across the UK, creating jobs and offering equity of access for patients through the UK.

The CGT Catapult will have offices and labs based in the Institute for Regeneration and Repair in the Bioquarter, Edinburgh. The University of Edinburgh and Scottish Blood Transfusion Service have considerable expertise in the development of cell and gene therapy products. Between the Scottish Centre for Regenerative Medicine and the Institute for Regeneration and Repair [currently under construction in the BioQuarter], the University of Edinburgh will have 500 stem cell scientists. Thats the biggest accumulation of stem cell scientists in Europe, and possibly the world.

Pluripotent stem cells [cells with the capacity to develop into all cell types] offer new possibilities for off-the-shelf products. The Cell and Gene Therapy Catapult will work with these scientists to develop their products and accelerate them through clinical trials and become investable propositions, whether through spin-out companies or investment by big pharma.

In addition, we want to work with the NHS, academics, industry and the whole life sciences community to make the best potential of the wealth of experience in the Central Belt of Scotland and use it for the advantage for all of the UK.

Whats the future vision for CGT Catapult?

Our vision is a thriving industry delivering life changing advanced therapies to the world. For the UK to remain one of the most important players globally for these advanced cell and gene therapies.

We want the UK to be at the forefront of manufacture and supply of these living therapies. We want our NHS to be able to adopt them quickly and ensure they get to the right patients as quickly as possible. The UK, thanks to its favourable ecosystem including CGT Catapults activities and continued impact on it, and the continuous support by government for innovation, can stay at the forefront of that.

View post:

Bridging the cell and gene therapy gap - The Scotsman

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today reported topline efficacy and safety results at 2 years post-treatment administration in the REFLECT Phase III clinical trial with LUMEVOQ. The results show sustained efficacy and safety for bilateral intravitreal injection of the gene therapy, including better efficacy compared to unilateral injection.

The findings reinforce the results observed at 1.5 years post-treatment administration, which were reported in June 2021.

The REFLECT trials demonstration of a sustained, significant and safe improvement in visual acuity for LHON patients treated bilaterally with LUMEVOQ provides additional impetus for our push to gain regulatory approval, said Bernard Gilly, CEO and Co-Founder of GenSight Biologics. Patients afflicted with LHON who are losing their sight deserve access to a treatment like LUMEVOQ.

Designed under a Special Protocol Assessment with the FDA, REFLECT is a randomized, double-masked, placebo-controlled Phase III trial involving 98 subjects with vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene; enrolled ND4 subjects had vision loss up to one year from onset. The ND4 mitochondrial mutation is associated with the most severe clinical form of LHON, with poor overall visual outcomes.1 All subjects received an intravitreal injection (IVT) of LUMEVOQ in their first affected eye. The second affected eye was randomized to either a second IVT of LUMEVOQ or a placebo IVT, which was administered on the same day or the following day. 48 subjects were randomized to LUMEVOQ bilateral treatment, and 50 to LUMEVOQ unilateral treatment (first-affected eye treated with LUMEVOQ, second-affected eye treated with placebo).

Significant visual acuity improvement over baseline, with better results for bilaterally injected patients

Two years after injection, the mean best-corrected visual acuity (BCVA) in LUMEVOQ-treated eyes was statistically significantly better than baseline, whereas the improvement from baseline was not statistically significant in placebo-treated eyes. The results indicate a sustained treatment effect for all subjects, with the improvement being greater among bilaterally treated patients.

Table 1: Change in Best-Corrected Visual Acuity (BCVA) versus Baseline, 2 Years after Injection

1st affected eye

2nd affected eye

Subjects bilaterallyinjected with LUMEVOQ

LUMEVOQ-0.25 LogMAR+13 ETDRS lettersp=0.0006

LUMEVOQ-0.18 LogMAR+9 ETDRS lettersp=0.01

Subjects unilaterallyinjected with LUMEVOQ

LUMEVOQ-0.16 LogMAR+8 ETDRS lettersp=0.02

PLACEBO-0.10 LogMAR+5 ETDRS lettersp=0.1 (NS)

The contralateral effect observed with placebo at 2 years is consistent with that which was documented in sham-treated eyes in the REVERSE2 and RESCUE3 trials.

Year 2 analyses also confirm the dose effect that was noted at Year 1.5: the mean BCVA at 2 years for bilaterally and unilaterally treated subjects reached 1.32 and 1.44 LogMAR, respectively, with an absolute difference between arms of +6 ETDRS letters in favor of bilaterally treated subjects.

Responder analyses point to the benefits of treatment for patients that would otherwise have experienced significant vision loss with a very low likelihood of spontaneous recovery.1 For example, 60% of the bilaterally treated patients (56% of unilaterally treated patients) who had vision above the threshold of legal blindness in at least one eye remained above the threshold at Year 2.

Efficacy demonstrated even more clearly in visual acuity improvement from nadir

Comparison against nadir (i.e., the worst BCVA recorded from baseline to Year 2) more starkly demonstrates the efficacy of LUMEVOQ, even for the placebo eyes that improved via a contralateral treatment effect.

Table 2: Change in Best-Corrected Visual Acuity (BCVA) versus Nadir, 2 Years after Injection

1st affected eye

2nd affected eye

Subjects bilaterallyinjected with LUMEVOQ

LUMEVOQ-0.39 LogMAR+20 ETDRS lettersp<0.0001

LUMEVOQ-0.34 LogMAR+17 ETDRS lettersp<0.0001

Subjects unilaterallyinjected with LUMEVOQ

LUMEVOQ-0.38 LogMAR+19 ETDRS lettersp<0.0001

PLACEBO-0.27 LogMAR+14 ETDRS lettersp<0.0001

Responder analyses indicate that the treatment effect is not limited to just a minority of subjects. Two years after injection, 73% of bilaterally treated subjects and 66% of unilaterally treated subjects had experienced a clinically meaningful improvement of at least -0.3 LogMAR (+15 ETDRS letters) relative to their observed nadir.

Table 3: Responder Analyses, Based on Change from Nadir at Year 2

Definition of Responder

-0.3 LogMAR improvement inat least one eye

Clinically Relevant Recovery*in at least one eye

Subjects bilaterallyinjected with LUMEVOQ

73%

75%

Subjects unilaterallyinjected with LUMEVOQ

66%

60%

Note: *Clinically Relevant Recovery is defined as: i) For eyes on-chart at nadir, an improvement of -0.2 LogMAR (10 ETDRS letters) from nadir; or ii) For eyes off-chart at nadir, eyes which became on-chart (i.e., BCVA 1.6 LogMAR).

Bilateral injections have a favorable safety profile

The favorable safety profile of LUMEVOQ was confirmed. There was no study discontinuation related to systemic or ocular adverse events, and there were no serious ocular adverse events. The main ocular adverse event was intraocular inflammation, which was mostly mild and responsive to conventional treatment. The favorable safety profile was comparable in unilaterally and bilaterally treated subjects.

The persistence of LUMEVOQ efficacy is remarkably consistent across the development program, so that the REFLECT results bolster the evidence provided by 3 years of data from RESTORE4 and 5 years of data from REVEAL, noted Magali Taiel, MD, Chief Medical Officer of GenSight Biologics.

Results of the 4-year follow-up of RESTORE are expected to be available in January 2022.

Dr. Taiel added, Moreover, we affirm the insight that bilateral injection of LUMEVOQ is the best option for patients with ND4 Leber Hereditary Optic Neuropathy.

REFLECT patients have been invited to participate in a long-term follow-up that will monitor the safety and efficacy of LUMEVOQ up to 5 years post-injection.

References:

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in subjects suffering from blinding retinal diseases. GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer subjects a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 1,200-1,500 new subjects who lose their sight every year in the United States and the European Union.

About LUMEVOQ (GS010; lenadogene nolparvovec)

LUMEVOQ (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. LUMEVOQ was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018.

About REFLECT

REFLECT is a multi-center, randomized, double-masked, placebo-controlled study to evaluate the safety and efficacy of bilateral injections of GS010 in subjects with LHON due to the NADH dehydrogenase 4 (ND4) mutation. In the active arm, GS010 was administered as a single intravitreal injection in each eye of each subject. In the placebo arm, GS010 was administered as a single intravitreal injection to the first affected eye, while the fellow eye received a placebo injection.

The primary endpoint for the REFLECT trial is the BCVA reported in LogMAR at 1.5 years (78 weeks) post-treatment in the second-affected/not-yet-affected eye. The change from baseline in second-affected/not-yet-affected eyes receiving GS010 and placebo is the primary response of interest. The secondary efficacy endpoints include: BCVA reported in LogMAR at 2 years post-treatment in the second-affected/not-yet-affected eye compared to both placebo and the first-affected eye receiving GS010, OCT and contrast sensitivity and quality of life scales.

The trial was conducted in multiple centers across Europe (1 each in France, Spain, Italy and the UK), the US (6 centers) and Taiwan (1 center). The trial planned to enroll 90 subjects with vision loss up to 1 year in duration; 98 subjects were successfully screened and treated. The first subject was treated in March 2018 and the last one in July 2019.

ClinicalTrials.gov Identifiers:REFLECT: NCT03293524

See the original post here:

GenSight Biologics Confirms Sustained Efficacy and Safety of Bilateral LUMEVOQ Injections at 2-Year Follow-Up of REFLECT Phase III Trial - Business...

A group of gene therapy experts called for better research tools and more careful monitoring of side effects to treatment, but stopped short in a high-profile meeting Thursday of advocating for major changes to how studies in the fast-growing field are conducted.

The committee, which the Food and Drug Administration convened for advice on the risks to gene therapy, proposed a number of ways research could potentially be made safer, such as by improving how patients are screened for clinical trials. None of the panel members, though, suggested slowing research in any significant fashion, rejecting, for instance, the idea of imposing an upper limit on gene therapy doses to lower risks.

"While the meeting was an excellent update on pre-clinical and clinical adverse events in the field, it largely left untouched what measures might actually be taken to help future-proof this field," said Anthony Davies, founder and CEO of Dark Horse Consulting, which specializes in gene therapy.

Experts said that inconsistent standards in how gene therapies are produced, and how certain safety risks are assessed, made it difficult to come up with recommendations that could be broadly applied.

The meeting, which will continue Friday, comes after a series of safety incidents in gene therapy clinical trials resurfaced some longstanding concerns, as well as new worries about the use of high treatment doses. The deaths last year of three children in a study of a neuromuscular disease therapy, in particular, appear to have spurred the FDA to seek the experts' advice.

"Our enthusiasm for this field must be balanced by caution," said Wilson Bryan, director of the FDA's Office of Tissues and Advanced Therapies, in a presentation opening the meeting Thursday. "The greatest risks in drug development fall on the patients who receive an investigational product."

The FDA split the first day of the meeting into two sessions, focusing the first on the persistent worry that injecting genes into cells might eventually spur cancer, and the second on the liver injury that can be caused by treatment. The committee will discuss brain toxicity Friday.

In discussing the risk of cancer, experts spent considerable time weighing findings from testing in animals, some of which dates back more than 20 years. Results have shown that a commonly used delivery tool, the adeno-associated virus or AAV, can fuse itself into the genomes of certain animals and, at least in mice, that integration is associated with liver cancer.

Concerns around whether this risk can play out similarly in humans grew earlier this year when a patient given an experimental hemophilia gene therapy developed by the biotech company UniQure was diagnosed with liver cancer.

UniQure has since exonerated its gene therapy, and experts at the FDA panel noted the risk remains theoretical. Other research in larger animals and in humans haven't replicated the worrisome findings in mice. A study following dogs given a hemophilia gene therapy and presented at the meeting by University of Pennsylvania researcher Denise Sabatino, for example, showed AAV did get into the genome but didn't lead to cancer.

"[T]his is something that will need to be monitored very carefully, [but] so far, the signal in the clinic doesn't seem to be very strong," said Christopher Breuer, the director of the center for regenerative medicine at Nationwide Children's Hospital, a top gene therapy hub.

Pfizer, which has invested heavily in gene therapy, argued companies shouldn't have to run more studies looking for integration events in animals until there is "clear causality in humans," according to a public comment filed with the FDA. Pfizer claimed additional experiments using human cell lines to assess risk would be more relevant.

FDA panelists, meanwhile, said longer animal tests might more effectively capture any cancer risk of AAV, as will tracking the health of the more than 800 children who have so far received the Novartis spinal muscular atrophy treatment Zolgensma. Experts also suggested closer scrutiny of gene therapy components.

But several were hesitant to make broad recommendations to the FDA as there aren't set rules for every aspect of how gene therapies are made.

"We are starting to get a sense of the scientific issues that are out there, but we need to start to drive towards some type of standardization," said Taby Ahsan, the head of biologics analytical development at MD Anderson Cancer Center. "Understanding that will help us give solid recommendations for preclinical study design as we move forward."

While the cancer risk of AAV gene therapy in humans remains theoretical, liver toxicity is one of the most common side effects reported in clinical testing to date and, in a few cases, has led to serious health problems.

In a study of a gene therapy developed by Audentes Therapeutics, for instance, three young children given a very high dose developed liver damage and later died, although the exact link between their deaths and the treatment is still unclear. Two cases of acute liver failure have also been reported in patients treated with Zolgensma, and many hemophilia patients across several gene therapy studies have experienced significant increases in liver enzyme counts, a potentially worrisome sign.

"I think that a lot of the studies have missed opportunities to involve hepatologists early on," said Theo Heller, a liver specialist at the National Institute of Diabetes and Digestive and Kidney Diseases, at the meeting. "Hepatotoxicity is such a common side effect of this therapy."

Experts did call on researchers to more comprehensively assess and screen for preexisting liver conditions, which they said might affect how side effects develop.

"We do need careful screening," said Lisa Butterfield, the meeting's chair and vice president of the Parker Institute for Cancer Immunotherapy at the University of California, San Francisco. "We need to focus on more than just fluctuations in blood work."

The committee made few other concrete recommendations on how best to manage the risk of liver problems, though. In particular, they opposed placing an upper limit on the gene therapy doses that could be tested, although research suggests the worst health consequences to liver toxicity only emerge at higher doses.

A major sticking point, some members noted, was the difficulty in characterizing the make-up of gene therapy doses, which can contain extraneous material alongside the therapeutic DNA.

"It confounds this question of toxicity and toxic side effects of AAV perhaps because, again, going back, we don't have reference standards for the field," said Charles Venditti, a senior investigator with the National Human Genome Research Institute.

Read more:

At FDA meeting, gene therapy experts wrestle with field's blindspots - BioPharma Dive

Joe Rogan, who hosts one of the most popular podcasts on Spotify, wrongly claimed that the Pfizer and Moderna COVID-19 vaccines are "really gene therapy," conflating the vaccines pioneering mRNA technology with the experimental technique that involves modifying genes to treat or cure disease.

The inaccurate claim came about 51 minutes into the Aug. 20 episode of "The Joe Rogan Experience" as Rogan discussed the vaccines with guest Meghan Murphy, a Canadian freelance writer and journalist.

Heres what Rogan said:

"It's not really a vaccine in the traditional sense. A vaccine is where they take a dead virus, and they turn it into a vaccine, and they inject it into your body so that your body fights off it develops the antibodies, and your body understands what that is, whether it's the measles or polio, it knows how to fight it off.

"This is really gene therapy. It's a different thing. Its tricking your body into producing spike protein and making these antibodies for COVID. But its only good for a few months, theyre finding out now. The efficacy wanes after five or six months. Im not saying that people shouldnt take it. But Im saying, youre calling it a thing that its not. Its not exactly what youre saying it is, and youre mandating people take it."

Theres no national mandate requiring that all Americans get vaccinated against COVID-19, although many employers and university systems are requiring it. And Rogan based his claim about the COVID-19 vaccines partly on an outdated conception of what a vaccine is.

But the bigger problem with the claim is that it mischaracterizes the technology used by the Pfizer and Moderna vaccines. The technology does not amount to gene therapy, public health experts said.

"It's absolutely incorrect to say that vaccines are really gene therapy," said Cindy Prins, clinical associate professor of epidemiology at the University of Florida. "Vaccines don't make any changes to your own DNA, so they don't edit your own DNA like gene therapy does. They also don't replace any mutated genes in your body."

No genetic material enters the part of the cell that hosts DNA as a result of the mRNA vaccines.

Rogan and Spotify did not offer on-the-record comments for this fact-check.

How the mRNA COVID-19 vaccines work

The Centers for Disease Control and Prevention defines a vaccine as "a product that stimulates a persons immune system to produce immunity to a specific disease."

"Basically, a vaccine is a way to get your immune system to recognize something and create antibodies to it," said Richard Watanabe, professor of population and public health sciences at the University of Southern California.

The Pfizer and Moderna vaccines fit that definition, the CDC says. While they work differently than many other familiar vaccines relying on messenger RNA, or mRNA, technology they still trigger an immune response inside the body, offering vital protection.

Older methods of vaccination included inoculating people with inactivated versions of viruses, and some vaccines for other diseases still work that way. But that method has proven at times to be risky, Watanabe said, citing the infamous "Cutter Incident" of 1955, in which some polio vaccines were not properly inactivated and tens of thousands of people were accidentally injected with the live virus.

The mRNA technology in the Pfizer and Moderna COVID-19 vaccines is newer, though research on it dates back to the 1990s.

The vaccines work by instructing the cells to make versions of a harmless spike protein found on the surface of the coronavirus, so the immune system can recognize the protein and mount an antibody response against the virus in the event of a future infection, the CDC says.

The third COVID-19 vaccine available in the U.S., from Johnson & Johnson, delivers similar instructions using an adenovirus thats been altered to make it harmless.

"Its true that mRNA vaccines are a major departure from traditional vaccines," said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security. "They contain just the genetic material of the gene of interest in the pathogen that codes for the protein needed for immunity. Thats what makes them so path-breaking."

The mRNA vaccine technology isnt really gene therapy

While both mRNA vaccination and gene therapy involve genetic technology, they are different things, experts said.

Gene therapy involves modifying a persons genes to cure or treat a disease, according to the Food and Drug Administration. The FDA says it can work by replacing a disease-causing gene in the body with a healthy version, turning off the disease-causing gene, or introducing a new gene entirely. Only a few gene therapies have been fully approved, said Prins.

"Gene therapy is used to replace or fix genetic mutations that lead to diseases like cystic fibrosis, neuromuscular disease, inherited blindness and other genetic conditions," Prins said. "Gene therapy is not used in vaccines at all, since vaccines don't replace or edit your own genes."

Gene therapy corrects a genetic defect by delivering the gene, or DNA, to the nucleus, the part of the cell where DNA is located, Adalja said.

The mRNACOVID-19 vaccines are designed around the genetic structure of the virus. They carry mRNA, which teaches the immune system to identify the coronavirus, but they do not alter the recipients genetic makeup or DNA. The mRNA strands never enter the nucleus of the cell after vaccination.

To cross into the nucleus, the mRNA chains from the shots would need a special enzyme, according to WebMD. And they would need another enzyme to be integrated into the DNA. They dont have those enzymes.

"Its really just a different approach to delivering what the immune system needs to see in order to create the antibodies," Watanabe said of the mRNA vaccines.

The mRNA strands also break down shortly after entering the body, unlike with gene therapy, Prins said.

"It sticks around in the cell only long enough to be used as a recipe to make some spike protein that the immune system can then detect and respond to," Prins said. "After a few days, your cells will break up that mRNA into small pieces. So the recipe gets torn up. The spike protein that was made will stay around a little longer, up to a few weeks, which helps you build that immune response. But it will also get broken down so it doesn't stay for long."

Moderna says on its website that while mRNA and gene therapy might sound similar, they "take fundamentally different approaches." The company wrote:

"Gene therapy and gene editing alter the original genetic information each cell carries. The goal is to produce a permanent fix to the underlying genetic problem by changing the defective gene ... Unlike gene editing and gene therapy, mRNA technology does not change the genetic information of the cell, and is intended to be short-acting."

In the same podcast episode, Rogan claimed that "its not supported by science" for people who have previously been sick with COVID-19 to get the shots. But public health experts recommend that people who have had COVID-19 already get immunized anyway, because the science shows they provide better and broader protection than natural immunity.

Our ruling

Rogan said the mRNA COVID-19 vaccines are "really gene therapy."

Thats wrong. The two interventions are not the same. Gene therapy involves modifying genes to cure or treat a disease.

The COVID-19 vaccines from Pfizer and Moderna use mRNA technology to instruct the cells to recognize a spike protein on the coronavirus and mount a response against it, but they make no changes to the recipients genetic makeup or DNA. The mRNA strands never enter the part of the cell that hosts DNA, and they are broken down soon after they are introduced into the body.

We rate Rogans claim False.

RELATED: Spotifys Joe Rogan repeats inaccurate claim that they are monitoring SMS texts

RELATED: Youth is not invincible: 9 experts dispute Joe Rogans vaccine advice for healthy 21-year-olds

Continued here:

Joe Rogan falsely says mRNA vaccines are 'gene therapy' - PolitiFact

Dive Brief:

Most gene therapies currently in development use small viruses called AAVs, or adeno-associated viruses, to shuttle helpful genetic material into human cells.

When given intravenously, as is usually the case, these AAV-based therapies travel straight to the liver, where they're then processed. The liver therefore acts as a window into how patients respond to treatment with gene therapy, and provides alerts when problems may arise.

Indeed, liver toxicity, often diagnosed by elevated enzyme levels but sometimes by damage to the organ,is the most common adverse event in clinical trials testing intravenously administered AAV vectors. And though toxicity can be managed, some cases are serious enough that they require longer care or even hospitalization.

In one example cited by the FDA, certain patients treated with Zolgensma, the Novartis gene therapy for spinal muscular atrophy, needed corticosteroids for more than seven months to deal with liver toxicity issues. According to the agency, among the roughly 800 patients who've received Zolgensma thus far, about a third have experienced at least one instance of liver toxicity.

Liver toxicity has also come into focus for AAV gene therapies targeting hemophilia, as well as for the one Astellas is developing. The safety concerns are significant enough that, later this week, the FDA is convening a group of gene therapy experts to assess the risks involved when using AAV vectors for gene therapy.

For Astellas, a voluntary pause on screening and dosing is another hard-felt setback.

So far, the AT132 trial has administered the therapy to 24 patients, with seven on the lower dose and 17 on the higher. Three participants on the higher dose developed a progressive form of hepatitis that led to liver failure. Those patients later died from either sepsis or gastrointestinal bleeding as a result of the liver failure.

One patient on the lower dose has now experienced liver problems too. Astellas said in a statement Wednesday that the patient, like some others with X-linked myotubularmyopathy, has a history of intermittent cholestasis, a condition which disrupts the flow of bile from the liver.

The company noted, though, that before receiving AT132, the patient had a "normal" liver ultrasound and liver function test results which met the trial's eligibility criteria.

Astellas said it will be closely monitoring the patient and, if the FDA ultimately issues a clinical hold, it will "review the content and determine next steps."

"As we learn more about the case, we will incorporate any new observations into our ongoing investigation in order to have a well-informed discussion with the independent Data Monitoring Committee, our Liver Advisory Panel, and study investigators," said Nathan Bachtell, head of gene therapy, medical and development at Astellas.

"Given previous hepatic events within the program, any one [serious adverse event] needs to be viewed both individually and in the context of the broader program as we move forward," Bachtell added.

Astellas acquired AT132 through its $3 billion acquisition of Audentes Therapeutics, which has since been rebranded as an independent subsidiary named "AstellasGene Therapies." Amid this transition, the former chief executive at Audentes,Natalie Holles,left the combined company in April for undisclosed reasons.

Astellas is also working on other gene therapies for Pompe disease, Duchenne muscular dystrophy and myotonic dystrophy type 1.

Read the original post:

Astellas again hits pause on gene therapy trial - BioPharma Dive

Posted: Sep 3, 2021 / 11:14 AM EDT / Updated: Sep 3, 2021 / 11:14 AM EDT

HARTFORD, Conn., (WTNH) Connecticut Childrens announced that it is now the first hospital in the state to be in contract with Cignas Gene Therapy Program on Friday.

The Cigna Gene Therapy Program will give covered families have immediate access to the therapy, and have affordable options for previously expensive gene therapy medication.

Families covered by Cigna can more want gene therapy for children with spinal muscular atrophy while avoiding $2 million worth of medicine. According to Cignas website, the provided medicine will be available to covered families for less than $1 a month.

Connecticut Childrens is committed to finding innovative treatments for devastating diseases, but at a price that wont bankrupt families, said Jim Shmerling, DHA, FACHE, President & CEO of Connecticut Childrens. We have an obligation to all children to ensure they can access to the specialists and cutting edge treatments they need at all times.

Expensive therapies for rare diseases are posing a challenge for healthcare. As shown in reports, many families have to make difficult decisions in order to pay for the necessary medicine. EvaluatePharma research shows that by 2024, the cost of gene therapy in the U.S. will be over $16 billion.

As drug prices continue to climb, we have an obligation to work for our patients and families and continue advocating on their behalf to the insurance companies and lawmakers, said Shmerling. All children deserve access to these kinds of therapies.

Read the original here:

Connecticuts Children first to enroll affordable gene therapy - WTNH.com

SAN FRANCISCO, Sept. 1, 2021 /PRNewswire/ --The global cell and gene therapy manufacturing marketsize is expected to reach USD 57.4 billion by 2028, according to a new report by Grand View Research, Inc. The market is estimated to expand at a CAGR of 20.3% from 2021 to 2028. An exponential rise in clinical pipeline coupled with a rising number of regulatory approvals for advanced therapies has majorly driven the market.

Key Insights & Findings:

Read 188 page market research report, "Cell And Gene Therapy Manufacturing Market Size, Share & Trends Analysis Report By Therapy Type, By Scale (R&D, Commercial), By Mode, By Workflow (Vector Production, Cell Banking), By Region, And Segment Forecasts, 2021 - 2028", by Grand View Research

Considering promising growth opportunities in the contract development of cellular and gene-modified therapies, market participants are making focused efforts to boost their market presence. Also, bio manufacturers are signing strategic alliances with contract manufacturers to accelerate the R&D of their candidate programs. Rising demand for CMOs/CDMOs services has led to the entry of several new players as well as expansion of product development capabilities, thereby positively impacting market revenue.

Several novel methods are being introduced to advance cell and gene therapy manufacturing. For instance, the manufacturers are exploring the potential of single-use technology in production workflows. This technique is gaining increasing attention in this arena to speed the development process while reducing the overall cost and production timeline. Such technological advancements in space are anticipated to bolster market growth in the coming years.

Grand View Research has segmented the global cell and gene therapy manufacturing market on the basis of therapy type, scale, mode, workflow, and region:

List of Key Players of Cell And Gene Therapy Manufacturing Market

Check out more studies related to genetics and cell therapy, conducted by Grand View Research:

Browse through Grand View Research's coverage of the Global Biotechnology Industry.

Gain access to Grand View Compass, our BI enabled intuitive market research database of 10,000+ reports

About Grand View Research

Grand View Research, U.S.-based market research and consulting company, provides syndicated as well as customized research reports and consulting services. Registered in California and headquartered in San Francisco, the company comprises over 425 analysts and consultants, adding more than 1200 market research reports to its vast database each year. These reports offer in-depth analysis on 46 industries across 25 major countries worldwide. With the help of an interactive market intelligence platform, Grand View Research helps Fortune 500 companies and renowned academic institutes understand the global and regional business environment and gauge the opportunities that lie ahead.

Contact:

Sherry JamesCorporate Sales Specialist, USAGrand View Research, Inc.Phone: 1-415-349-0058Toll Free: 1-888-202-9519Email: [emailprotected]Web: https://www.grandviewresearch.comFollow Us: LinkedIn| Twitter

SOURCE Grand View Research India Pvt Ltd

See more here:

Cell And Gene Therapy Manufacturing Market Size Worth $57.4 Billion By 2028: Grand View Research, Inc. - PRNewswire

Season 1 of Science Will Win is a four-part miniseries exploring the science behind gene therapy; the next generation of medicines which could bring new possibilities for patients living with rare genetic diseases.

Listeners will hear from a diverse line-up of leading experts on the future-shaping science, challenging policy environment and the personal stories which remain our guiding-light in the search for breakthrough therapies of tomorrow.

At a time when innovative science is achieving the seemingly impossible, well look at gene therapy from every angle, speaking to the Pfizer scientists and experts on the forefront of medical research, as well as the patients and families who are holding new hope in the life-changing potential of gene therapy.

Subscribe and follow Science Will Win to make sure you dont miss an episode.

Season 1 of Science Will Win is hosted by Adam Rutherford, a geneticist, writer, broadcaster and Honorary Fellow at University College London (UCL), U.K. After studying evolutionary biology at UCL, Adam gained a PhD from Great Ormond St Hospital and the Institute of Child Health, London, in the genetics of the developing eye and was also part of the team that identified the first genetic cause of a form of childhood blindness. Since then, Adam spent ten years as an editor for the science journal, Nature, as well as writing and featuring in an array of BBC television, radio and podcast programmes.

Science Will Win is a podcast that takes listeners under the microscope of some the most promising medical innovations, exploring therapies which have the potential to shape the future of healthcare and offer new hope to patients around the world.

Through conversations with a diverse line-up of guests, including scientists and experts, patient advocates and, most importantly, patients themselves, each miniseries focuses on a unique healthcare challenge, diving into the fascinating science, policy challenges and potential to transform patients lives for the better.

This podcast is powered by Pfizer. The information, statements, comments, views and opinions expressed by those guests featured in this podcast are their own and not necessarily representative of the views and opinions of Pfizer Inc.

See the article here:

Science Will Win Podcast: Season 1 - Pfizer

2021 is on track to have the highest number of regulatory approvals of gene therapy and gene-modified cell therapy products. Credit: Shutterstock

To access the report and other gold-standard data, get in touch with GlobalData today.

In August 2021, the Alliance for Regenerative Medicine (ARM), in collaboration with GlobalData, published a new report highlighting that 2021 has already been a year of firsts and records for the regenerative medicine sector with significant clinical milestones, commercial progress and investment.

For example, CRISPR gene-editing technology was used for the first time in vivo, with Intellia Therapeutics announcing promising Phase I data from a clinical trial of NTLA-2001 in transthyretin (ATTR) amyloidosis patients. Using data from GlobalDatas Clinical Trial Intelligence database, the report also shows that there are over 2,600 trials for regenerative medicines ongoing worldwide, including over 1,300 industry-sponsored trials and with almost 250 in Phase III. In terms of investment, the sector raised a record $14bn in H1 2021, compared to $19.9bn for all of 2020.

In addition, 2021 is on track to have the highest number of regulatory approvals of gene therapy and gene-modified cell therapy products, with three approvals to date and four expected to get the green light by the end of the year. The report also highlights that Europe could be at risk of falling behind the US and Asia in terms of number of developers and new clinical trials.

Initiatives by ARM to educate policymakers and payers in the US and Europe on regenerative medicines are also addressed in the report. For example, ARM has assisted in shaping US policy by working with congressional sponsors on Cures 2.0 legislation and advocating for increased funding for the FDAs Center for Biologics Evaluation and Research (CBER). In Europe, ARM was involved in removing a reimbursement hurdle for hospitals in Germany that provide regenerative medicines.

To access the report and other gold-standard data, get in touch with GlobalData today.

Bespoke, Cost-Effective Preclinical Cancer Model Searches for Pharmaceutical Companies

Translation Services for Pharmaceutical and Life Sciences Companies

Bespoke, Cost-Effective Preclinical Cancer Model Searches for Pharmaceutical Companies

28 Aug 2020

Global Real Time Tracking and Monitoring Solutions for Clinical trials

28 Aug 2020

Translation Services for Pharmaceutical and Life Sciences Companies

28 Aug 2020

See original here:

Regenerative medicine 2021: report highlights record year for the sector - Clinical Trials Arena

Global Gene Therapy Market

Gene therapy is a type of experimental technique in which genes are used to treat or prevent diseases. In this therapy genes are inserted into patients cells instead of using surgery and drugs. Gene therapy has various approaches such as replacement of muted gene, inactivating or knocking out a muted gene, and introducing new gene into the body to help fight a disease.

Get Sample Copy of this Report @https://qualiketresearch.com/request-sample/Gene-Therapy-Market/request-sample

Increase in prevalence of chronic diseases like cancer is expected to boost the global gene therapy market, in this forecast period. Furthermore, rise in technological advancements in genomics and gene-editing tool will have the positive impact on gene therapy market growth. In other hand, rapid and significant progress in the molecular and cellular biology arena is expected to propel the global gene therapy market growth. Moreover, rise in product approval is expected to fuel the global gene therapy market growth.

The better understanding of the market demands a better handling of macroeconomic and microeconomic aspects that are projected to mark the progress. These factors, if guided well, can helm the target market to prosperity by wading via rough waters, all the while, keeping plummeting curves at bay. With real-time data, the Global Gene Therapy Market report is projected to provide a detailed picture of the demographic possibilities, which would assist key players in assessing growth opportunities & significantly establishing parameters which would continue to influence the market in the upcoming years.

However, high cost is the major restraining factor which is expected to hamper the global gene therapy market growth. Also, lack of skilled professionals is expected to affect the global gene therapy market growth.

Get discount on this report @https://qualiketresearch.com/request-sample/Gene-Therapy-Market/ask-for-discount

Global Gene Therapy Market Segmentation

Global Gene Therapy Market is segmented into vector type such as Viral Sector, and Nonviral Sector, by gene type such as Antigen, Cytokine, Growth Factors, Receptors, and Others. Further, Global Gene Therapy Market is segmented into application such as Oncological Disorder, Cardiovascular Diseases, Neurological Disorders, Rare Diseases, Infectious Diseases, and Others.

Also, Global Gene Therapy Market is segmented into five regions such as North America, Latin America,Europe, Asia Pacific, and Middle East and Africa.

Global Gene Therapy Market Key Players

Various key players are discussed in this report such as BIGEN, Gilead Sciences Inc., Amgen, Novartis AG, Bluebird Bio, Inc, Orchard Therapeutics Plc, Spark Therapeutics ,Human Stem cell Institutes, JAZZ Pharmaceuticals, Sibiono Genetech Co,ltd, UNIQURE N.V,Mustang Bio, and Poseida Therapeutics Inc.

The regional distribution of the Global Gene Therapy Market is also covered in the report, and detailed analysis are provided for the markets segment in each major region. The regional markets are discussed to give players clear idea of where each region is soaring & what needs attention in specific markets. Region-specific strategies as well as product formulations can be based on this detailed analysis, as the factors making the market tick in particular regions are analysed in the report, leading to a comprehensive understanding of the Global Gene Therapy Market.

Browse Full Research Report @https://qualiketresearch.com/reports-details/Gene-Therapy-Market

About Us

QualiKet Research is a leading Market Research and Competitive Intelligence partner helping leaders across the world to develop robust strategy and stay ahead for evolution by providing actionable insights about ever changing market scenario, competition and customers. QualiKet Research is dedicated to enhancing the ability of faster decision making by providing timely and scalable intelligence. We use different intelligence tools to come up with evidence that showcases the threats and opportunities which helps our clients outperform their competition.

Contact Person:

Vishal Thakur

Research Support Specialist

QualiKet Research

6060 N Central Expy #500, TX 75204, U.S.A

Email: sales@qualiketresearch.com

Website: https://qualiketresearch.com

Read the rest here:

Global Gene Therapy Market Top Companies, Size, Growth Analysis, Segmentation, Industry Outlook Analysis , and Forecast 2020 to 2027 UNLV The Rebel...

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Paris:SIGHT)(Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the Journal of Neuro-Ophthalmology (JNO) has published results from RESTORE, the long-term follow-up study of LUMEVOQ, which show sustained treatment effect from a unilateral injection of LUMEVOQ three years after injection in the RESCUE and REVERSE trials.

The paper*, published in the September issue of JNO under the title Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study, presents analyses that show sustained improvement in best-corrected visual acuity (BCVA) and quality of life scores three years after subjects received LUMEVOQ treatment. The continuous improvement in BCVA was demonstrated in both eyes of the unilaterally treated patients, confirming the contralateral treatment effect reported in the RESCUE and REVERSE trials.

It is gratifying to see this sustained outcome, commented lead author Dr. Valrie Biousse, MD, Departments of Ophthalmology and Neurology, Emory University School of Medicine, Atlanta, GA. Dr. Biousse, who was also an coinvestigator in the RESCUE and REVERSE trials, added, This is further evidence of a bilateral therapeutic effect of a single unilateral gene therapy injection.

Mean BCVA steadily improved to 1.26 LogMAR at 48 months after onset (3 year-post injection), remaining onchart (i.e., better than 1.6 LogMAR) throughout the follow-up period. A locally-estimated scatterplot smoothing (LOESS) regression analysis illustrates the progressive and sustained improvement of BCVA in RESTORE subjects (Figure 1) since treatment with LUMEVOQ.

In addition, subjects quality of life continued to improve between Year 2 and Year 3 post-injection, as documented by scores reported in the visual function questionnaire VFQ-25. Relative to baseline, the mean VFQ-25 composite score (averaging 11 visionrelated subscales) was higher by 4 points at Year 2 and 7 points at Year 3. At Year 3, clinically meaningful improvement from baseline were seen in the sub-scores that corresponded to mental health (+21 points), role difficulties (+17 points), dependency (+15 points), general vision (+9 points), near activities (+6 points), and distance activities (+5 points).

RESCUE and REVERSE were randomized, double-masked, sham-controlled, Phase III clinical trials that assessed the efficacy and safety of LUMEVOQ gene therapy as a treatment for vision loss due to ND4-LHON. The only difference between the two studies was the duration of vision loss at screening: RESCUE subjects had vision loss for less than 6 months, while REVERSE subjects had vision loss for 6 to 12 months. The 72 subjects who completed the Phase III trials RESCUE and REVERSE were invited to participate in RESTORE, and 62 (86.1%) agreed to be monitored up to five years after treatment.

The paper is available at: https://journals.lww.com/jneuro-ophthalmology/Fulltext/2021/09000/Long_Term_Follow_Up_After_Unilateral_Intravitreal.5.aspx.

*About the paper:

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study

Authors: Valrie Biousse, MD1, Nancy J. Newman, MD1, Patrick Yu-Wai-Man, MD, PhD2,3,4,5, Valerio Carelli, MD PhD6,7 , Mark L. Moster, MD8, Catherine Vignal-Clermont, MD9,10, Thomas Klopstock, MD11,12,13, Alfredo A. Sadun, MD, PhD14, Robert C. Sergott, MD8, Rabih Hage, MD10, Simona Esposti, MD4, Chiara La Morgia, MD, PhD6,7, Claudia Priglinger, MD15, Rustum Karanja, MD, PhD14,16, Laure Blouin, MSc17, Magali Taiel, MD17, Jos-Alain Sahel, MD, PhD10,18,19,20 for the LHON Study Group

Affiliations:

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of patients have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 800-1,200 new patients who lose their sight every year in the United States and the European Union.

About LUMEVOQ (GS010; lenadogene nolparvovec)

LUMEVOQ (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. LUMEVOQ was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018.

About RESCUE, REVERSE, and RESTORE

RESCUE and REVERSE were two separate randomized, double-masked, sham-controlled Phase III trials designed to evaluate the efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in subjects affected by LHON due to the G11778A mutation in the mitochondrial ND4 gene.

The primary endpoint measured the difference in efficacy of GS010 in treated eyes compared to sham-treated eyes based on BestCorrected Visual Acuity (BCVA), as measured with the ETDRS at 48 weeks post-injection. The patients LogMAR (Logarithm of the Minimal Angle of Resolution) scores, which are derived from the number of letters patients read on the ETDRS chart, were used for statistical purposes. Both trials were adequately powered to evaluate a clinically relevant difference of at least 15 ETDRS letters between drug-treated and sham-treated eyes, adjusted to baseline.

The secondary endpoints involved the application of the primary analysis to bestseeing eyes that received GS010 compared to those receiving sham, and to worseseeing eyes that received GS010 compared to those that received sham. Additionally, a categorical evaluation with a responder analysis was performed, including the proportion of patients who maintained vision (< ETDRS 15L loss), the proportion of patients who gained 15 ETDRS letters from baseline and the proportion of patients with Snellen acuity of >20/200. Complementary vision metrics included automated visual fields, optical coherence tomography, and color and contrast sensitivity, in addition to quality-of-life scales, biodissemination and the time course of immune response. Readouts for these endpoints were at 48, 72 and 96 weeks after injection.

The trials were conducted in parallel, in 37 subjects for REVERSE and 39 subjects for RESCUE, in 7 centers across the United States, the UK, France, Germany and Italy. Week 96 results were reported in 2019 for both trials, after which patients were invited to participate in a long-term follow-up study, RESTORE, for three additional years.

The primary objective is to assess the long-term safety of intravitreal LUMEVOQ administration up to 5 years post-treatment. The secondary objective is to assess the long-term treatment efficacy of the therapy and the quality of life (QoL) in subjects up to 5 years post-treatment. The first subject was enrolled on January 9, 2018. 61 subjects have enrolled.

ClinicalTrials.gov Identifiers:REVERSE: NCT02652780RESCUE: NCT02652767RESTORE: NCT03406104

Read more here:

GenSight Biologics Announces Publication of RESTORE Study Data Demonstrating Sustained Efficacy 3 Years After Unilateral Injection of LUMEVOQ -...

Novartis and the Bill and Melinda Gates Foundation are joining forces to discover and develop a gene therapy to cure sickle cell disease with a one-step, one-time treatment that is affordable and simple enough to treat patients anywhere in the world, especially in sub-Saharan Africa where resources may be scarce but disease prevalence is high.

The three-year collaboration, announced Wednesday, has initial funding of $7.28 million.

Current gene therapy approaches being developed for sickle cell disease are complex, enormously expensive, and bespoke, crafting treatments for individual patients one at a time. The collaboration aims to instead create an off-the-shelf treatment that bypasses many of the steps of current approaches, in which cells are removed and processed outside the body before being returned to patients.

advertisement

Sickle cells cause is understood. The people it affects are known. But its cure has been elusive, Jay Bradner, president of the Novartis Institutes for BioMedical Research, told STAT.

We understand perfectly the disease pathway and the patient, but we dont know what it would take to have a single-administration, in vivo gene therapy for sickle cell disease that you could deploy in a low-resource setting with the requisite safety and data to support its use, he said. Im a hematologist and can assure you that in my experience in the clinic, it was extremely frustrating to understand a disease so perfectly but have so little to offer.

advertisement

Sickle cell disease is a life-threatening inherited blood disorder that affects millions around the world, with about 80% of affected people in sub-Saharan Africa and more than 100,000 in the U.S. The mutation that causes the disease emerged in Africa, where it protects against malaria. While most patients with sickle cell share African ancestry, those with ancestry from South America, Central America, and India, as well as Italy and Turkey, can also have the hereditary disease.

The genetic mutation does its damage by changing the structure of hemoglobin, hampering the ability of red blood cells to carry oxygen and damaging blood vessels when the misshapen cells get stuck and block blood flow. Patients frequently suffer painful crises that can be fatal if not promptly treated with fluids, medication, and oxygen. Longer term, organs starved of oxygen eventually give out. In the U.S., that pain and suffering is amplified when systemic and individual instances of racism deny Black people the care they need.

Delivering gene therapy for other diseases has been costly and difficult even in the best financed, most sophisticated medical settings. Challenges include removing patients cells so they can be altered in a lab, manufacturing the new cells in high volume, reinfusing them, and managing sometimes severe responses to the corrected cells. Patients also are given chemotherapy to clear space in their bone marrow for the new cells.

Ideally, many of those steps could be skipped if there were an off-the-shelf gene therapy. That means, among other challenges, inventing a way to eliminate the step where each patients cells are manipulated outside the body and given back the in vivo part of the plan to correct the genetic mutation.

Thats not the only obstacle. For a sickle cell therapy to be successful, Bradner said, it must be delivered only to its targets, which are blood stem cells. The genetic material carrying corrected DNA must be safely transferred so it does not become randomly inserted into the genome and create the risk of cancer, a possibility that halted a Bluebird Bio clinical trial on Tuesday. The payload itself mustnt cause such problems as the cytokine storm of immune overreaction. And the intended response has to be both durable and corrective.

In a way, the gene delivery is the easy part because we know that expressing a normal hemoglobin, correcting the mutated hemoglobin, or reengineering the switches that once turned off normal fetal hemoglobin to turn it back on, all can work, Bradner said. The payload is less a concern to me than the safe, specific, and durable delivery of that payload.

For each of these four challenges delivery, gene transfer, tolerability, durability there could be a bespoke technical solution, Bradner said. The goal is to create an ensemble form of gene therapy.

Novartis has an existing sickle-cell project using CRISPR with the genome-editing company Intellia, now in early human trials, whose lessons may inform this new project. CRISPR may not be the method used; all choices are still on the table, Bradner said.

Vertex Pharmaceuticals has seen encouraging early signs with its candidate therapy developed with CRISPR Therapeutics. Other companies, including Beam Therapeutics, have also embarked on gene therapy development.

The Novartis-Gates collaboration is different in its ambition to create a cure that does not rely on an expensive, complicated framework. Novartis has worked with the Gates Foundation on making malaria treatment accessible in Africa. And in October 2019, the Gates Foundation and the National Institutes of Health said together they would invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV that would be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

Gene therapies might help end the threat of diseases like sickle cell, but only if we can make them far more affordable and practical for low-resource settings, Trevor Mundel, president of global health at the Gates Foundation, said in a statement about the Novartis collaboration. Its about treating the needs of people in lower-income countries as a driver of scientific and medical progress, not an afterthought.

Asked which is the harder problem to solve: one-time, in vivo gene therapy, or making it accessible around the world, David Williams, chief of hematology/oncology at Boston Childrens Hospital, said: Both are going to be difficult to solve. The first will likely occur before the therapy is practically accessible to the large number of patients suffering the disease around the world.

Williams is also working with the Gates Foundation, as well as the Koch Institute for Integrative Cancer Research at MIT, Dana-Farber Cancer Institute, and Massachusetts General Hospital, on another approach in which a single injection of a reagent changes the DNA of blood stem cells. But there are obstacles to overcome there, too, that may be solved by advances in both the technology to modify genes and the biological understanding of blood cells.

Bradner expects further funding to come to reach patients around the world, once the science progresses more.

There is no plug-and-play solution for this project in the way that mRNA vaccines were perfectly set up for SARS-CoV-2. We have no such technology to immediately redeploy here, he said. Were going to have to reimagine what it means to be a gene therapy for this project.

Read more:

Novartis, Gates Foundation pursue a simpler gene therapy for sickle cell - STAT