In a landmark phase 3 clinical trial, the international team, coordinated by Dr Patrick Yu-Wai-Man from the University of Cambridge and Dr Jos-Alain Sahel from the University of Pittsburgh and Institut de la Vision, Paris, successfully treated 37 patients suffering from Leber hereditary optic neuropathy (LHON). Subject to further trials, the treatment could help thousands of people across the world to regain and retain some of their sight.

The study, published today in the journal Science Translational Medicine, indicates that 78% of treated patients experienced significant visual improvement in both eyes. It suggests that the improvement in vision in untreated eyes could be due to the transfer of viral vector DNA from the injected eye.

LHON affects a specific type of retinal cells, known as retinal ganglion cells, causing optic nerve degeneration and rapidly worsening vision in both eyes. Within a few weeks of disease onset, the vision of most people affected deteriorates to levels at which they are considered legally blind. Visual recovery occurs in less than 20% of cases and few achieve vision better than 20/200 (largest letter on a standard eye chart). LHON affects approximately 1 in 30,000 people, mostly men, with symptoms usually emerging in their 20s and 30s. The majority of patients carry the m.11778G>A mutation in the MT-ND4 gene. Existing treatment for this blinding optic neuropathy remains limited.

As someone who treats these young patients, I get very frustrated about the lack of effective therapies, said senior investigator Dr Sahel, a professor of ophthalmology at the University of Pittsburgh. These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.

The researchers injected rAAV2/2-ND4 a viral vector containing modified cDNA into the vitreous cavity at the back of one eye of 37 patients who had suffered vision loss for between 6 to 12 months. Their other eye received a sham injection. The technology, called mitochondrial targeting, was developed by the Institut de la Vision in Paris, France, and licensed to GenSight Biologics.

International coordinating investigator and neuro-ophthalmologist Dr Yu-Wai-Man, from Cambridges Department of Clinical Neurosciences and Moorfields Eye Hospital, London, said: We expected vision to improve in the eyes treated with the gene therapy vector only. Rather unexpectedly, both eyes improved for 78% of patients in the trial following the same trajectory over 2 years of follow-up.

Treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) of 15 letters on an ETDRS chart, representing three lines of vision, while a mean improvement of 13 letters was observed in the sham-treated eyes. As some patients were still in the dynamic phase of the disease process upon enrolment, the visual gain from the nadir (worst BCVA for each eye) was even larger, reaching 28.5 letters for the treated eyes and 24.5 letters for sham-treated eyes.

Dr Yu-Wai-Man said: By replacing the defective MT-ND4 gene, this treatment rescues the retinal ganglion cells from the destructive effects of the m.11778G>A mutation, preserving function and improving the patients visual prognosis. The outcomes can be life-changing.

The researchers found that treated eyes were around three times more likely to achieve vision better than or equal to 20/200. Patient-reported outcome measures evaluated using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) also confirmed the positive impact of treatment on quality of life and psychosocial well-being.

The researchers then conducted a study in cynomolgus macaques to investigate how the treatment of one eye could bring about improvement in the other. Macaques have a visual system similar to that of humans, which allows the distribution and effects of the gene therapy vector to be studied in much greater detail. Unilateral injection of rAAV2/2-ND4 was administered and after three months, tissues from various parts of the eye and the brain were analyzed to detect and quantify the presence of viral vector DNA using a transgene-specific quantitative PCR assay.

Viral vector DNA was detected in the anterior segment, retina and optic nerve of the untreated eye. The unexpected visual improvement observed in the untreated eyes could therefore reflect the interocular diffusion of rAAV2/2-ND4. Further investigations are needed to confirm these findings and whether other mechanisms are contributing to this bilateral improvement.

Dr Yu-Wai-Man said: Saving sight with gene therapy is now a reality. The treatment has been shown to be safe and we are currently exploring the optimal therapeutic window.

Our approach isnt just limited to vision restoration, added Dr Sahel. Other mitochondrial diseases could be treated using the same technology.

Reference: Yu-Wai-Man P, Newman NJ, Carelli V, et al.Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy.Sci. Transl. Med. 2020;12(573). doi:10.1126/scitranslmed.aaz7423

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Gene Therapy Injection in One Eye Improves Vision in Both - Technology Networks

San Diego-based Locanabio secured $100 million in a Series B financing round that will be used to advance the companys portfolio of novel RNA-targeted gene therapies for neurodegenerative, neuromuscular and retinal diseases.

The funding will support pre-clinical and clinical development of its gene therapy treatments for diseases such as Huntington's disease, myotonic dystrophy type 1, genetic forms of amyotrophic lateral sclerosis and retinal disease, the company said.

Locanabio has a unique approach to gene therapy. The company has combined two validated gene therapy and RNA modifications to treat diseases. Locanabio uses a gene therapy vector to deliver an RNA-targeting protein tipped with an RNA-modifying enzyme. Through targeting RNA, the company said its approach avoids the risk of off-target effects in DNA and is suited to address many diseases linked to dysfunctional processing of RNA.

The $100 Million Series B builds on $55 million the company secured in a Series A last year. Chief Executive Officer Jim Burns, who joined Locanabio one year ago, said the financing round will allow the company to advance several of the companys most promising programs into IND-enabling studies in 2021. The financing will also allow the company to continue to advance its RNA-targeting platform, which has the potential to be a major new advance in medicine that can bring hope to patients with many devastating genetic diseases, Burns said.

While all of Locanabios assets are still in the research phase, its most advanced is a therapy for myotonic dystrophy type 1 (DM1), a genetic neuromuscular disorder caused by a mutation in the DMPK gene that results in trinucleotide (CUG) repeat expansion in the expressed RNA. Locanabios DM1 program targets and destroys the toxic CUG repeats, according to company information. Earlier this year, as BioSpace previously reported, Locanabio published a paper demonstrating the benefits of its technology as a potential one-time treatment of DM1.

The financing round was led by Vida Ventures LLC with participation from RA Capital Management, Invus, Acuta Capital Partners, an investment fund associated with SVB Leerink Prior Locanabio investors ARCH Venture Partners, Temasek, Lightstone Ventures, UCB Ventures and GV, also participated in the financing round.

"We are pleased that a team of highly sophisticated investors led by Vida Ventures has joined in this financing round, further validating our progress in research and the significant potential of our unique RNA-targeting platform, Burns said in a statement.

With the Series B, Rajul Jain, director of Vida Ventures, joined Locanabio's board of directors. Before Vida Ventures, Jain served on the executive team and headed development for Kite Pharma and was previously global development lead for Amgen.

The unique approach in RNA targeting using gene therapy to deliver RNA binding proteins developed by Locanabio represents the next frontier of genetic medicine with the ability to target the root cause of a range of genetic diseases, Jain said in a statement. They have built a strong management team to execute this bold vision and we are proud to support them.

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Locanabio Raises $100 Million to Advance RNA-Targeted Gene Therapies - BioSpace

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After a year that most of us want to forget, 2021 is shaping up to start with stability and an even keel. The election is safely behind us, the new Biden Administration promises a no drama approach, a closely divided and hyper-partisan Congress is unlikely to enact any sweeping legislation, reform or otherwise, and COVID vaccines are ready for distribution. Its a recipe for a calm news cycle.Which makes it a perfect time to buy into the stock market. Investors can read the tea leaves, or study the data whatever their preferred mode of stock analysis and use this period of calm to make rational choices on the stock moves. Using the TipRanks database, weve pulled up three stocks that present a bullish case. All three meet a profile that should interest value investors. They hold unanimous Strong Buy consensus ratings, along with a perfect 10 from the Smart Score. That score, a unique measure, evaluates a stock based on 8 factors with a proven high correlation to future overperformance. A 10 score indicates a strong likelihood that the stock will rise in the coming year. And finally, all three of these stocks present with double-digit upside potentials, indicating that they are still undervalued.UMH Properties (UMH)Well start in the real estate investment trust (REIT) sector, with UMH Properties. This company, which started out after WWII in the mobile home industry, later become the premier builder of manufactured housing. Today, UMH owns and manages a portfolio of 124 manufactured housing communities, spread across 8 states in the Northeast and Midwest, and totaling well over 23,000 units. As a REIT, UMH has benefitted from the nature of manufactured houses as affordable options in the housing market. UMH both sells the manufactured homes to residents, while leasing the plots on which the properties stand, and leases homes to residents. The companys same-property income, a key metric, showed 8.6% year-over-year increase in the third quarter.Also in the third quarter, UMH reported a 16% yoy increase in top line revenue, showing $43.1 million compared to $37.3 million in the year-ago quarter. Funds from Operations, another key metric in the REIT sector, came in at 11 cents per share, down from 14 cents in 3Q19. The decrease came as the company redeemed $2.9 million in Series B Preferred Stock.REITs are required to return income to shareholders, and UMH accomplishes this with a reliable dividend and a high yield of 4.7%. The payment, at 18 cents per common share, is paid quarterly and has been held stable for over a decade.Compass Point analyst Merrill Ross believes the company is in a sound position to create value for both households and shareholders."We believe that UMH has proven that it can bring attractive, affordable housing to either renters or homeowners more efficiently than has been possible with vertical rental housing. As UMH improves its cost of funds, it can compete more effectively with other MH community owners in the public and private realms, and because it has a successful formula to turn around undermanaged communities, we think that UMH can consolidate privately-owned properties over the next few years to build on its potential for value creation," Ross opined.To this end, Ross rates UMH a Buy, and her $20 price target implies a 25% one-year upside. (To watch Rosss track record, click here)Overall, the unanimous Strong Buy on UMH is based on 5 recent reviews. The stock is selling for $15.92, and the $18.40 average price target suggests it has room for 15% growth from that level. (See UMH stock analysis on TipRanks)Laird Superfood (LSF)Laird Superfood is a newcomer to the stock markets, having gone public just this past September. The company manufactures and markets a range of plant-based, nutrient-dense food additives and snacks, and is most known for its line of specialized non-dairy coffee creamers. Laird targets customers looking to add nutrition and an energy boost to their diet.Since its September IPO, the company has reported Q3 earnings. Revenue was strong, at $7.6 million, beating the forecast by over 26% and coming in 118% above the year-ago figure. The company also reported a 115% yoy growth in online sales. Ecommerce now makes up 49% of the companys net sales no surprise during the corona year.The review on the stock comes from Robert Burleson, a 5-star analyst from Canaccord. Burleson reiterates his bullish position, saying, We continue to view LSF as an attractive platform play on strong demand trends for plant-based, functional foods, noting LSFs competitively differentiated omni-channel approach and ingredients ethos. Over time, we expect LSF to be able to leverage its brand and vertically integrated operation into success in a broad range of plant-based categories, driving outsized top-line growth and healthy margin expansion.Burleson rates LSF shares a Buy alongside a $70 price target. This figure indicates his confidence in ~63% growth on the one-year horizon. (To watch Burlesons track record, click here)Laird has not attracted a lot of analyst attention, but those who have reviewed the stock agree with Burlesons assessment. LSF has a unanimous Strong Buy analyst consensus rating, based on 3 recent reviews. The stocks $62.33 average price target suggests room for ~39% upside in the coming year. (See LSF stock analysis on TipRanks)TravelCenters of America (TA)Last but not least is TravelCenters of America, a major name in the transportation sector. TravelCenters owns, operates, and franchises full-service highway rest stops across the US an important niche in a country that relies heavily on long-haul trucking, and in which private car ownership has long encouraged the road trip mystique. TAs network of rest stops offers travelers convenience stores and fast-food restaurants in addition to gasoline and diesel fuel and the expected amenities.The corona crisis has been hard time for TA, as lockdown regulations put a damper on travel. The companys revenues bottomed out in Q2, falling to $986 million, but rose 28% sequentially to hit $1.27 billion in Q3. EPS, at 61 cents, was also strong, and showed impressive 165% year-over-year growth. These gains came as the economy started reopening and with air travel still restricted, automobiles become the default for long distance, a circumstance that benefits TravelCenters. Covering TravelCenters for BTIG is analyst James Sullivan, who rates the stock a Buy, and his $40 price target suggests a 22% upside over the coming year. (To watch Sullivans track record, click here)Backing his stance, Sullivan noted, "TA is in the process of moving on from a series of unsuccessful initiatives under the prior management team. The current new management team has strengthened the balance sheet and intends to improve operations through both expense cuts and revenue-generating measures which should boost margins [...] While we expect the 2020 spend to be focused on non-revenue generating maintenance and repair items, we expect in 2021 and beyond that higher spending should generate good ROI All in all, TravelCenters shares get a unanimous thumbs up, with 3 Buys backing the stocks Strong Buy consensus rating. Shares sell for $32.87, and the average price target of $38.33 suggests an upside potential of ~17%. (See TA stock analysis on TipRanks)To find good ideas for stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Worldwide Gene Therapy Industry to 2025 - Cancer is Expected to Hold Significant Market Share in the Indication Segment - ResearchAndMarkets.com -...

DALLAS--(BUSINESS WIRE)--Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system in both rare and large patient populations, today announced that it is set to join the Russell 2000 Index, effective Monday, December 21, 2020, as part of the indexs quarterly initial public offering (IPO) additions.

The Russell 2000 Index measures the performance of the small-cap segment of the U.S. equity market. The index is a subset of the Russell 3000 Index and represents approximately 10 percent of the total market capitalization of that index. Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $9 trillion in assets are benchmarked against Russells U.S. indexes. Russell indexes are part of FTSE Russell, a leading global index provider.

For more information on the Russell 2000 Index and the Russell indexes IPO additions, please visit the Russell U.S. Index IPO Additions section on the FTSE Russell website.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available at http://www.tayshagtx.com.

About FTSE Russell

FTSE Russell is a leading global index provider creating and managing a wide range of indexes, data and analytic solutions to meet client needs across asset classes, style and strategies. Covering 98% of the investable market, FTSE Russell indexes offer a true picture of global markets, combined with the specialist knowledge gained from developing local benchmarks around the world.

FTSE Russell index expertise and products are used extensively by institutional and retail investors globally. Approximately $16 trillion is currently benchmarked to FTSE Russell indexes. For over 30 years, leading asset owners, asset managers, ETF providers and investment banks have chosen FTSE Russell indexes to benchmark their investment performance and create investment funds, ETFs, structured products and index-based derivatives. FTSE Russell indexes also provide clients with tools for asset allocation, investment strategy analysis and risk management.

A core set of universal principles guides FTSE Russell index design and management: a transparent rules-based methodology is informed by independent committees of leading market participants. FTSE Russell is focused on index innovation and customer partnership applying the highest industry standards and embracing the IOSCO Principles. FTSE Russell is wholly owned by London Stock Exchange Group.

For more information, visit http://www.ftserussell.com.

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Taysha Gene Therapies Set to Join Russell 2000 Index on December 21, 2020 - Business Wire

Rare Disease Gene Therapy Market: Snapshot

The global rare disease gene therapy is expected to witness a significant growth in the forecast period, 2020-2030 on account of the increasing cases of genetic diseases worldwide. Gene therapy is relevant to rare disease patients and has improved the wellbeing and personal satisfaction of more seasoned kids and youthful grown-ups with X-SCID. These kids are expected to experience complex clinical issues in the wake of getting live-sparing bone marrow transfers to treat the condition.

The report offers insights into the market emphasizing on factors boosting, repelling, challenging, and creating opportunities for the market in the forecast period. It also discusses the impact of the COVID-19 pandemic on the overall market. It also discusses the table of segmentation in details and lists the names of the prominent players functioning in the market.

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The global rare disease gene therapy market is categorized on the basis of type, indication, administration, distribution channel, and region. In terms of type, the market is bifurcated into non-viral vector gene therapy, and viral vector gene therapy. In terms of indication, the market is grouped into inflammatory diseases, neurological diseases, infectious diseases, hematology diseases, oncology diseases, genetic diseases, and others. With respect to segmentation by distribution channel, the market is categorized into online pharmacies, drugstores, retail pharmacies, and hospital pharmacies.

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Rare Disease Gene Therapy Market: Competitive Landscape

Expanding collective innovative work exercises among driving biopharmaceutical imaginative players is required to fuel the development of uncommon sickness quality treatment market. What's more, clinical-stage improvement organizations are allotting critical assets towards the advancement of the uncommon illness quality treatment market.

For example, in August 2020, the U.S. based Ovid Therapeutics teamed up with Italian firm Angelini Pharma to create, make and popularize drug gaboxadol for treatment of Angelman disorder (uncommon hereditary sickness) in European market.

Some of the players of the global rare disease gene therapy market include Amgen Inc., AbbVie Inc., F.Hoffmann-La Roche Ltd., Merck & Co., Johnson & Johnson, Baxter, Novo Nordisk A/S, Alexion, Pfizer Inc., Bristol-Myers Squibb Company, Novartis AG, Sanofi S.A., Teva Pharmaceutical Industries Ltd., Bayer AG, Allergen plc., Vertex Pharmaceuticals, and others.

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Rare Disease Gene Therapy Market: Interesting Insights

There has been an intense competition among biopharmaceutical players to create Covid treatment that is postponing on account of innovative work exercises in uncommon infection quality treatment market. Stop of assembling exercises and flexibly tie disturbance because of exchanging across outskirts will have sway on uncommon illness quality treatment market development rate. The decrease in treatment selection rate attributable to diminished patient visits to medical services offices will lessen development pace of uncommon sickness quality treatment market. The increasing number of uncommon infections is relied upon to drive the development of uncommon illness quality treatment market.

Furthermore, the expanding synergistic innovative work exercises among driving biopharmaceutical inventive players is relied upon to fuel the development of uncommon infection quality treatment market. Also, clinical-stage advancement organizations are allotting critical assets towards the improvement of the uncommon infection quality treatment market.

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Rare Disease Gene Therapy Market: Increasing cases of genetic diseases to drive the market - BioSpace

One of the ways scientists hope to offer better treatments for vision loss is through gene therapy, where carefully selected genetic material is injected into the eyes to address mutations. Researchers have been left surprised by the effectiveness of an experimental form of this treatment, which involved an injection into one eyeball yet improved vision across both.

Gene therapies have the potential to treat all kinds of health conditions, ranging from cancer, to diabetes in dogs, to obesity and damaged spinal cords. One area where we're seeing some really exciting progress is in hereditary vision loss, with studies demonstrating the potential of gene therapy to treat color blindness, progressive retinal diseases and glaucoma, with some recently receiving approval from the FDA.

This latest study was conducted by scientists at the University of Cambridge, the University of Pittsburgh and Paris Institut de la Vision, and focuses on a form of inherited vision loss called Leber hereditary optic neuropathy (LHON). This affects around one in 30,000 people and usually occurs in young folks aged in their 20s and 30s, destroying their retinal ganglion cells and in turn the optic nerve. Once the condition takes hold, vision can deteriorate to the point where the subject is considered legally blind in just a matter of weeks, with recovery occurring in less than 20 percent of cases.

The majority of patients suffer from the same mutation affecting the MT-ND4 gene, so the researchers were hopeful of targeting this mutation as a way of improving treatment outcomes for sufferers of LHON. They trialed their gene therapy as part of a study involving 37 patients who had suffered vision loss in the preceding six to 12 months. This meant injecting a viral vector packed with a modified complementary DNA called rAAV2/2-ND4 into the vitreous cavity at the back of just one eye, with a sham treatment injected into the other eye.

We expected vision to improve in the eyes treated with the gene therapy vector only, says study author Dr Yu-Wai-Man. Rather unexpectedly, both eyes improved for 78 percent of patients in the trial following the same trajectory over two years of follow-up.

To investigate the reasons behind this unexpected outcome, the team studied the gene therapys effects in macaques, which have a similar vision system to humans. This enabled them to analyze the tissues from different parts of the eye to see how the viral vector DNA had spread. This provided evidence of interocular diffusion, with the viral vector DNA turning up in the retina, optic nerve and anterior segment of the untreated eye.

As someone who treats these young patients, I get very frustrated about the lack of effective therapies, says senior investigator Dr Sahel, from the University of Pittsburgh. These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.

The research was published in the journal Science Translational Medicine.

Source: University of Cambridge

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Single gene therapy injection surprisingly boosts vision in both eyes - New Atlas

Bearing the usual perils of cross-trial comparisons in mind, the much larger Hope-B pivotal trial of Uniqures etranacogene dezaparvovec (AMT-061) found mean FIX activity of 37% of normal at 26 weeks, taking severe haemophilia B patients into the range seen in mild disease (Ash 2020 hints of durability emerge for Uniqure's gene therapy, December 8, 2020).

Although this has been heralded as a huge advance, around 30% of patients in Hope-B did not reach 30% FIX activity, and some participants still experienced bleeds.

Freeline hopes to go one step further and eliminate serious bleeds, returning haemophilia B patients to a normal life. The company noted that in B-Amaze there were no bleeds that needed FIX supplementation.

The increased FIX activity seen with verbrinacogene setparvov is down to Freelines novel synthetic capsid, called AAVS3, the companys founder, Professor Amit Nathwani of University College London, explained during yesterdays call. He said the capsid leads to three to sixfold higher levels of gene transfer compared with other, wild-type capsids, which in turn should spur high levels of protein expression using relatively low doses of vector.

However, Uniqures capsid might have an edge in one respect: Hope-B did not exclude patients with pre-existing neutralising antibodies to AAV.

Freelines trial did include some patients with neutralising antibodies, Ms Krop told Evaluate Vantage, although there was a cut-off over which patients with these antibodies were excluded. This was intentionally low, Ms Heggie added, without giving details.

Although the data from B-Amaze look promising, the patient numbers involved are small, and Freeline now needs to show that its claims hold up in a bigger population. The pivotal trial will enrol 20 patients initially, and the phase IIb portion will be used to confirm the dose before moving into the phase III portion.

Freeline hopes it will be able to file for accelerated approval based on 26-week FIX data along with 52-week annualised bleeding rate data in a subset of these patients. The study will then enrol up to 30 more patients to evaluate 52-week ABR, which is designed to support full approval.

It is too early to call a winner in haemophilia B gene therapy, according to Evercore ISIs Josh Schimmer, who added: Uniqure has a bird in the hand with its dataset while Freeline has a couple of promising ones in the bush.

Ms Heggie is not concerned about not being first to market. We know we're probably two years behind Uniqure, but we know patients will wait for the best treatment.

She also told Evaluate Vantage that, while Freeline is not yet discussing pricing, we expect to have really strong value proposition if, as we expect, itll be a functional cure.

Freeline still has a lot of work to do, but Uniqure might soon have some real competition.

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Freeline takes the haemophilia B gene therapy fight to Uniqure - Vantage

People with hemophilia B lack a protein that helps their blood clot, so they rely on lifelong infusions of that protein to manage their disease. UniQure and CSL Behrings hemophilia B gene therapy could transform chronic care into a one-time treatmentand its latest data suggest it could work for patients considered unsuitable for gene therapy.

The treatment, etranacogene dezaparvovec, curbed bleeding episodes and nearly eliminated the need for infusions of clotting Factor IX (FIX) in a phase 3 study testing it in severe or moderately severe hemophilia B. The study, HOPE-B, found that 26 weeks after treatment, the gene therapy had reduced bleeds that needed treatment by 91%, with 87% of 54 patients reporting such bleeds. Eighty-three percent of the patients reported no bleeds at all, including suspected bleeds that did not require treatment.

RELATED: BioMarin's hemophilia gene therapy 'Roc solid' after 4 years

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The treatment also boosted FIX activity to an average of 37.2%, up from less than 2% at the start of the trial, meeting its primary endpoint.

The study, to be presented virtually Tuesday at the annual meeting of the American Society of Hematology, found that nearly all the patients52 out of 54, or 98%no longer needed infusions of FIX to prevent bleeding episodes. Of the remaining two patients, one suffered an infusion reaction during treatment and did not get the full gene therapy dose, while the other had very high levels of antibodies that neutralize the adeno-associated virus (AAV) used to deliver the treatment.

Many people have a natural immunity to AAVs because theyre exposed to them in the environment. Though useful for fighting off infection, this immunity can render gene therapies ineffective. That appears not to be the case with uniQure and CSLs treatment. The patient for whom the gene therapy did not work was an outlier, with antibody levels nearly five times as high as the level expected in more than 95% of the general population. In patients with more typical antibody levels, investigators saw no correlation between the presence of those antibodies and FIX activity, the company said in a statement.

Importantly, these data also show that those patients in the trial who may not have been eligible for other gene therapies because they had pre-existing neutralizing antibodies (NAbs) have achieved results with etranacogene dezaparvovec that are comparable to the results of patients who did not have pre-existing NAbs, Steven Pipe, M.D., a professor of pediatrics and pathology at the University of Michigan and the studys lead investigator, said in a statement.

RELATED: CSL to pay $450M to buy uniQure's hemophilia B gene therapy

This is an important distinction as this is the only known clinical trial that has maximized patient eligibility in this way. The initial data also show that etranacogene dezaparvovec has been generally well tolerated to date, he said.

Most of the side effects were mild (82%). The most common treatment-related side effect was elevated liver enzymes, which affected 17% of patients but was treated effectively with steroids. Infusion reactions and flu-like symptoms each affected 13% of patients.

The data come five months after CSLpicked up the global rights to etranacogene dezaparvovec for $450 million upfront. These latest data set up the companies in a battle to bring a new hemophilia B gene therapy to market, pitting them against the likes of Pfizer and Spark/Roche.

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ASH: UniQure/CSL hem B gene therapy curbs bleeding in phase 3even in patients with anti-AAV antibodies - FierceBiotech

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --The gene therapy etranacogene dezaparvovec substantially increased production of the blood clotting protein factor IX among 52 patients in the largest and most inclusive hemophilia B gene therapy trialto date. The trial is also the first to include patients with certain immune system markers and found that they did not appear to confer any increased risks, a finding that could significantly broaden the number of patients who may be eligible for gene therapy.

A majority of trial participants (96%) successfully discontinued factor IX replacement therapy after receiving the gene therapy and have been producing their own factor IX for six months. The findings suggest gene therapy could, with a single treatment, give patients the ability to maintain factor IX levels and reduce or eliminate the need for additional factor IX replacement therapy, according to researchers.

"Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life," said senior study authorSteven W. Pipe, MD,of the University of Michigan, Ann Arbor. "Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life."

Hemophilia B, which accounts for about one-fifth of hemophilia cases, is caused by an inherited mutation of the gene for factor IX. Lacking the ability to produce the blood clotting factor IX, patients with hemophilia B can suffer uncontrolled bleeding, including internal and joint bleeding that leads to joint deterioration and chronic pain.

Factor IX replacement therapy can reduce bleeding associated with hemophilia B, but it requires weekly or biweekly infusions to maintain factor IX levels, a burdensome regimen that costs several hundred thousand dollars per year. In gene therapy, viral particles are used to shuttle engineered genes to cells in the liver. These genes replace the patient's faulty factor IX gene, allowing the patient's own body to produce factor IX on an ongoing basis. While several gene therapies for hemophilia have shown promise in early phase trials, the study is the first phase III trial to test the approach in a large and diverse array of patients, said Dr. Pipe.

Fifty-four patients enrolled in the study; all were dependent on factor IX replacement therapy, and 70% had bleeding episodes in the six months prior to the study despite this prophylactic treatment. After receiving the etranacogene dezaparvovec gene therapy via a single infusion lasting roughly one hour, factor IX activity increased rapidly from a baseline of up to 2% (moderate to severe hemophilia) to a mean of 37% (very mild hemophilia) at 26 weeks, meeting the trial's primary endpoint. At that level, a patient's bleeding risk is essentially the same as someone without hemophilia, Dr. Pipe noted.

Seventy-two percent of patients reported no bleeding events in the 26 weeks after receiving the gene therapy. "This tells us that the bleeding phenotype can be corrected through this treatment, which is a remarkable achievement," said Dr. Pipe. Fifteen patients experienced some bleeding, which the researchers indicate is not unexpected given that many of the patients had severely affected joints entering the trial.

"What we've seen from patients in the study is that they really don't have to think about their hemophilia anymore," said Dr. Pipe. "The transformative nature that we hear from the patient stories is, to me, the most important outcome from this study."

The trial is also the first to attempt gene therapy in patients with neutralizing antibodies, a component of the immune system that helps the body fight pathogens. About 40% of trial participants had antibodies to adeno-associated virus serotype 5, or AAV5, the viral vector used in etranacogene dezaparvovec. "In any other trial protocol, these patients would not have been eligible to participate," Dr. Pipe noted.

Previous trials have excluded such patients from gene therapies that use viral vectors under the assumption that antibodies could either block the uptake of the viral vectors in the liver or trigger a dangerous immune response to the therapy. The trial found no evidence of either problem, suggesting neutralizing antibodies do not preclude successful gene therapy.

Two patients did not respond to the gene therapy. One did not receive a full dose because the infusion was stopped after the patient showed signs of a reaction to the infusion. The other had a level of neutralizing antibodies about five times higher than any other patient. Since other patients with neutralizing antibodies responded well to the therapy regardless of their level of antibodies, this finding suggests antibodies may pose a problem only at extremely high levels.

No treatment-related serious adverse events were reported. Adverse events were relatively common, occurring in 68% of patients, but most were mild and related to the infusion itself. Nine patients showed evidence of an immune response to the therapy, which was resolved in all cases with a course of corticosteroids.

The researchers will continue to follow patients for five years. Patients will be assessed for sustained factor IX production and effective bleed control over 52 weeks, as well as patient-reported outcome measures to assess impact on quality of life.

Steven W. Pipe, MD, University of Michigan, Ann Arbor, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Gene Therapy for Hemophilia B Found Safe and Effective in First Phase III Trial - PRNewswire

DUBLIN--(BUSINESS WIRE)--The "Global Gene Therapy Market - Analysis By Vector Type, By Application, By Region, By Country (2020 Edition): Market Insights, Covid-19 Impact, Competition and Forecast (2020-2025)" report has been added to ResearchAndMarkets.com's offering.

Global Gene Therapy Market was valued at USD 1221.84 Million in the year 2019.

Escalating number of cases related to various chronic diseases including Cancer, Cardiovascular and Neurological Disorders, Alzheimer's and Sickle Cell Diseases, with companies investing heavily in incorporating advanced technology supported by growing collaboration between bio-pharma companies and research institutes to advance in the field of Gene therapy, has been anticipated to infuse growth in the market for Gene Therapy during the forecast period of 2020-2025.

Under the Vector Type segment, AAV vectors, followed by Retrovirus & Gammaretrovirus and Lentivirus, are anticipated to witness the largest market share owing to growing investment in adeno-associated viral (AAV) vectors to advance research programs against strategically selected cell targets. Increasing prevalence of various diseases across the globe will further accelerate the gene therapy market growth during the coming years.

Among the regions, North America, followed by Europe and Asia Pacific, will experience remarkable market share owing to the presence of various leading global companies including Orchard Therapeutics, Voyager Therapeutics, and Spark Therapeutics. With companies investing in adoption of advanced technology supported by enhanced focus on expanding product pipeline by manufacturers to advance in the field of Gene Therapy will further facilitate the market growth during the forecast period.

Scope of the Report

Key Topics Covered:

1. Research Methodology and Executive Summary

1.1 Research Methodology

1.2 Executive Summary

2. Strategic Recommendations

3. Gene Therapy Market: Product Outlook

4. Global Gene Therapy Market: Sizing and Forecast

4.1 Market Size, By Value, Year 2015-2025

5. Global Gene Therapy Market Segmentation - By Vector Type, and By Application

5.1 Competitive Scenario of Global Gene Therapy Market: By Vector Type

5.1.1 Lentivirus - Market Size and Forecast (2015-2025)

5.1.2 AAV - Market Size and Forecast (2015-2025)

5.1.3 Retrovirus & Gammaretrovirus - Market Size and Forecast (2015-2025)

5.1.4 Others - Market Size and Forecast (2015-2025)

5.2 Competitive Scenario of Global Gene Therapy Market: By Application

5.2.1 Neurological Disorders - Market Size and Forecast (2015-2025)

5.2.2 Cancer - Market Size and Forecast (2015-2025)

5.2.3 Cardiovascular Diseases - Market Size and Forecast (2015-2025)

5.2.4 Others - Market Size and Forecast (2015-2025)

6. Global Gene Therapy Market: Regional Analysis

6.1 Competitive Scenario of Global Gene Therapy Market: By Region

7. North America Gene Therapy Market: An Analysis (2015-2025)

7.1 North America Gene Therapy Market: Size and Forecast (2015-2025), By Value

7.2 North America Gene Therapy Market - Prominent Companies

7.3 Market Segmentation By Vector Type (Lentivirus, AAV, Retrovirus & Gammaretrovirus and Others)

7.4 Market Segmentation By Application (Neurological Disorders, Cancer, Cardiovascular Diseases and Others)

7.5 North America Gene Therapy Market: Country Analysis

7.6 Market Opportunity Chart of North America Gene Therapy Market - By Country, By Value, 2025

7.7 Competitive Scenario of North America Gene Therapy Market : By Country

7.8 United States Gene Therapy Market: Size and Forecast (2015-2025), By Value

7.9 United States Gene Therapy Market Segmentation - By Vector Type, and By Application (2015-2025)

7.10 Canada Gene Therapy Market: Size and Forecast (2015-2025), By Value

7.11 Canada Gene Therapy Market Segmentation - By Vector Type, and By Application (2015-2025)

8. Europe Gene Therapy Market: An Analysis (2015-2025)

9. Asia Pacific Gene Therapy Market: An Analysis (2015-2025)

10. Global Gene Therapy Market Dynamics

10.1 Drivers

10.2 Restraints

10.3 Trends

11. Market Attractiveness

11.1 Market Attractiveness Chart of Global Gene Therapy Market - By Vector Type, 2025

11.2 Market Attractiveness Chart of Global Gene Therapy Market - By Application, 2025

11.3 Market Attractiveness Chart of Global Gene Therapy Market - By Region, 2025

12. Competitive Landscape

12.1 Major Technological Innovations, Mergers & Acquisitions and Role of Manufacturers During COVID-19

12.2 Product Pipeline of Leading Gene Therapy Companies

12.3 Market Share Analysis

13. Company Analysis (Business Description, Financial Analysis, Business Strategy)

13.1 Voyager Therapeutics

13.2 Novartis AG

13.3 Spark Therapeutics Inc.

13.4 MoldMed S.P.A.

13.5 Orchard Therapeutics PLC

13.6 Alnylam Pharmaceuticals Inc.

13.7 AnGes Inc.

13.8 Akcea Therapeutics

13.9 BlueBird Bio Inc.

13.10 Sarepta Therapeutics

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

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Gene Therapy Market Analysis by Vector Type, Application, Region - Global Market Insights, Covid-19 Impact, Competition and Forecast to 2025 -...

VALLEY COTTAGE, N.Y. Future Market Insights (FMI) presents its new, comprehensive study on the global Retinal Gene Therapy market spanning forecast. Researches at FMI have no left no stone unturned in bestowing readers a comprehensive view of the market, by studying the drivers, trends, challenges, and restraints. Backed by historical data and projected data, the report breaks down the vast study into numerous geographies and end-use segments, among others to condense the research. The report also considers production and consumption analysis, value chain analysis, key findings, important suggestions and recommendations, and other aspects

Analysts at FMI have employed in-depthanalysis to offer a lucid understanding of the market and the factors shapingits growth trajectory. Ranging from macro socio-economic factors to microgeography-specific trends, the research has taken into consideration everyfacet that is likely to play a vital role in the growth of the market in theyears to come. Presenting a plethora of valuable information, the report willserve as an effective tool, guiding the market players in making fruitfuldecisions in the forthcoming years.

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Impact of COVID-19on Retinal Gene Therapy Market

The unforeseen outbreak of COVID-19,which swiftly metamorphosed into the pandemic of unexpected proportions, hasshifted the worlds focus towards the healthcare sector. National governmentsare closely working with healthcare institutions and pharmaceutical companiesto provide effective treatment to patients suffering with the infection. As aresult, there has been a reorientation of medical priorities across healthcareinstitutions with treatment for COVID-19 patients being the utmost priority.This is sure to impact the growth of the Retinal Gene Therapy market throughthe pandemic period.

FMIs report includes a dedicated sectionexpounding both the short-term and long-term impact of the pandemic on the RetinalGene Therapy market. The study is shaped to bolster stakeholders in making theright decisions to mitigate challenges and leverage opportunities through thepandemic.

Why Choose FutureMarket Insights?

Retinal GeneTherapy Market: Segmentation

To simply the gargantuan study, thereport is segregated on the basis of different segments.

By Type:

By End User:

By Region:

The aforementioned segments are studiedwith respect to each individual region, considering the region-specific trends,drivers and restraints.

Retinal GeneTherapy Market: Competition Analysis

The study bestows valuable insightsinto the competitive landscape of the global Retinal Gene Therapy market, bystudying numerous players, their growth strategies, and key developments. Thereport dwells deep and studies different facets such as product launches,production methodologies, and steps adopted by players to make processescost-effective, among others, are expected to influence their individualstandpoint. Understanding the prevailing trends and strategies on thesupply-side empowers players to foster their plan of action accordingly toprogress on a remunerative path.

Request forReports TOC @ https://www.futuremarketinsights.com/toc/rep-gb-10246

Key QuestionsAnswered in FMIs Retinal Gene Therapy Market Report

About FMI:Future Market Insights (FMI) is a leading provider of market intelligence and consulting services, serving clients in over 150 countries. FMI is headquartered in Dubai, the global financial capital, and has delivery centers in the U.S. and India. FMIs latest market research reports and industry analysis help businesses navigate challenges and make critical decisions with confidence and clarity amidst breakneck competition. Our customized and syndicated market research reports deliver actionable insights that drive sustainable growth. A team of expert-led analysts at FMI continuously tracks emerging trends and events in a broad range of industries to ensure that our clients prepare for the evolving needs of their consumers.

Contact Us: Mr. Abhishek BudholiyaUnit No: AU-01-H Gold Tower (AU), Plot No: JLT-PH1-I3A,Jumeirah Lakes Towers, Dubai,United Arab EmiratesMARKET ACCESS DMCC InitiativeFor Sales Enquiries: sales@futuremarketinsights.comFor Media Enquiries: press@futuremarketinsights.comWebsite: https://www.futuremarketinsights.com

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Retinal Gene Therapy Market to Witness Sales Slump in Near Term Due to COVID-19; Long-term Outlook R - PharmiWeb.com

This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Childrens Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta-thalassemia. (Update: edit to fix attribution).

These diseases have long been linked when it comes to gene therapy ideas, because both of them have defects in the hemoglobin protein as their cause. And its long been thought that both could be treated by getting adults to re-express the fetal hemoglobin protein its on a different gene entirely, and thus does not have any of the genetic problems that affect the adult hemoglobin gene. The normal course of events is for babies to stop expressing the fetal form and switch over to regular hemoglobin, and its been worked out that a particular transcription factor called BCL11a is a key player in that transcriptional repression of the fetal hemoglobin gene. That plays right into the usual way that we tend to think about therapeutic possibilities: whether its enzymes, receptors, or expression of whole proteins, we have a lot more tools to mess things up and interrupt processes than we have to make them run faster or better. So the possibility of interrupting BCL11as function has been a tempting one for many years.

Its hard to do by traditional means, though. (Full disclosure: I have, at different times in my career, been involved with such efforts, but none have ever come near the clinic.) Transcription factors are notoriously hard to get a handle on with small molecule therapeutics, and many unsuccessful runs have been taken at BCL11a ligands to try to interrupt its functions in one way or another. My general impression is that the protein doesnt much care about recognizing small-molecule ligands (and its far from the only one in that category, for sure). Youd think that if you ran a few hundred thousand (or a few million) various molecules past any given protein that youd find a few of them that bind to it, but that assumption is too optimistic for most transcription factors. Youre also going to have a hard row to hoe (to use an old Arkansas expression) if you try to break up their interactions with their DNA binding sites: a significant amount of capital has gone down the chute trying to get that to work, with (as far as I can tell) not much to show for it.

Theres another complication: BCL11a has a lot of other functions. Every protein has a lot of other functions, but for transcription factors, the issue can be especially fraught. If you had a small molecule that really did interfere with its activity, what would happen if you just took a stiff dose of it? Probably a number of things, including some interesting (and not necessarily welcome) surprises. There have been a number of ideas about how to get around this problem, but a problem it is.

So its on to biological mechanisms. The BCH team reports on using RNA interference to do the job they get cells to express a short hairpin RNA that shuts down production of BCL11a protein, with some microRNA work to target this to the right cell lines. And the Vertex/CRISPR team, naturally, uses CRISPR itself to go in and inactivate the BCL11a gene directly. Both approaches take (and have to take) a similar pathway, which is difficult and expensive, but still the best shot at such therapies that we have. You want the fetal hemoglobin expressed in red blood cells, naturally, and red blood cells come from CD34+ stem cells in the bone marrow. Even if you havent thought about this, you might see where its going: you take a bone marrow sample, isolate these cells, and then do your genetic manipulation to them ex vivo. Once youve got a population of appropriately re-engineered cells ready to go, you go kill off the bone marrow in the patient and put the reworked cells back in, so theyre the only source there for red blood cells at all. A bone marrow transplant, in other words a pretty grueling process, but definitely not as much as having some sort of blood-cell-driven cancer (where the therapy uses compatible donor cells from someone else without such a problem), or as much as having full-on sickle cell disease or tranfusion-dependent thalassemia.

You can also see how this is a perfect setup for gene therapy: theres a defined population of cells that you need to treat, which are available in a specific tissue via a well-worked-out procedure. The problem youre trying to correct is extremely well understood in fact, it was the first disease ever characterized (by Linus Pauling in 1949) as purely due to a genetic defect . And the patients own tissue is vulnerable to chemotherapy agents that will wipe out the existing cell population, in another well-worked-out protocol, giving the newly reworked cells an open landscape to expand in. You have the chance for a clean swap on a defined target, which is quite rare. In too many other cases the problem turns out to involve a fuzzy mass of genetic factors and environmental ones, none of which by themselves account for the disease symptoms, or the tissue doesnt allow you to isolate the defective cells easily or doesnt allow you to clear them out for any new ones you might generate, and so on.

Both the Vertex/CRISPR and BCH techniques seem to work and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. Thats not a word we get to use very often. They are producing enough fetal hemoglobin, more than enough to make their symptoms completely disappear no attacks, no transfusions, just normal life. And so far there have been no side effects due to the altered stem cells. An earlier strategy from Bluebird (involving addition of a gene for a modified adult hemoglobin) also seems to be holding up.

These are revolutionary proofs of concept, but at the same time, they are not going to change the course of these diseases in the world not right now, anyway. Bone marrow transfusion is of course a complex process that costs a great deal and can only be done in places with advanced medical facilities. But what weve established is that anything that can cause fetal hemoglobin to be expressed should indeed cure these diseases that idea has been de-risked. As has the general idea of doing such genetic alteration in defined adult tissues (either RNA interference or CRISPR). From here, we try to make these things easier, cheaper and more general, to come up with new ways of realizing these same goals now that we know that they do what we hoped that they would. This work is already underway new ways to target the affected cell populations rather than flat-out chemotherapy assault, new ways to deliver the genetically altered cells (or to produce them on site in the patients), ways to make the switchover between the two more gradual, and so on. There are lot of possible ways, and we now know where were going.

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Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from Group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. These data are being presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease. Consistently achieving the complete resolution of severe vaso-occlusive events (VOEs) and VOEs between Month 6 and Month 24 follow-up is unprecedented other than with allogeneic stem cell transplantation. Importantly, our data show the potential for LentiGlobin for SCD to produce fundamentally disease-modifying effects with sustained pancellular distribution of gene therapy-derived anti-sickling HbAT87Q and improvement of key markers of hemolysis that approach normal levels, said David Davidson, M.D., chief medical officer, bluebird bio. In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD. These results provide insight into the potential real-life impact LentiGlobin for SCD may offer patients.

SCD is a serious, progressive and debilitating genetic disease. In the U.S., the median age of death for someone with sickle cell disease is 43 46 years. SCD is caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs.

In the HGB-206 study of LentiGlobin for SCD, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As a hematologist, I regularly see the debilitating effects of pain events caused by sickle cell disease. Pain has an overwhelmingly negative impact on many facets of my patients lives and can lead to prolonged hospitalizations, said presenting study author Alexis A. Thompson, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine and head of hematology at Ann and Robert H. Lurie Childrens Hospital of Chicago. The results observed with LentiGlobin gene therapy for SCD include the complete elimination of severe vaso-occlusive pain episodes, which is certainly clinically meaningful, but also for the first time, we have documented patients reporting that they are experiencing improved quality of life. This degree of early clinical benefit is extraordinarily rewarding to observe as a provider."

As of the data cut-off date of August 20, 2020, a total of 44 patients have been treated with LentiGlobin for SCD in the HGB-205 (n=3) and HGB-206 (n=41) clinical studies. The HGB-206 total includes: Groups A (n=7), B (n=2) and C (n=32).

HGB-206: Group C Updated Efficacy Results

The 32 patients treated with LentiGlobin for SCD gene therapy in Group C of HGB-206 had up to 30.9 months of follow-up (median of 13.0; min-max: 1.1 30.9 months).

In patients with six or more months of follow-up whose hemoglobin fractions were available (n=22), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin at Month 6. At last visit reported, total hemoglobin ranged from 9.6 15.1 g/dL and HbAT87Q levels ranged from 2.7 8.9 g/dL. At Month 6, the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin; median HbS was 50% and remained less than 60% at all follow-up timepoints. All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.

Nineteen patients treated in Group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD. There have been no reports of severe VOEs in these Group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after Month 6.

Hemolysis Markers

In SCD, red blood cells become sickled and fragile, rupturing more easily than healthy red blood cells. The breakdown of red blood cells, called hemolysis, occurs normally in the body. However, in sickle cell disease, hemolysis happens too quickly due to the fragility of the red blood cells, which results in hemolytic anemia.

Patients treated with LentiGlobin for SCD in Group C demonstrated near-normal levels in key markers of hemolysis, which are indicators of the health of red blood cells. Lab results assessing these indicators were available for the majority of the 25 patients with 6 months of follow-up.

The medians for reticulocyte counts (n=23), lactate dehydrogenase (LDH) levels (n=21) and total bilirubin (n=24) continued to improve compared to screening values and stabilized by Month 6. In patients with Month 24 data (n=7), these values approached the upper limit of normal by Month 24. These results continue to suggest that treatment with LentiGlobin for SCD may improve biological markers to near-normal levels for SCD.

Pancellularity

As previously reported, assays were developed by bluebird bio to enable the detection of HbAT87Q and HbS protein in individual red blood cells, as well as to assess if HbAT87Q was pancellular, or present throughout all of a patients red blood cells. In 25 patients with at least six months of follow-up, on average, more than 80% of red blood cells contained HbAT87Q, suggesting near-complete pancellularity of HbAT87Q distribution and with pancellularity further increasing over time.

HGB-206: Improvements in Health-Related Quality of Life

Health-related quality of life (HRQoL) findings in Group C patients treated with LentiGlobin for SCD in the HGB-206 study were generated using the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), a validated instrument in SCD.

Data assessing pain intensity experienced by nine Group C patients were analyzed according to baseline pain intensity scores relative to the general population normative value: 2.6 on a scale of 0-10, where 10 equals the most intense pain. Data were assessed at baseline, Month 6 and Month 12.

Of the five patients with baseline scores worse than the population normative value average, four demonstrated clinically meaningful reductions in pain intensity at Month 12; the group had a mean score of 6.0 at baseline and a mean score of 2.4 at Month 12. Of the four patients with better than or near population normative values at baseline, two reported improvement and two remained stable with a mean score of 2.3 at baseline and 0.8 at Month 12.

HGB-206: Group C Safety Results

As of August 20, 2020, the safety data from Group C patients in HGB-206 remain generally consistent with the known side effects of hematopoietic stem cell collection and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to LentiGlobin for SCD. There were no serious AEs related to LentiGlobin for SCD.

One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.

LentiGlobin for SCD Data at ASH

The presentation of HGB-206 Group C results and patient reported outcomes research are now available on demand on the ASH conference website:

About HGB-206

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=32). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: regarding the potential for LentiGlobin for Sickle Cell Disease to treat SCD; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or planned clinical trials; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe...

Shares in Rocket Pharmaceuticals have been living up to their name, shooting up following encouraging early-stage clinical trial results from a gene therapy for a serious inherited rare heart disease.

Results came from a phase 1 trial of RP-A501 for treatment of Danon Disease and sent shares up 75% on the Nasdaq to more than $56, a five-year high.

The surging stock price indicates the markets confidence in gene therapy products after the successful launch of products such as Roche/Spark Therapeutics Luxturna, a gene therapy for a rare inherited eye disease.

Danon Disease is a rare X-linked disorder caused by genetic mutations in the LAMP2 gene and the therapy works by instructing the body to express a healthy copy of the LAMP2B protein in order to correct the condition.

The disease that affects boys and men more severely causes accumulation of autophagosomes tiny structures that cause cells internal structures to break down in the heart muscle and other tissues.

Together with a build-up of glycogen this can lead to severe and frequently fatal degradation of the heart muscle.

RP-A501 could be the first gene therapy for the disease and the early data showed a positive increase in cardiac protein expression.

As of November, three patients have been treated with a low dose of the therapy and two have been treated with a high dose.

An early trial readout showed two patients with LAMP2B expression that was 50% more than normal, measured nine and 12 months after treatment.

A 15%-20% increase could lead to clinically meaningful improvements in cardiac function and the trial reported a 50% decrease in a key biomarker of heart failure.

There was also a reduction in myocardial cell disarray and a visible reduction in autophagic vacuoles, a hallmark of the disease.

The company also noted stabilisation of three other measures a heart failure biomarker known as BNP, plus levels of transaminases and creatine kinase that also indicate skeletal and heart muscle damage.

However one patient who received the highest dose and had a degree of immunity to the adeno-associated virus used in the therapy had an immune reaction classified as a serious adverse event.

Rocket said the event was likely due to complement activation, resulting in reversible thrombocytopenia and acute kidney injury requiring a short round of haemodialysis.

The patient returned to baseline within three weeks and regained normal kidney function.

DrBarry Greenberg, director of the Advanced Heart Failure Treatment Program atUC San Diego Health, Professor of Medicine atUC San Diego School of Medicine, and the principal investigator said: Children with Danon Disease live with a heavy disease burden. Young boys are often severely afflicted.

They show evidence of early onset skeletal muscle weakness and heart disease that can progress rapidly to end-stage with death occurring on the average before age 20. A heart transplant can be performed but is not curative and is associated with its own significant problems.

The results-to-date for this first investigational gene therapy for monogenic heart failure show the potential for direct clinical benefit without emergence of unanticipated side effects of therapy.

The company has also begun a stock offering of $175 million in shares to fund further development following the results.

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Rocket Pharmaceuticals in orbit after gene therapy read-out - - pharmaphorum

bluebird bio has presented long-term data from its Zynteglo one-time gene therapy for the blood disorder beta-thalassaemia, as the company continues talks with payers in Europe to bring the ultra-pricey treatment to market.

The European Medicines Agency (EMA) has granted a conditional marketing authorisation for the drug that will be marketed as Zynteglo (betibeglogene autotemcel), meaning its licence must be renewed each year until confirmatory data is available.

Results announced at the American Society of Hematology could help bluebird make the case for the long-term use of the therapy as the treatment approaches the market in Europe.

In the US, Zynteglo has hit a speed-bump with the FDA, which is asking for more information about production facilities before a review of clinical data can begin.

Of the 10 patients enrolled in the ongoing long-term study (LTF-303) from a phase 3 programme, 9/10 (90%) were transfusion independent (TI) and all these patients remain transfusion independent.

David Davidson, chief medical officer at bluebird, said: All of the patients in our phase 3 studies who achieved transfusion independence have maintained it, with the durability of the treatment effect underscored by patients from our earlier studies reaching their five-year anniversaries of freedom from transfusions.

In a group of patients aged under 18 from the Northstar-2 and Northstar-3 phase 3 studies, 87% (13 out of 15) achieved TI and remained so.

In a long-term follow-up 53% of patients who achieved TI and restarted iron chelation have since stopped and 30% who achieved TI now receive phlebotomy to reduce iron levels.

Davidson added: Transfusion independence has been observed in paediatric, adolescent and adult patients and across genotypes suggesting outcomes with this gene therapy may be consistent regardless of age or genotype.

In Europe bluebird has set a price of up to $1.58 million euros for a single shot.

This is paid in instalments, with 315,000 euros paid up front and four additional payments due only if the treatment continues to be effective.

Zynteglo is already launched in Germany and is nearing the end of its year of free pricing.

But its fair to say that the therapy wont come cheaply even though most member states will likely end up negotiating a lower price.

In England, cost-effectiveness body NICE is reviewing Zynteglo and is due to publish draft document early in the new year.

Although its too early to say how the review will go, NICE will be looking for more certainty on the long-term effects of the therapy.

The latest data wont be part of the submission to NICE, but the company hopes that an ongoing review of the cost-effectiveness bodys methodology will help novel gene therapies get to market.

Nicola Redfern, general manager of bluebird bio UK, is hopeful that NICE will refine its existing Quality Adjusted Life Year (QALY) and find better ways to deal with uncertainties in clinical data.

How we deal with uncertainties is going to be fundamentally important, she said.

Another issue to address is the discount rate NICE uses to calculate the value of medicines and their long-term impact on patients lives.

The 3.5% discount rate currently used means that these benefits reduce quickly over time in the view of NICE and Redfern agrees with NICEs own proposals to adopt the 1.5% discount rate used by the Treasury.

We agree with NICE that there is already evidence to bring it in line with the rate in the Treasury Green Book.

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Bluebird trumpets long-term data from beta-thalassaemia gene therapy - - pharmaphorum

Study results from an open-label, single-dose, multi-center, multinational phase III trial, presented during the late-breaking abstract session of the all-virtual 62nd American Society of Hematology (ASH) Annual Meetings show that etranacogene dezaparvovec (previously known was AAV5-hFIXco-Padua; AMT-061; uniQure/CSL Behring), an investigational gene therapy for hemophilia B, is safe and effective.

The two most common types of hemophilia are hemophilia A, in which patients is lack of clotting Factor VIII, and hemophilia B, caused by a lack of the ability to produce the blood clotting factor IX as the result of an inherited mutation of the gene for factor IX.

Both types of hemophilia can lead to spontaneous and uncontrolled bleeding into muscles, organs, and joints as well as prolonged bleeding following injuries or surgery, which leads to joint deterioration and chronic pain.

Hemophilia B, which accounts for about one-fifth of hemophilia cases.

Clinical trialThe study of etranacogene dezaparvovec recruited adult male patients with severe or moderate-severe hemophilia B.

The results of the study demonstrated that a single administration of the gene therapy etranacogene dezaparvovec led to sustained increases of Factor IX to functionally curative levels capable of eliminating the need for regular infusions to control and prevent bleeding episodes. As a result, most patients were able to stop intensive intravenous regimens. The studys authors believe that the results may open doors for patients previously not included in gene therapy trials.

Blood clotting proteinIn the trial included 52 patients and is the largest and most inclusive hemophilia B gene therapy trial to date. The trial is also the first to include patients with certain immune system markers and found that they did not appear to confer any increased risks, a finding that could significantly broaden the number of patients who may be eligible for gene therapy.

A majority of trial participants (96%) successfully discontinued factor IX replacement therapy after receiving the gene therapy and have been producing their own factor IX for six months. The findings suggest gene therapy could, with a single treatment, give patients the ability to maintain Factor IX levels and reduce or eliminate the need for additional factor IX replacement therapy, according to researchers.

Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life, said senior study author Steven W. Pipe, M.D., of the University of Michigan, Ann Arbor, Michigan, who presented the result of the study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time.

Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life, Pipe added.

Replacement therapyFactor IX replacement therapy can reduce bleeding associated with hemophilia B, but it requires weekly or biweekly infusions to maintain factor IX levels, a burdensome regimen that costs several hundred thousand dollars per year.

In gene therapy, viral particles are used to shuttle engineered genes to cells in the liver. These genes replace the patients faulty factor IX gene, allowing the patients own body to produce factor IX on an ongoing basis. While several gene therapies for hemophilia have shown promise in early phase trials, the study is the first phase III trial to test the approach in a large and diverse array of patients, Pipe said.

Fifty-four patients enrolled in the study; all were dependent on factor IX replacement therapy, and 70% had bleeding episodes in the six months prior to the study despite this prophylactic treatment.

After receiving the etranacogene dezaparvovec gene therapy via a single infusion lasting roughly one hour, factor IX activity increased rapidly from a baseline of up to 2% (moderate to severe hemophilia) to a mean of 37% (very mild hemophilia) at 26 weeks, meeting the trials primary endpoint.

At that level, a patients bleeding risk is essentially the same as someone without hemophilia, Pipe noted.

Seventy-two percent of patients reported no bleeding events in the 26 weeks after receiving the gene therapy.

This tells us that the bleeding phenotype can be corrected through this treatment, which is a remarkable achievement, Pipe said.

Fifteen patients experienced some bleeding, which the researchers indicate is not unexpected given that many of the patients had severely affected joints entering the trial.

What weve seen from patients in the study is that they really dont have to think about their hemophilia anymore. The transformative nature that we hear from the patient stories is, to me, the most important outcome from this study, Pipe said.

Neutralizing antibodiesThe trial is also the first to attempt gene therapy in patients with neutralizing antibodies, a component of the immune system that helps the body fight pathogens. About 40% of trial participants had antibodies to adeno-associated virus serotype 5, or AAV5*, the viral vector used in etranacogene dezaparvovec.

In any other trial protocol, these patients would not have been eligible to participate, Pipe noted.

Previous trials have excluded such patients from gene therapies that use viral vectors under the assumption that antibodies could either block the uptake of the viral vectors in the liver or trigger a dangerous immune response to the therapy. The trial found no evidence of either problem, suggesting neutralizing antibodies do not preclude successful gene therapy.

Two patients did not respond to gene therapy. One did not receive a full dose because the infusion was stopped after the patient showed signs of a reaction to the infusion. The other had a level of neutralizing antibodies about five times higher than any other patient. Since other patients with neutralizing antibodies responded well to the therapy regardless of their level of antibodies, this finding suggests antibodies may pose a problem only at extremely high levels.

No treatment-related serious adverse events were reported. Adverse events were relatively common, occurring in 68% of patients, but most were mild and related to the infusion itself. Nine patients showed evidence of an immune response to the therapy, which was resolved in all cases with a course of corticosteroids.

The researchers will continue to follow patients for five years. Patients will be assessed for sustained factor IX production and effective bleed control over 52 weeks, as well as patient-reported outcome measures to assess the impact on health-related Quality of Life (hrQoL).

Note* Adeno-associated virus serotype 5- (AAV5-) based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials. Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). The investigational agent has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and access to the Priority Medicines (PRIME) regulatory initiative by the European Medicines Agency.

Clinical trialsHOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients NCT03569891

Reference[1] Pipe SW, Recht M, Key NS, Leebeek FWG, Castaman G, Lattimore SU, Van der Valk P, Peerlinck K, et al. LBA-6 First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies [Abstract LBA-6]

Continued here:

ASH 2020: Novel Gene Therapy Found to be Safe and Effective in Treatment of Hemophilia B - OncoZine

Scientists have concluded a Phase 3 trial of a revolutionary gene therapy treating patients with a common form of mitochondrial blindness, and the results surprised them despite treating only one eye, the gene therapy improved vision in both eyes in 78% of participants. The results suggest the treatment is incredibly promising for a condition in which most legally-blind patients would never recover their vision.

Conducted on 37 patients with Leber hereditary optic neuropathy (LHON), the trial involved a gene therapy using a virus vector to modify genes within the patients retinal cells. The results were published in the journal Science Translational Medicine.

LHON affects around 1 in every 50,000 people, with some patients experiencing significant vision loss in a matter of weeks. People affected by the disease will likely lose vision in one eye before subsequent vision loss in the other within 2-3 months. Treatments are limited to visual aids and attempted rehabilitation but have limited success. Typically, just 20% of patients will recover vision and it is extremely rare to recover vision greater than the worst score possible on a standard eye chart (20/200).

As someone who treats these young patients, I get very frustrated about the lack of effective therapies, said senior investigator Dr Sahel, a professor of ophthalmology at the University of Pittsburgh, in a statement.

These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.

The treatment aims at correcting a common mutation within the MT-ND4 gene. MT-ND4 is a core subunit in a protein associated with mitochondria, and a mutation marked m. 11778G>A is thought to be associated with blinding neuropathy. Similarly, mutations in MT-ND4 may also be related to several other brain conditions, although these are not the same as the mutation targeted in this study.

37 patients were injected with the adenovirus-based therapy in one eye and a sham injection (a placebo or, in this case, fake injection) into the other. The trial was randomized and double-blind across multiple centres, which make it the gold-standard of clinical trials. After 48 and 96 weeks, the participants were tested for vision changes and whether they showed signs of improvement using a standard Snellen eye chart (the ones with rows of smaller and smaller letters).

The researchers found that, on average, vision was improved by 15 letters (3 lines on the chart) after 96 weeks, which is an extremely impressive result. However, to the surprise of the researchers, the sham-treated eyes also saw an average improvement of 13 letters. Those that were in the early stages of disease and still losing their vision when they joined the study saw an even better improvement, being able to see 28.5 letters more in the treated eyes on average.

We expected vision to improve in the eyes treated with the gene therapy vector only. Rather unexpectedly, both eyes improved for 78% of patients in the trial following the same trajectory over 2 years of follow-up. Said Dr Yu-Wai-Man, neuro-ophthalmologist at CambridgesDepartment of Clinical Neuroscience.

To decipher how this treatment improved both eyes, the researchers conducted a subsequent study on primates. After injection in the same way as the study above, they found the viral vector was present in cells throughout the eye that was not treated, although the mechanism in which this occurs needs confirmation.The researchers suggest that the viral vector may have transferred across neurones via interocular diffusion, and hence there was an improvement in vision in both eyes.

The results suggest an extremely promising new treatment for a rare but debilitating form of blindness. Further trials are expected to take place to confirm the results, and there are some outstanding limitations of the trial. For example, there was not a control group with this exact mutation, so the researchers could not directly compare to the treatment.

Saving sight with gene therapy is now a reality. The treatment has been shown to be safe and we are currently exploring the optimal therapeutic window. Said Dr Yu-Wai-Man.

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Gene Therapy Unexpectedly Improves Vision In Both Eyes Of Patients Suffering A Form Of Blindness - IFLScience

As the precision medicine field evolves and the science behind personalized therapies for complex conditions surges ahead, reimbursement models are racing to catch up. Precision medicine treatments, like cell and gene therapies, tend to have high price tags and novel delivery mechanisms. This makes creating effective payment models for these therapies a challenge, but drug developers and payers are working together to create out-of-the-box solutions.

Determining prices for breakthrough cell and gene therapies is a complicated process, said Laura Okpala, director of reimbursement policy at Gilead Sciences, at the MedCity INVEST Precision Medicine conference. Though there is a strong belief that the pricing process needs to be driven by value value means different things to different people. Biopharmaceutical companies, like Gilead Sciences, must consult with various stakeholders, including patients, caregivers and payers, who all have different perspectives on value.

Part of why the pricing is so difficult is because of the inherent complexities in the healthcare system, Okpala said. When we think of traditionally how drugs are paid for, were thinking about chronic treatment, were thinking about treatment over a long, extended period, treatment over and over again, reimbursement every single time, and that adds up.

But when you think about cell and gene therapies, all those costs and all of that treatment happens upfront, she added. And then you get that durable response, up to four years at this point. And that is really a paradigm shift when you think about [a] healthcare system that really isnt set up to deal with that upfront cost and that value delivered over time.

But the upfront payment is just one of many challenges. Mark Trusheim, strategic director of the NEWDIGS initiative at the MIT Center for Biomedical Innovation, said at the virtual conference that there are two more key challenges that arise: the performance uncertainty regarding these therapies, particularly around their durability, and the actuarial uncertainty it causes for payers. Most of these therapies are for rare conditions, so a single high-cost therapy in any given month can have a negative impact on payers income statements.

To combat these challenges, several innovative reimbursement models have been developed.

One is a model based on treatment milestones. Per this model, a certain amount of money is paid upfront, and if the therapy doesnt show the intended effects in certain predetermined timeframes, the drug developer pays back a portion of the initial payment.

[The model allows] some risk sharing between the developer and the payer, so they dont have to argue quite so much up front, Trusheim said. And the actual product performance [resolves] how much [is] finally the net reimbursement or the net price for that therapy.

This model helps manage the different expectations and fears of both parties, he added.

Another is a subscription-based model, which includes a fixed fee for unlimited access to certain therapies, Trusheim explained. Cigna has an insurance product that offers this reimbursement model, where plan members contribute a certain amount each month that is used to pay for therapies as needed. Cigna takes on the risk, guaranteeing that they will provide as much therapy as the members require.

This model is a great example of how payers can manage the actuarial fluctuation that occurs when funding cell and gene therapies, Trusheim said. But it comes with its challenges, because in some cases, its difficult to ascertain the eligible population for a particular therapy especially if there are alternate therapies already available.

But Trusheim is confident that innovation in reimbursement will catch up to clinical innovation in the precision medicine arena.

Were now in an era where innovation in payment structures and approaches are beginning to match the kind of innovation we have in the transformative science for patients, he said. Successfully providing patient access and benefit requires both kinds of innovation, not just scientific innovation. The creativity is there we are going to succeed. Just as the science has succeeded, the payment innovation is also moving forward and having success.

Photo credit: Devrimb, Getty Images

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Innovative payment models to support cell and gene therapies on the rise - MedCity News

Dublin, Dec. 08, 2020 (GLOBE NEWSWIRE) -- The "Gene Therapy Global Market Report 2020-30: COVID-19 Growth and Change" report has been added to ResearchAndMarkets.com's offering.

Gene Therapy Global Market Report 2020-30: COVID-19 Growth and Change provides the strategists, marketers and senior management with the critical information they need to assess the global gene therapy market market.

Major players in the gene therapy market are Novartis AG, Bluebird Bio, Inc., Spark Therapeutics, Inc., Audentes Therapeutics, Voyager Therapeutics, Applied Genetic Technologies Corporation, UniQure N.V., Celgene Corporation, Cellectis S.A. and Sangamo Therapeutics.

The global gene therapy market is expected to decline from $3.22 billion in 2019 to $3.18 billion in 2020 at a compound annual growth rate (CAGR) of -1.30%. The decline is mainly due to the COVID-19 outbreak that has led to restrictive containment measures involving social distancing, remote working, and the closure of industries and other commercial activities resulting in operational challenges. The market is then expected to recover and reach $6.84 billion in 2023 at a CAGR of 29.09%.

The gene therapy market consists of sales of gene therapy related services by entities (organizations, sole traders and partnerships) that manufacture gene therapy drugs. Gene therapy is used to replace faulty genes or add new genes to cure disease or improve the body's ability to fight disease. Only goods and services traded between entities or sold to end consumers are included.

North America was the largest region in the gene therapy market in 2019.

The gene therapy market covered in this report is segmented by gene type into antigen; cytokine; suicide gene; others. It is also segmented by vector into viral vector; non-viral vector; others, by application into oncological disorders; rare diseases; cardiovascular diseases; neurological disorders; infectious diseases; others, and by end users into hospitals; homecare; specialty clinics; others.

In December 2019, Roche, a Switzerland-based company, completed its acquisition of Spark Therapeutics for $4.3 billion. With this deal, Roche is expected to strengthen its presence in the gene therapy segment, support transformational therapies and increase its product portfolio. Spark Therapeutics is a US-based company involved in gene therapy.

The high prices of gene therapy medicines are expected to limit the growth of the gene therapy market. The pressure to contain costs and demonstrate value is widespread. Political uncertainty and persistent economic stress in numerous countries are calling into question the sustainability of public health care funding. In less wealthy countries, the lack of cost-effective therapies for cancer and other diseases has influenced the health conditions of the population and has led to a low average life expectancy.

Luxturna, a one-time treatment for acquired retinal eye disease, costs $850,000 in the US and 613,410 in the UK, despite a markdown that is applied through Britain's National Health Service. Zolgensma, for spinal muscular atrophy, is valued at $2.1 million in the US and Zynteglo, which focuses on a rare genetic blood disorder, costs $1.78 million, thus restraining the growth of the market.

The use of machine learning and artificial intelligence is gradually gaining popularity in the gene therapy market. Artificial intelligence (AI) is the simulation of human intelligence in machines, which are programmed to display their natural intelligence. Machine learning is a part of AI.

Machine learning and AI help companies in the gene therapy market to conduct a detailed analysis of all relevant data, provide insights between tumor and immune cell interactions, and offer a more accurate evaluation of tissue samples often conflicted between different evaluators. For instance, since January 2020, GlaxoSmithKline, a pharmaceutical company, has been investing in AI to optimize gene therapy and develop off-the-shelf solutions for patients. It is also expected to reduce turnaround time and also the cost of gene therapies.

Key Topics Covered:

1. Executive Summary

2. Gene Therapy Market Characteristics

3. Gene Therapy Market Size And Growth 3.1. Global Gene Therapy Historic Market, 2015 - 2019, $ Billion 3.1.1. Drivers Of The Market 3.1.2. Restraints On The Market 3.2. Global Gene Therapy Forecast Market, 2019 - 2023F, 2025F, 2030F, $ Billion 3.2.1. Drivers Of The Market 3.2.2. Restraints On the Market

4. Gene Therapy Market Segmentation 4.1. Global Gene Therapy Market, Segmentation By Gene Type, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.2. Global Gene Therapy Market, Segmentation By Vector, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.3. Global Gene Therapy Market, Segmentation By Application, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

4.4. Global Gene Therapy Market, Segmentation By End Users, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

5. Gene Therapy Market Regional And Country Analysis 5.1. Global Gene Therapy Market, Split By Region, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion 5.2. Global Gene Therapy Market, Split By Country, Historic and Forecast, 2015-2019, 2023F, 2025F, 2030F, $ Billion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/y5rj2q

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Global Gene Therapy Market Report 2020: Market is Expected to Recover and Reach $6.84 Billion in 2023 - Forecast to 2030 - GlobeNewswire

Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research

A new review of research bringing together patient, carer and public views of cell and gene therapies has highlighted a need for appropriate education to better inform people including how clinical trials work and the risks and benefits of various treatments.

Over the last decade, new cell, gene and tissue-engineered therapies have been developed to treat various cancers, inherited diseases and some chronic conditions. They offer opportunities for the treatment of disease and injury, to restore function, and in some cases offer cures. In response the NHS Advanced Therapies Treatment Centres (ATTCs) were set up to bring together the health service, academia and industry to address the unique and complex challenges of bringing these therapies to patients.

Led by experts from the Centre for Patient Reported Outcome Research (CPROR) at the University of Birmingham and the Midlands and Wales ATTC (MW-ATTC), the review, funded by a MW-ATTC grant from UK Research and Innovation is the first of its kind and the first to consider both patient and public opinions of cell and gene therapies. Examining 35 studies, the majority of which were published between 2015 and 2020, analysis showed that a lack of understanding of the aims of clinical trials and overestimation of the potential benefits of cell and gene therapy were common among both patients and the general public. Patients were generally of the opinion that more information about participating in clinical trials is vital to enable them to make informed assessment of potential risks and benefits.

Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research and generally, while views of therapies varied among patients, the provision of adequate information increased acceptance.

Interestingly the review also found that patients considered their clinicians to be the most trustworthy source of information which would suggest that patients would approach and discuss these treatments with their physicians. However, researchers found that this might not always be the case due to a number of reasons including the perception that clinicians do not always approve of cell and gene therapies and may try to discourage them from pursuing treatment and may not have enough knowledge of the field to provide adequate advice.

Lead author Dr Olalekan Lee Aiyegbusi, Co-Deputy Director of the Centre for Patient Reported Outcomes Research (CPROR) said: The findings from this research are intended to inform the patient engagement work of the ATTCs. We hope that by highlighting various issues, efforts will be made to correct misconceptions, and improve the awareness of patients and the public about the potential benefits and risks associated with cell and gene therapies.

It is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the ongoing debates. A high level of awareness will also enhance patients ability to make informed decisions about participating in clinical trials and routine administration of cell and gene therapies.

The full paper Patient and public perspectives on cell and gene therapies: a systematic review was published today (Tuesday 8 December 2020) in Nature Communications.

ENDS

For more information please contact Sophie Belcher, Communications Manager, University of Birmingham, on +44 7815607157. Alternatively, contact the Press Office out of hours on +44 (0)7789 921165.

DOI: 10.1038/s41467-020-20096-1.Full paper: http://www.nature.com/ncomms

The University of Birmingham is ranked amongst the worlds top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.

About the Midlands and Wales ATTC (MW-ATTC)

The 9M Midlands and Wales Advanced Therapy Treatment Centre (MW-ATTC) is one of three national Innovate UK funded centres whose goal is to accelerate the delivery of advanced therapies.

It is a regional network spanning the Midlands & Wales comprising a large consortium of industry, healthcare and university partners with expertise in advanced therapy manufacturing including academic and commercial partners, logistics companies, specialists in clinical trial delivery and teams focussed on IT logistics solutions and health economics.

The aim of the MW-ATTC is to enable UK advanced therapy companies to reach the clinical market, whilst simultaneously building clinical capacity regionally to deliver these breakthrough therapies to patients.

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Better education needed to give patients improved understanding of gene therapies, new review highlights - University of Birmingham