Daily Archives: May 14, 2020

On May 8, the Food and Drug Administration (FDA) granted accelerated approval of Retevmo (selpercatinib), the first RET inhibitor, for people with non-small-cell lung cancer (NSCLC) and two types of thyroid cancer with specific genetic mutations.

Innovations in gene-specific therapies continue to advance the practice of medicine at a rapid pace and offer options to patients who previously had few, Richard Pazdur, MD, director of the FDAs Oncology Center of Excellence, said in a press release.

Retevmo, from Eli Lilly and companywhich obtained the drug, then known as LOXO-292, when it acquired Loxo Oncology last yearis a selective inhibitor of a receptor tyrosine kinase known as RET. This enzyme plays a role in cell proliferation, and mutations or fusions in the RET gene can drive cancer development. RET alterations are rare overall, occurring in less that 1% of all cancers and 2% of NSCLC, but they are more frequent in certain cancer types.

Although Retevmo is considered a pancancer, or site-agnostic, therapy that works against cancers with a specific genetic alteration anywhere in the body, last weeks FDA approval is more limited. Retevmo is indicated for adults with metastatic RET fusion-positive NSCLC and for adults and adolescents (age 12 and up) with advanced or metastatic RET fusion-positive thyroid cancer or advanced or metastatic RET-mutant medullary thyroid cancer. Medullary thyroid cancer, which involves a specific type of cell, is uncommonaccounting for only 4% of all thyroid cancersbut it frequently has RET mutations.

The accelerated approval was based on promising findings from the Phase I/II LIBRETTO-001 trial. Study results were previously presented at the 2018 American Society of Clinical Oncology annual meeting,the 2019 World Conference on Lung Cancerand the 2019 European Society for Medical Oncology Congress.

LIBRETTO-001 enrolled people with NSCLC, thyroid cancer and a variety of other solid tumors with RET mutations or fusions. Both previously treated patients and those starting systemic treatment for the first time were eligible. Everyone was treated with Retevmo, taken as a pill twice daily; there was no placebo group.

Retevmo led to an overall response ratemeaning complete or partial tumor shrinkagein 64% of the 105 previously treated people with NSCLC, rising to 85% for the 39 patients new to treatment. The mediation duration of response was 17.5 months for the treatment-experienced group, and was not reached in the newly treated group because a majority were still responding.

When he presented preliminary study findings last year, Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York City, noted that Retevmo appeared particularly active against cancer that had spread to the brain. Ten of the 11 people with brain metastasis (91%) experienced shrinkage of cancer in the brain, including 18% with complete remission.

In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases, Drilon said in a Lilly press release. The approval of selpercatinib marks an important milestone in the treatment of NSCLC, makingRET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy.

Looking at the participants with thyroid cancer, the overall response rate was 69% for the 55 treatment-experienced patients and 73% for the 88 previously untreated people with RET-mutant medullary thyroid tumors. Here, the duration of response was 22.0 months for the previously untreated group and not reached for the treatment-experienced group. In the smaller subset of 19 previously treated and eight newly treated people with RET fusion-positive thyroid cancer, the overall response rates were 79% and 100%, respectively. Response duration was 18.4 months in the former group and not reached in the latter group.

RETalterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers, saidLori Wirth, MD, of Massachusetts General Hospital Cancer Center. For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibitsRET.

Treatment with Retevmo was generally safe and well tolerated, with just 5% of participants stopping treatment because of adverse events. The most common adverse reactions include diarrhea, constipation, dry mouth, fatigue, swelling, rash, high blood pressure, elevated ALT and AST liver enzymes, elevated glucose, cholesterol and creatinine, and various other laboratory test abnormalities.

The product label for Retevmo includes warnings about several potential serious side effects: liver toxicity, severe high blood pressure, bleeding, heart rhythm abnormalities, hypersensitivity reactions and slow wound healing. Retevmo can cause fetal harm if used during pregnancy.

A Lilly spokesperson told FiercePharma that Retevmo would be available from specialty pharmacies within a week at a list price of about $20,600 for a 30-day supply.

Drugs that receive accelerated approval based on response rates in early studies are expected to undergo further testing in larger randomized trials to confirm clinical benefits such as improved survival, and the FDAcan rescind approval if they dont measure up. Two Phase III trials, Libretto-431 for NSCLC (ClinicalTrials.gov number NCT04194944) and Libretto-531 for medullary thyroid cancer (ClinicalTrials.gov number NCT04211337), are currently underway.

Another investigational RET inhibitor, Blueprint Medicines pralsetinib (formerly known as BLU-667) has also demonstrated good activity in an early study, with overall response rates of 60% for NSCLC patients who used prior platinum-based chemotherapy and 71% for previously untreated people.

The availability of RET inhibitors underscores the need for genetic testing to determine which patients have gene mutations or fusions that could make them eligible for these new targeted therapies. Next-generation sequencing of a tumor tissue biopsy sample or liquid biopsy using a blood sample can reveal multiple actionable genetic alterations. However, there is currently no FDA-approved companion test specifically for RET alterations.

Increasingly, through the use of comprehensive biomarker testing, patients with metastatic cancer have an opportunity to receive a treatment tailored to the specific genomic nature of their tumor, Andrea Ferris, president and chief executive officer of LUNGevity, said in the Lilly press release. We urge patients to ask their doctors about broad biomarker tests that includeRETalterations.

Click here for full prescribing information for Retevmo.

Click here to learn more about lung cancer.

Click here to learn more about thyroid cancer.

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FDA Approves RET Inhibitor Retevmo for Lung and Thyroid Cancer - Cancer Health Treatment News

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

The cell-based markets was analyzed for 2018, and projected to 2028. The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair as well as diabetes mellitus will be other major markets.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 309 of these are profiled in part II of the report along with tabulation of 302 alliances. Of these companies, 170 are involved in stem cells.

Profiles of 72 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 67 Tables and 25 Figures. The bibliography contains 1,200 selected references, which are cited in the text.

This report contains information on the following:

The report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. Role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. Current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

Key Topics Covered

Part I: Technologies, Ethics & Regulations

Executive Summary

1. Introduction to Cell Therapy

2. Cell Therapy Technologies

3. Stem Cells

4. Clinical Applications of Cell Therapy

5. Cell Therapy for Cardiovascular Disorders

6. Cell Therapy for Cancer

7. Cell Therapy for Neurological Disorders

8. Ethical, Legal and Political Aspects of Cell therapy

9. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions

10. Markets and Future Prospects for Cell Therapy

11. Companies Involved in Cell Therapy

12. Academic Institutions

13. References

For more information about this report visit https://www.researchandmarkets.com/r/7h12ne

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The Cell Therapy Industry to 2028: Global Market & Technology Analysis, Company Profiles of 309 Players (170 Involved in Stem Cells) -...

PLYMOUTH MEETING, Pa., May 14, 2020 /PRNewswire/ -- INOVIO (NASDAQ: INO) today announced that 85 percent (44 out of 52) of patients newly diagnosed with the deadly brain cancer glioblastoma multiforme (GBM) who received the company's DNA medicine INO-5401, in combination with INO-9012 and PD-1 inhibitor Libtayo (cemiplimab), were alive for at least 12 months or more (overall survival at 12 months: OS12) following treatment. These data will be featured at an oral poster presentation at the ASCO 2020 Virtual Scientific Program, May 29-31, 2020.

GBM is the most common and aggressive type of brain cancer. Currently, the median overall survival with standard of care therapy, which includes radiation and chemotherapy (temozolomide: TMZ), is approximately 15 to 22 months.

The Phase 1/2 clinical trial demonstrated that 84.4% percent (27 of 32) of patients with MGMT promoter unmethylated tumors, and 85% (17 of 20) of patients with MGMT promoter methylated tumors were alive at 12 months. This promising clinical result is coupled with a robust immunological response to all three cancer antigens in INO-5401, including human telomerase (hTERT), Wilms Tumor-1 (WT-1) and prostate specific membrane antigen (PSMA). Activated, cytotoxic T cells directed towards these cancer antigens commonly expressed on GBM tumors were detected in all patients tested to date and continue to support the immunogenic potential of INOVIO's DNA medicines. Importantly, INO-5401 + INO-9012 was safe and well-tolerated when given not only with radiation and TMZ, but also with PD-1 inhibition with Libtayo, which is being jointly developed by Regeneron and Sanofi. These results are being presented in a virtual format at the 2020 Annual ASCO meeting (Abstract #2514).

Dr. David Reardon, Clinical Director, Center for Neuro-Oncology of Dana-Farber Cancer Institute and coordinating principal investigator of GBM-001 said, "Although these data are preliminary, and follow-up remains early, this novel combination of a cancer antigen-specific, T cell generating DNA medicine with a PD-1 inhibitor is exciting and may overcome more than 20 years of a standard of care that has proven sub-optimal for our patients with GBM. A tolerable, new combination of medicines utilizing a novel mechanism of action, such as that provided by INO-5401 and INO-9012 with cemiplimab, is very welcome for this hard-to-treat brain cancer, especially when shown to be tolerable with standards such as radiation and chemotherapy, and when demonstrating the immunogenicity seen in the GBM-001 study."

Dr. J. Joseph Kim, INOVIO's President & CEO, said, "While we recognize these data are early, we are very excited to see robust immunogenicity and the potential for extending survival, coupled with a clear ability to be able to combine not only with the standard of care, but with a checkpoint inhibitor, Libtayo. Where others have failed with single-agent checkpoint inhibition in GBM, our DNA medicine combined with Libtayo and standard of care has demonstrated clear immunogenicity and the potential to extend overall survival."

In a previous announcement, INOVIO reported key interim data from the 52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter methylated patients and 75% (24 of 32) unmethylated patients were progression-free at six months (PFS6) measured from the time of their first dose, exceeding historical standard-of-care data.

This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested an acceptable safety profile consistent with that of Libtayo and INOVIO's platform technology. The majority of patients tested had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401. Immune responses to all three tumor-associated antigens were demonstrated in this study. INOVIO plans to report 18-month overall survival data later this year.

Study Design

The trial was designed to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There are two cohorts in this trial. Cohort A includes 32 participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B includes 20 participants with a tumor with a MGMT methylated promoter. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and temozolomide (TMZ). Interim data presented here and at SITC was obtained as of October 2019 and overall survival data at 18 months is expected in Q4 2020. For more information of the clinical study, see http://www.clinicaltrials.gov, identifier NCT03491683.

Poster Details

Abstract/Poster 2514Poster Discussion Session: Central Nervous System TumorsThe ASCO 2020 Virtual Scientific Program runs from May 29 -31.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 to 22 months and the median progression-free survival is approximately 7 months. In the U.S., the estimated annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.

About INO-5401 and INO-9012

INO-5401 encodes for INOVIO's SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.

About INOVIO's DNA Medicines Platform

INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with MERS and COVID-19 diseases being developed under grants from the Coalition for Epidemic Preparedness Innovations (CEPI). DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body.

INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO's proprietary hand-held smart device called CELLECTRA. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. Administration with the CELLECTRA device ensures that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response. INOVIO's DNA medicines do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured, the stability of the products which do not require freezing in storage and transport, and the robust immune response, safety profile, and tolerability that have been demonstrated in clinical trials.

With more than 2,000 patients receiving INOVIO investigational DNA medicines in more than 6,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.

About INOVIO

INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to protect and treat people from infectious diseases, cancer, and diseases associated with HPV. INOVIO is the first and only company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to produce a robust and tolerable immune response. Specifically, INOVIO's lead candidate VGX-3100, currently in Phase 3 trials for precancerous cervical dysplasia, destroyed and cleared high-risk HPV 16 and 18 in a Phase 2b clinical trial. High-risk HPV is responsible for 70% of cervical cancer, 91% of anal cancer, and 69% of vulvar cancer. Also in development are programs targeting HPV-related cancers and a rare HPV-related disease, recurrent respiratory papillomatosis (RRP); non-HPV-related cancers glioblastoma multiforme (GBM) and prostate cancer; as well as externally funded infectious disease DNA vaccine development programs in Zika, Lassa fever, Ebola, HIV, and coronaviruses associated with MERS and COVID-19 diseases. Partners and collaborators include Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense Advanced Research Projects Agency (DARPA)/Department of Defense (DOD), GeneOne Life Science/VGXI, HIV Vaccines Trial Network, International Vaccine Institute (IVI), Medical CBRN Defense Consortium (MCDC), National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics, Roche/Genentech, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. INOVIO also is a proud recipient of 2020 Women on Boards "W" designation recognizing companies with more than 20% women on their board of directors. For more information, visit http://www.inovio.com.

CONTACTS:

Media: Jeff Richardson, 267-440-4211, jrichardson@inovio.comInvestors: Ben Matone, 484-362-0076, ben.matone@inovio.com

This press release contains certain forward-looking statements relating to our business, including our plans to develop DNA medicines, our expectations regarding our research and development programs, including the planned initiation and conduct of preclinical studies and clinical trials, and the availability and timing of data from those studies and trials. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or our collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resourcesthat may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2020 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured or commercialized, that final results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.

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INOVIO's INO-5401 in Combination with PD-1 Inhibitor Libtayo (cemiplimab) Demonstrates 85% of Newly Diagnosed Glioblastoma Patients Are Alive 12...

MedicalResearch.com Interview with:

MedicalResearch.com: What is the background for this study?

Response: More than 40% of women withhormone receptor-positive, HER2-negative early-stage breast cancer have high recurrence scores (RS)of 26-30. Optimal adjuvant systemic therapy in this subgroup remains unclear, and national guidelinescurrently recommendeither chemoendocrine therapy or endocrine therapy alone.In addition, the difference in overall survival of a patient with a RS 26-30 versus RS >30 is unclear.

MedicalResearch.com: What are the main findings?

Response: Our main findings are:

1) Chemotherapy improves outcomes for those with RS 26-30,

(2) RS >30 carries a worse prognosis for survival compared to RS 26-30 despite receiving chemoendocrine therapy, and

(3) The magnitude of chemotherapy benefit appears to be similar between those with RS 26-30 and RS >30.

MedicalResearch.com: What should readers take away from your report?

Response: Breast cancer patients with a 21-gene recurrence score of 26 or higher are a heterogeneous group of patients with different prognosis and outcomes, and chemotherapy may benefit patients with recurrence scores of 26-30.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Further prospective studies are needed to investigate optimal adjuvant therapy regimens for patients with a high 21-gene recurrence score

No relevant disclosures

Citation:

Ma SJ, Oladeru OT, Singh AK. Association of Adjuvant Chemotherapy With Overall Survival in Patients With Early-Stage Breast Cancer and 21-Gene Recurrence Scores of 26 or Higher.JAMA Netw Open.2020;3(5):e203876. doi:10.1001/jamanetworkopen.2020.3876

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765371

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21-Gene Recurrence Scores of 26 or Higher Can Help Determine If Chemotherapy Will Be Effective - MedicalResearch.com