Category Archives: Gene therapy

China is predicted to continue its rapid bio growth rates, with more than 10 new mAbs

CPhI Annual Report has launched ahead of the firstCPhI Festival of Pharma(5-16 October 2020), the worlds largest digital pharma Expo that predicts dramatic growth of new mAb production in China, capacity shortages for cell and gene therapies in the USA, and the widespread global adoption of single-use technologies, but only limited continuous bioprocessing.

Three CPhI experts from BioPlan Associates Vicky Qing XIA, Leo Cai Yang and Eric Langer explore the rapidly changing global biologics markets, with special reference to the implications for contract outsourcing and Chinas continued emergence as a hub for both bio innovation and contract services.

Remarkably, China is predicted to continue its rapid bio growth rates, with more than 10 new mAbs predicted to be launched per year in the country by 2025. In fact, the total market size will quadruple by 2025, reaching 120bn RMB, and rising further to 190bn RMB by 2030.

According to the CPhI report, bioprocessing outsourcing in China is currently highly stratified with four tiers and just one domestic company intierone WuXi Biologics and a number of international CDMOs including BI, Lonza and Merck. However, by 2025 it is anticipated that as many as five more domestic CDMOs may have reached tier one status, with FDA and EU facility approvals.

Single Use Systems (SUS) are now far and away the leader at both pre-clinical and clinical stages, with nearly 85% now involving a substantial SUS component. Yet whilst its usage continues to grow, continuous bioprocessing is not anticipated to be in mainstream usage by 2025.

The report also suggested that in the US and Europe there is likely to be a cell and gene therapy capacity crunch by 2025, with CDMOs investing in this area already expanding to try and meet the pipelines demand.

More here:
2025 will see cell & gene therapy capacity shortages in US: CPhI report - BSA bureau

Text size

Pfizer has spent $800 million to build the leading production platform for gene therapies, the company said on Tuesday in its second day of talks to show how it plans to become a fast-growing innovator. Within three years, the drug giant hopes to launch three potential cures for hemophilia and muscular dystrophyworth as much as $4 billion in annual revenue.

We are in an unrivaled position to go to market, said the head of Pfizers rare-disease business, Suneet Varma, in his Tuesday morning presentation. In another Tuesday talk, the companys immunology leaders highlighted coming breakthroughs for the tens of millions who suffer miserable autoimmune skin disorders.

Pfizer (ticker: PFE) is eager to recast itself as a high-multiple growth stock. By year-end, its slower-selling products will be spun off into a business run by Mylan (MYL). From that point, Pfizer thinks it can boost revenue by 6% a year, despite the patent expirations of nearly $20 billion worth of its products in the latter part of this decade. The expected growth will be fired up by 25 product launches, which Pfizer is explaining in two days of online talks.

After rising Monday, Pfizer stock was down 0.3%, at $36.91, in recent trading. The S&P 500 was up 0.4%.

A rare disease may affect only a few hundred thousand people, but there are a lot of these diseases. Cumulatively, they add up to 400 million people worldwide, said Varma, with fewer than 5% having approved treatments. Pfizer believes the rare-disease market will grow at a double-digit annual rate.

Clinical trials are under way for treatments for the bleeding disorders known as hemophilia A and hemophilia B. After treatment, none of the enrolled patients have had bleeding problems, including some in which more than a year has passed since dosing.

Pfizer hopes for approval and launch of its hemophilia B treatment in 2022. Peak annual sales could hit $500 million to $1 billion, says the company. The hemophilia A launch could happen in 2023 and eventually exceed $1 billion in annual sales.

The gene-therapy treatments can require a short hospital stay. But the possibility of a cure will inspire 30% to 40% of hemophilia patients to seek treatment, Pfizer predicts.

A rival in hemophilia A gene therapy, BioMarin Pharmaceutical (BMRN), had a head start over Pfizer in clinical trials. But last month, the U.S. Food and Drug Administration rebuffed BioMarins application for approval and demanded additional follow-up of its patients for a period that will extend through the end of 2021.

The FDA hasnt asked Pfizer to change its design for the hemophilia A trial that the company will begin in a few weeks, said the chief medical officer of the rare-disease unit, Brenda Cooperstone,

There were some worrisome immune reactions among boys in the continuing clinical trial for Pfizers gene therapy for Duchenne muscular dystrophy. But after adjustments in the trials preparatory regime, Pfizer says there have been no more of those events. The treatment showed promising efficacy in early phase trials.

The pivotal Phase 3 muscular dystrophy trial will begin within weeks, with the first data expected in 2022. Pfizer hopes for a launch in 2023 of a muscular dystrophy therapy that would be used by 30,000 people a year in the U.S. and Europe, generating over $2 billion in annual revenue. to reach that goal, Pfizer is racing with Sarepta Therapeutics (SRPT).

In addition to its rare-disease treatments, Pfizer plans to launch four products for autoimmune disorders by 2025. Two of the products would treat atopic dermatitis, which causes painful itching in up to 30 million Americans. Only a portion of those patients get any treatment today.

Based on successful clinical trials, sufferers of the skin disease can look forward to breakthrough treatments, similar to those launched in recent years for psoriasis, says Pfizers inflammation and immunology business head, Richard Blackburn.

Corrections & Amplifications

Pfizers gene-therapy treatments can require short hospital stays. An earlier version of this article incorrectly said the treatments are like bone-marrow transplants, which require months of grueling hospital care.

Write to Bill Alpert at william.alpert@barrons.com

Read the original:
How Pfizer Plans to Lead the Industry in Gene Therapies - Barron's

David Dismuke, Ph.D., joins as Chief Technical Officer, Christopher Shilling as Vice President of Regulatory Affairs and Quality Assurance, and Christina Perry as Vice President of Finance and Operations.All three leaders will be in place in September and join Forge's executive leadership team.

"The addition of David, Chris, and Christina to the Forge leadership team brings immeasurable value to the Forge team and expands our team of gene therapy experts," said Timothy J. Miller, Ph.D., Forge's Co-Founder, President & CEO. "We believe that our accomplished and passionate team, with demonstrated experience in manufacturing and developing gene therapy products, is the foundation of fulfilling our mission to accelerate transformative medicines to reach those who need them most."

David Dismuke joins Forge with more than 15 years of experience in large-scale manufacturing. He is an authority in the bioprocessing and design of gene therapy vectors and has led CMC operations in the large-scale manufacturing of pre-clinical and clinical-grade AAV vectors for more than 10 years. Prior to joining Forge, David was the Vice President of Manufacturing at StrideBio where he directed the development of manufacturing and analytical processes for AAV vectors that utilize novel capsids. In addition, he led the design of therapeutic and reporter transgenes and innovative molecular enhancements to improve AAV production and therapeutic function.He was also previously the Head of Vector Production at Voyager Therapeutics where he led teams in the manufacturing and analytical testing of AAV using the baculovirus/Sf9 production system.Prior to Voyager, David was the Director of the UNC Vector Core, where he oversaw GMP operations as well as the production of research-grade vectors.He earned his PhD from Vanderbilt University, focusing on the molecular biology and lifecycle of HIV-1, and then performed his postdoctoral research at UNC Chapel Hill.

Christopher Shilling joins Forge as Vice President of Regulatory Affairs and Quality. He has over 15 years of experience in development of novel gene therapies for rare and severe disorders. Christopher is an experienced leader in gene therapy regulatory affairs, pharmacology, toxicology, and project management focused on developing strategies for early phase clinical trials in support of a variety of transformative therapeutics for pediatric and rare diseases. Prior to joining Forge, Christopher started the Drug and Device Development program at Nationwide Children's Hospital which was instrumental in gaining acceptance from regulators for over twenty first-in-human gene therapy clinical trials of novel biologic products, a dozen orphan drug designations, and two fast track designations. He received his Bachelor of Science degree in biology and a Master of Science degree in Pathology both from the Ohio State University.

Christina Perry joins Forge Biologics as the Vice President of Finance and Operations. She spent the last several years as the CFO of Drive Capital where she built out all accounting and finance operations, back-office needs, and investor relations and reporting. Christina managed complex entity legal structures and has had extensive exposure to equity and debt financings.Over the last 15+ years Christina has worked with public and private companies and startups across varying industries, developing operational processes to scale with high growth. She began her career at Deloitte, is a licensed CPA in the state of Ohio, earned her Bachelor of Business Administration at the University of Notre Dame and a Master of Accountancy from Miami University.

These additions to the Forge Biologics leadership team continue Forge's momentum within the biotechnology industry in Columbus Ohio, bringing positive impact to both Ohio and the global rare disease community.

About Forge BiologicsThe mission of Forge Biologics is to enable access to life changing gene therapies and help bring them from idea into reality. Forge has a 175,000 ft2 facility in Columbus, Ohio, referred to as "The Hearth", to serve as their headquarters. The Hearth will be home to a custom-designed cGMP facility, dedicated to AAV viral vector manufacturing and will host end-to-end manufacturing services to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing.By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most.

For more information, please visit https://www.forgebiologics.com.

Media Inquiries:Dan SalvoForge Biologics Director of Communications and Community Development[emailprotected]

Business Inquiries:Erandi De Silva, Ph.D.Forge BiologicsCo-Founder and Vice President of Product Development[emailprotected]

SOURCE Forge Biologics

https://forgebiologics.com

See the original post here:
Forge Biologics Strengthens Gene Therapy Leadership with Key Hires in AAV Manufacturing, Regulatory Affairs and Finance to Support Strategic Growth -...

This is paid-for content from our commercial partners.Find out more

Gene therapies are set to revolutionise healthcare by treating diseases at the genetic level. They address the underlying cause of disease and can restore a patient to normal or near normal health. As one-time, personalised treatments, gene therapies have the potential to transform current care pathways by offering eligible patients durable outcomes when successful.

Sponsored by

They offer a one-time intervention, when often the alternative is decades of chronic treatment and monitoring, benefitting both patients and carers. Health and social care systems could also benefit, when complex chronic care regimes can be eliminated or greatly reduced, with significant resources re-deployed across the health and social care system; pertinent in a post-covid-19 world. Of course, gene therapy, as well as the procedure needed to prepare patients to receive it, can have serious side effects and there must be a rigorous assessment of potential risks and benefits to identify the right patients for the treatment.

Additionally, the cost-effectiveness of gene therapies, depends very much on their capacity of delivery health and social savings over a patients lifetime. As many patients treated with gene therapies will be children and young adults, the treatment may deliver additional societal gains over decades.

There are currently over 950 companies worldwide developing Advanced Therapy Medicinal Products, with therapies being tested in 1052 clinical trials, as of Q3 2019.1 Many of these are gene therapies that may become available in the UK over the next five years.

Provision needs to be made urgently for aligned regulatory assessment, health technology appraisal and NHS managed introduction, both in terms of infrastructure as well as reallocated budget. Life science companies also have a responsibility to set value-based prices and should consider alternative payment models and risk share agreements in collaboration with the NHS and government to further ensure value and affordability.

Gene therapies are positive and disruptive technologies that require whole system change to ensure that a post-Brexit NHS is at the forefront of provision rather than lagging behind its European neighbours. There is a window of opportunity for the MHRA with renewed responsibilities in 2021, as well as the National Institute for Health and Care Excellence currently conducting its Methods Review to ensure both regulatory and appraisal systems are aligned for optimal assessment of modern medicines, including gene therapies.

NICEs review of the methods is highly significant as it will set the framework for how England and Wales will provide access to new and breakthrough medicines. Areas of focus should include wider recognition of gene therapies and their benefits, including the one-off treatment offer to patients, gains to the health and social care system, plus pragmatic ways to address inherent lifetime uncertainty.

Crucially, for paediatric and young adult patients, there is an additional challenge the NICE methods review needs to resolve. High economic discount rates used in the health economic assessment process by NICE has a prejudicial impact on the cost-effectiveness of treatments that are intended to offer benefits over decades, such as gene therapies. This issue can be easily addressed if Treasury guidance for utilising lower discount rates is adopted.

A successful NICE Methods Review would ensure that the UK has a fit-for-purpose medicines assessment process. This will help to achieve world-leading status for bringing new medicines such as gene therapy to patients and will sustain UK-based research and development investment. This should be prioritised as the end of the EU exit transition period approaches, to ensure the governments vision of a vibrant post-Brexit economy, fuelled by science and technology, allows the UK to lead the world in healthcare innovation.

1. Alliance for Regenerative Medicine. Quarterly regenerative medicine sector report Q3. 2019. Available at: https://alliancerm.org/?smd_process_download=1&download_id=5556 [Accessed 11 February 2020].

The rest is here:
Gene Therapy will the NHS lead or follow? - Health Service Journal

BOSTON, Sept. 15, 2020 /PRNewswire/ --GreenLight Bioscienceshas received a $3.3 million grant from the Bill & Melinda Gates Foundation to develop new mRNA-based gene therapies for Sickle Cell Disease and other global health challenges.

The funding will support GreenLight's research and testing of affordable therapies using the company's novel messenger RNA (mRNA) approach to gene editing. mRNA technology is already being used to develop vaccine candidates for infectious diseases, including the COVID-19 pandemic.

While initial research will focus on a cure for Sickle Cell Disease, GreenLight plans to develop a versatile gene editing platform to address a variety of diseases affecting underserved patient populations, such as treating HIV in developing countries.

Sickle Cell Disease is a group of inherited blood disorders in which red blood cells develop abnormally, causing pain and anemia. More than 4 million people currently suffer from the disease, with another 40+ million having the sickle cell trait, which can be passed on to future generations. The disease primarily targets people of African, Hispanic, or Middle Eastern descent. Current treatment regimens including blood transfusions and bone marrow transplants are costly, invasive, and impractical for treating large segments of affected patient populations.

"Funders are recognizing the potential of our innovative approach to gene editing that, in combination with our proprietary RNA manufacturing capability, has the potential to deliver accessible gene therapies and improve human health globally," said Marta Ortega-Valle, senior vice president of Human Health and Corporate Development at GreenLight Biosciences. "Finding a safe and effective therapy is critical, but equally important is the ability to produce it affordably for broader access. We are grateful for the Gates Foundation's support to advance novel gene editing approaches for populations in which those therapies are currently out of reach."

Gene editing therapies hold significant promise in the treatment of Sickle Cell Disease since it is a disorder caused by gene mutation. Using RNA as its core, GreenLight Biosciences is working to develop an in vivo gene therapy that could ultimately offer a cure to the disease.

Once the therapy candidate is validated and moves into clinical use, GreenLight Biosciences' biomanufacturing platform will accelerate production of affordable treatments at scale. "Manufacturing sufficient quantities of high-quality RNA at an accessible cost is critical for achieving the full potential of new therapies that aim to reach a global patient population. That capability does not yet exist in the market, but GreenLight's end-to-end, self-contained manufacturing platform aims to make that possible for all mRNA-based therapies and vaccines," Ortega-Valle added.

About GreenLight Biosciences, Inc.GreenLight is a bio-performance company with a unique, cell-free production platform that delivers high-performing RNA solutions to human, plant and animal challenges. GreenLight develops RNA products for plant and life science applications, and collaborates with industry leaders to advance vaccine development, pandemic preparation, crop management, and plant protection. The cutting-edge, natural platform delivers higher-quality RNA at a lower cost and higher speed than was ever before possible. The GreenLight team values diversity, inclusion, and equality and promises to use collaboration to remain scientifically imaginative and passionately focused on making a difference in the world. For more information, visithttps://www.greenlightbiosciences.com/.

SOURCE GreenLight Biosciences

Go here to read the rest:
GreenLight Biosciences Receives $3.3 Million Grant to Develop Sickle Cell Disease Cure Using mRNA Gene Therapy - PRNewswire

Helixmith said Wednesday that it has submitted a phase 3-3 extension study protocol of its gene therapy Engensis (VM202) for diabetic peripheral neuropathy (DPN), to the U.S. Food and Drug Administration.

The company set a one-year follow-up period to confirm the pain reduction and safety of VM202 in treating DPN. DPN is one of the most common complications of diabetic diseases. About 30 million Americans have diabetes, and 28.5 percent of them develop DPN. Among the DPN patients, 40 to 50 percent experience painful symptoms.

The study's primary endpoint is the average pain reduction effect measured and recorded in the pain diary over the last week of the sixth month from the first injection.

The study will be carried out with patients who had not taken Gabapentinoids, such as Pregabalin and Gabapentine, in 15 research laboratories across the U.S., including Northwestern University in Chicago.

"Existing painkillers for DPN patients are not a fundamental treatment for the disease as they only relieved pain while often accompanying serious side effects and high addiction," Helixmith CEO Kim Sun-young said. "We will try our best for the success of phase 3-3 clinical trials as well as the ongoing phase 3-2 study."

FDA recognized the clinical results of Engennsis and designated it as an advanced regenerative medicine advanced therapy (RMAT) in 2018, the company said. RMAT is a new system designed to speed up the development and approval of innovative regenerative therapies. It gives special privileges of the U.S. fast track and priority or accelerated screening.

Read more here:
Helixmith eyeing P3-3 clinical trials of gene therapy Engensis - Korea Biomedical Review

Advanced Therapy Medicinal Products Market Research Report by Therapy Type (CAR-T Therapy, Cell Therapy, Gene Therapy, and Tissue Engineered Product) - Global Forecast to 2025 - Cumulative Impact of COVID-19

New York, Sept. 18, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Advanced Therapy Medicinal Products Market Research Report by Therapy Type - Global Forecast to 2025 - Cumulative Impact of COVID-19" - https://www.reportlinker.com/p05953100/?utm_source=GNW

The Global Advanced Therapy Medicinal Products Market is expected to grow from USD 2,946.38 Million in 2019 to USD 6,524.94 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 14.16%.

Market Segmentation & Coverage:This research report categorizes the Advanced Therapy Medicinal Products to forecast the revenues and analyze the trends in each of the following sub-markets:

Based on Therapy Type , the Advanced Therapy Medicinal Products Market studied across CAR-T Therapy, Cell Therapy, Gene Therapy, and Tissue Engineered Product. The Cell Therapy further studied across Non-stem Cell Therapy and Stem Cell Therapy.

Based on Geography, the Advanced Therapy Medicinal Products Market studied across Americas, Asia-Pacific, and Europe, Middle East & Africa. The Americas region surveyed across Argentina, Brazil, Canada, Mexico, and United States. The Asia-Pacific region surveyed across Australia, China, India, Indonesia, Japan, Malaysia, Philippines, South Korea, and Thailand. The Europe, Middle East & Africa region surveyed across France, Germany, Italy, Netherlands, Qatar, Russia, Saudi Arabia, South Africa, Spain, United Arab Emirates, and United Kingdom.

Company Usability Profiles:The report deeply explores the recent significant developments by the leading vendors and innovation profiles in the Global Advanced Therapy Medicinal Products Market including AveXis, Inc., Bluebird Bio, Inc., Celgene Corporation, Gilead Lifesciences, Inc., JCR Pharmaceuticals Co., Ltd., Kolon TissueGene, Inc., MEDIPOST, Novartis AG, Organogenesis Inc., PHARMICELL Co., Ltd, Spark Therapeutics, Inc., UniQure N.V., and Vericel Corporation.

FPNV Positioning Matrix:The FPNV Positioning Matrix evaluates and categorizes the vendors in the Advanced Therapy Medicinal Products Market on the basis of Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape.

Competitive Strategic Window:The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies. The Competitive Strategic Window helps the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. During a forecast period, it defines the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth.

Cumulative Impact of COVID-19:COVID-19 is an incomparable global public health emergency that has affected almost every industry, so for and, the long-term effects projected to impact the industry growth during the forecast period. Our ongoing research amplifies our research framework to ensure the inclusion of underlaying COVID-19 issues and potential paths forward. The report is delivering insights on COVID-19 considering the changes in consumer behavior and demand, purchasing patterns, re-routing of the supply chain, dynamics of current market forces, and the significant interventions of governments. The updated study provides insights, analysis, estimations, and forecast, considering the COVID-19 impact on the market.

The report provides insights on the following pointers:1. Market Penetration: Provides comprehensive information on the market offered by the key players2. Market Development: Provides in-depth information about lucrative emerging markets and analyzes the markets3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, and manufacturing capabilities of the leading players5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and new product developments

The report answers questions such as:1. What is the market size and forecast of the Global Advanced Therapy Medicinal Products Market?2. What are the inhibiting factors and impact of COVID-19 shaping the Global Advanced Therapy Medicinal Products Market during the forecast period?3. Which are the products/segments/applications/areas to invest in over the forecast period in the Global Advanced Therapy Medicinal Products Market?4. What is the competitive strategic window for opportunities in the Global Advanced Therapy Medicinal Products Market?5. What are the technology trends and regulatory frameworks in the Global Advanced Therapy Medicinal Products Market?6. What are the modes and strategic moves considered suitable for entering the Global Advanced Therapy Medicinal Products Market?Read the full report: https://www.reportlinker.com/p05953100/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

__________________________

Original post:
Advanced Therapy Medicinal Products Market Research Report by Therapy Type - Global Forecast to 2025 - Cumulative Impact of COVID-19 - Yahoo Finance...

BEDFORD, Mass., Sept. 18, 2020 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today participation and presentations at the following virtual conferences:

The live webcast presentations from the Oppenheimer and Chardan conferences will be accessible on Homologys website in the Investors section, and the webcast replays will be available on the website for 90 days following the presentations. For on-demand webcasts from the Cell & Gene Meeting on the Mesa conference, please visit http://www.meetingonthemesa.com for full information.

About Homology Medicines, Inc. Homology Medicines is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

See the rest here:
Homology Medicines to Participate in Upcoming Conferences - GlobeNewswire

The European Medicines Agency is on the verge of releasing revised guidance for advanced therapy medicinal products containing genetically modified cells, which includes chimeric antigen receptor (CAR)-T cell therapies.

The Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells was originally issued in 2012 but underwent revision and consultation from July 2018-July 2019. The revised version is expected to be adopted in October and published in November, according to Ana Hidalgo-Simon, MD, PhD, head of advanced therapies at EMA. She previewed the major changes at RAPS Convergence 2020.

There were an enormous number of comments on the document, Hidalgo-Simon said.The agency is also working on a Q&A document on principles of good manufacturing practices (GMP) for Advanced Therapy Medicinal Products (ATMP) starting material. There will likely be consultation on the document in 2021, she said. (RELATED: Regulation of advanced therapy medicinal products in the EU, Regulatory Focus, 16 July 2020.)

Major changesEMA chose to update the guidance to reflect the increase in clinical experience with these therapies, particularly chimeric antigen receptor-T (CAR-T) cells; to cover new categories of products, such as induced pluripotent stem (iPS) cells; and to allow for consideration of new tools for genetic modification of cells, such as genome editing technologies, she said.

The main quality updates are related to starting materials, the manufacturing process, and characterization and release. For example, the starting materials guidance will now include genome editing tools, while the manufacturing process includes a new section on comparability. The characterization and release portion of the guidance includes specific advice for CAR-T cells.

Additionally, the guidance calls for dose-finding studies to explore safety, toxicity, and anti-tumor activity at different dose levels, to define the threshold dose required for anti-tumor effect, and to define the recommended dose or range for Phase 2 studies. She said sponsors need to show a solid rationale for the criteria being used to find the dose.

The guidance also calls for Phase 3 confirmatory trials to follow a randomized controlled design, comparing the CAR-T cell therapy to a reference regimen, unless otherwise scientifically justified. Single-arm studies will continue to be allowed, but they will be the exception, Dr. Hidalgo-Simon said.

Be very careful with the design of the trials, she advised. The assumptions need to be really, very well backed.

When it comes to safety, the guidance calls for a 15-year follow period. While sponsors wont have all the answers at the time of submission, Hidalgo-Simon said they should have a plan that includes monitoring during the post-authorization period.

Hidalgo-Simon also advised sponsors to think beyond the approval process and consider what evidence will be needed to convince other stakeholders -- from patients to payers -- about the safety and efficacy of the therapy.

Avoiding development pitfallsRichard Dennett, PhD, the senior director of chemistry, manufacturing and controls regulatory affairs at PPD, also participated in the RAPS Convergence 2020 session on advanced therapies. He reviewed development points where companies can run into trouble with advanced therapies, particularly CAR-T cell products.Dennett recommended that product sponsors keep the end in mind when developing advanced therapies by focusing on the target product profile at the beginning of development. That profile includes the indication for which approval will be sought and the incidence of that indication; other considerations include mode of action, demographics, how much of the product needs to be produced, and market access and reimbursement considerations.

He also outlined several areas where developers should focus to create a watertight regulatory package, including sufficient product characterization, potency assay, impurities, formulation, stability, lack of sufficient development batches, and validation strategy.

Dennett urged developers to dive into the growing number of regulatory guidance documents for advanced therapies. In addition to the European guidance documents, developers should consultthe US Food and Drug Administrations Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), which was released in January 2020. (RELATED: Advanced therapies: Trip hazards on the development pathway, Regulatory Focus, 02 August 2020)

Live and breathe the guidances that are out there, Dennett advised. They allow us to understand what expectations we need to meet.

The key to success in advancing CAR-T cell therapies is the mitigation of risk, Dennett said: The biggest risk is the one that you havent thought of.RAPS 2020 Convergence

See the original post:
Convergence: EMA close to finalizing guidance for advanced therapies - Regulatory Focus

The CDC estimates that sickle cell disease affects well over 100,000 Americans, with the disease occurring most often in African Americans. September has been designated as National Sickle Cell Awareness month designed to focus attention on the ongoing research in this field and the need for new treatments. The sector can certainly point to the significant progress that has taken place during the past few years, with new medicines reaching the market and several novel therapeutics with new mechanisms of action advancing in the pipeline.

Ted Love, president and CEO of Global Blood Therapeutics Inc. (GBT), said 2019 was a landmark year with the FDA approval of two new novel therapies to treat sickle cell disease. He was speaking at the virtual annual Sickle Cell Disease (SCD) Therapeutics Conference this week. His company, together with the Sickle Cell Disease Association of America, was hosting the one-day event featuring discussions on the latest advances and future trends.

Approvals

The key manifestation of the inherited blood disorder is that red blood cells (RBCs) are abnormally shaped (crescent), which restricts their flow in blood vessels and limits oxygen delivery to the bodys tissues, leading to severe pain and organ damage. The condition is also characterized by severe chronic inflammation that results in vaso-occlusive crisis (VOC) where patients experience episodes of extreme pain and organ damage.

Late November, GBT gained accelerated approval for its Oxbryta (voxelotor) tablets for the treatment SCD in adults and pediatric patients 12 and older. The agencys green light came less than two weeks after it gave the go-ahead to Novartis AG for Adakveo (crizanlizumab) to reduce the frequency of VOCs in adult and pediatric patients ages 16 and older with SCD.

According to Love, Oxbryta is a new class of therapy binding to hemoglobin and stabilizing RBCs in an oxygenated state and inhibiting deoxygenated sickle hemoglobin polymerization, making cells less likely to bind together and form the distinctive sickle shape.

The launch of the drug has gone well since it was approved, he said in the companys second-quarter financial report and business update, despite the impact of COVID-19. Net sales in the period reached $31.5 million, well ahead of the Streets expectations. Going forward, the company is planning to expand the potential use of Oxbryta for the treatment of SCD in children as young as 4 years old and also seek marketing authorization in Europe for Oxbryta to treat hemolytic anemia in SCD patients ages 12 and older with a marketing authorization application being submitted to the EMA by the middle of next year.

Pipeline progress

Cambridge, Mass.-based Agios Pharmaceuticals Inc. is working on mitapivat (AG-348), an investigational, oral, small-molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes, in patients with SCD. The compound has been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and increase adenosine triphosphate (ATP), and through that mechanism, it may reduce hemoglobin (Hb) S polymerization and red blood cell sickling. In June, the company reported that clinical proof of concept had been established based on a preliminary analysis in a phase I trial being conducted in collaboration with the U.S. NIH as part of a cooperative research and development agreement.

The ongoing study had enrolled nine patients, with eight completing all planned dose levels of mitapivat. Seven of eight patients who completed all dose levels experienced a Hb increase, with five of eight patients (63%) achieving a hemoglobin increase of 1 g/dL from baseline (range 1-2.7 g/dL). All five patients who achieved a hemoglobin increase of 1 g/dL did so at doses of 50 mg BID or lower. Decreases in 2,3-DPG and increases in ATP levels were observed, consistent with the proposed mechanism of action and comparable to that observed in healthy volunteer studies with mitapivat.

The company said it expects to report data from ACTIVATE and ACTIVATE-T, its two global pivotal trials for mitapivat in adults with pyruvate kinase deficiency, between the end of 2020 and mid-2021.

Watertown, Mass.-based Forma Therapeutics Holdings Inc., which made its public debut this year, also has a selective RBC pyruvate kinase-R activator in its pipeline for treating SCD. FT-4202 is being evaluated in a phase I trial in SCD patients ages 12 and older and has been granted fast track, rare pediatric and orphan drug designations. The compound is a potent activator of pyruvate kinase-R designed to improve RBC metabolism, function and survival by decreasing 2,3 DPG and increasing ATP, potentially resulting in both increased hemoglobin levels and reduced VOCs.

Olinciguat, an oral guanylate cyclase (sGC) stimulator, being developed by Cyclerion Therapeutics Inc., has completed the treatment period in its STRONG-SCD study with a total of 70 patients randomized. The placebo-controlled, dose-ranging study is designed to evaluate safety, tolerability and pharmacokinetics, as well as to explore effects on daily symptoms and biomarkers of disease activity when dosed over a 12-week treatment period. Top-line results are expected this year. Olinciguat is a compound that aims to stimulate sGC production, leading to the production of a signaling molecule called cyclic guanosine monophosphate (cGMP). High levels of cGMP help reduce inflammation in blood vessels, decrease adhesion between RBCs, and allow for improved blood flow by increasing the availability of nitric oxide.

Boston-based Imara Inc. is developing IMR-687, a small-molecule inhibitor of PDE9 that degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology. The company said that lower levels of cGMP are often found in people with SCD and beta-thalassemia and are associated with impaired blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide-mediated vasodilation. Blocking PDE9 acts to increase cGMP levels, which are associated with reactivation of fetal hemoglobin.

In August, the company dosed the first patient in its Ardent phase IIb trial of IMR-687 for adult patients with SCD. The planned primary efficacy objective is to evaluate the proportion of all patients with fetal hemoglobin (HbF) response, defined as an increase of 3% in HbF from baseline to week 24, compared to placebo.

Gene therapy/gene editing

Since SCD is a monogenic disease condition, researchers believe that it would be a good candidate for gene therapy therapeutic approaches. For example, significant progress is being made by Cambridge, Mass.-based Bluebird Bio Inc. with lentiglobin, its lentiviral-based gene therapy that inserts an anti-sickling beta-globin variant into CD34-positive cells, progenitors of red blood cells.

At the virtual European Hematology Association (EHA) meeting in June, it reported new data from its ongoing phase I/II study involving adult and adolescent patients with SCD that showed a near-complete reduction of serious VOCs and acute chest syndrome. The company expects to submit a BLA to the FDA for the gene therapy next year.

Crispr Therapeutics AG and Vertex Pharmaceuticals Inc. are progressing CTX-001, an investigational, autologous, CRISPR/Cas9 gene-edited hematopoietic stem cell therapy being evaluated for patients suffering from severe hemoglobinopathies. At EHA, the companies reported that in the phase I/II Climb-121 study, at nine months after CTX-001 infusion, the first treated patient was free of VOCs, was transfusion independent and had total hemoglobin levels of 11.8 g/dL, 46.1% fetal hemoglobin and F-cells (erythrocytes expressing fetal hemoglobin) of 99.7%.

Last month, Cambridge, Mass.-based Editas Medicine Inc., a genome editing company, reported that the FDA had granted rare pediatric disease designation for EDIT-301, an experimental, autologous cell medicine, being developed as a potentially best-in-class, durable medicine for SCD. The company plans to file an investigational new drug application for EDIT-301 by the end of this year. EDIT-301 comprises sickle patient CD34+ cells genetically modified using a hCRISPR/Cas12a (also known as Cpf1) ribonucleoprotein to edit the HBG1/2 promoter region in the beta-globin locus. Red blood cells derived from EDIT-301 CD34+ cells demonstrate a sustained increase in fetal hemoglobin (HbF) production.

In its second-quarter financial report and business update, Beam Therapeutics Inc. announced the nomination of its first two adenine base editing development candidates, BEAM-101, targeting patients with hereditary persistence of fetal hemoglobin, and BEAM-102 (Makassar variant), both aimed at correcting SCD.

New Initiative

The NIH, which reports it spends approximately $100 million on sickle cell disease research, announced that is has launched The Cure Sickle Cell Initiative designed to speed the development of cures for the disease. It will take advantage of the latest genetic discoveries and technological advances to progress the most promising genetic-based curative therapies safely into clinical trials within five to 10 years.

Aided by research partners, the initiative will establish a national data warehouse of genetic therapies for sickle cell disease and conduct comparative analyses of therapeutic approaches to assess both clinical and cost effectiveness. National networks will also be created to make it easier for patients and providers to interact with the research, clinical trials, and other activities.

Excerpt from:
New medicines in the pipeline to treat sickle cell disease - BioWorld Online