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Recently, Dr. Scott Gottlieb, the US FDA’s director, issued a statement announcing that the FDA will continue to vigorously promote the development of gene therapy and released six new guidelines.

Gene therapy was once a theory and has now become a therapeutic reality for patients. Gene therapy has the potential to treat and cure some refractory diseases. The FDA’s policy framework for how genetic product development, regulatory review and reimbursement will help lay the foundation for continued growth in this new market. Last year, we released a draft framework for regenerative medicine, mentioning several ways to accelerate development, such as breakthrough therapy identification and advanced therapy for regenerative medicine (RMAT), which may be applicable to the development of gene therapy. Today, the FDA has introduced a complementary framework for the development, review and approval of gene therapies.

In the past 12 months, the FDA has approved three gene therapy products. This reflects the rapid development of the field. We have reached an inflection point that reliably delivers gene cassettes to the body, cells and human body. In the future, we expect this area to continue to move forward, and there may be many gene therapies for the treatment of debilitating diseases. These therapies have great hopes. Our new initiatives are designed to promote this area of ​​innovation.

Gene therapy is being researched in many disease areas, including genetic diseases, autoimmune diseases, heart disease, cancer and AIDS. We look forward to working with academia and the research community to provide safe and effective products for more patients. But we know that we still need to understand how genetic products work, how to use them safely, and whether they can continue to work in the body without long-term side effects. The more challenging problems with gene therapy compared to traditional drug reviews are product manufacturing and quality, or long-lasting response, which is often not fully answered in any reasonable size pre-marketing trial. When approving some genetic products, we may need to accept some uncertainty about these issues. For example, in some cases, it is not known at the time of approval whether it is valid for a long time. Effective tools for reliable post-marketing tracking, such as the required post-marketing clinical trials, will be key to driving the development of gene therapy and helping to ensure safe and innovative therapies.

Even if there is uncertainty, we need to ensure patient safety and fully describe the potential risks of genetic products and prove their benefits. The original goal of genetic products was to treat devastating diseases, many of which lacked treatment, including some deadly diseases. In the absence of available therapies, the FDA has always been willing to accept more uncertainty in order to get promising therapies in a timely manner. In this case, the drug sponsor usually requires a post-marketing clinical trial called a phase 4 clinical trial to confirm the clinical benefit of the drug. This is the power that Congress gives to the FDA, such as the implementation of accelerated approval.

When it comes to new technologies such as gene therapy, the FDA will keep up with the times to ensure the unique challenges of adapting to these new technology platforms. Today, we are taking a step towards shaping the regulatory structure of modern gene therapy. The FDA plans to release a set of six scientific guidance documents as a cornerstone of a comprehensive regulatory framework to help us advance the field of gene therapy while ensuring that new products meet the FDA’s gold standard for safety and efficacy.

3 specific disease gene therapy guidelines

Today, we have released three new guidelines for the development of gene therapy products for specific diseases. This is the first three specific disease guidelines issued by the FDA for gene therapy products.

Human gene therapy for hemophilia: The hemophilia gene therapy product currently under development as a single treatment can cause patients to produce long-term missing or abnormal clotting factors in the body, reducing or eliminating the need for clotting factor substitutes. To determine the correct development path for these products, the FDA has published a draft guidance on gene therapy products that are targeted to the treatment of hemophilia. Once finalized, this new guide will provide recommendations for clinical trial design and preclinical considerations to support the development of these gene therapy products. Among other elements, the draft guide provides recommendations for alternative endpoints for accelerated approval of gene therapy products for the treatment of hemophilia.

Human Gene Therapy for Retinal Diseases: Another popular area is gene therapy products for the treatment of retinal diseases. The FDA also plans to publish the Human Gene Therapy for Retinal Disorders guidance. Gene therapy products currently undergoing clinical trials of retinal diseases in the United States are usually intravitreal or subretinal. In some cases, the gene therapy product is encapsulated in a device to be implanted into the eye. This new guide will focus on specific issues in gene therapy for retinal diseases, providing recommendations for product development, preclinical testing, and clinical trial design.

Human gene therapy for rare diseases: In the United States, diseases with fewer than 200,000 patients are called rare diseases. The National Institutes of Health reports that nearly 7,000 rare diseases affect more than 25 million Americans. About 80% of rare diseases are caused by single gene defects, and about half of rare diseases affect children. Since most rare diseases do not have approved treatments, there are significant unmet needs. Once the finalization of the Human Gene Therapy for Rare Diseases guidance, recommendations for preclinical, manufacturing, and clinical trial design will be provided. This information is intended to help sponsors design clinical development plans, which may have limited potential population and potential safety and safety issues, as well as issues that explain effectiveness.

3 guideline updates for gene therapy manufacturing

Today, we have also provided a comprehensive update of three existing guidelines to address manufacturing issues related to gene therapy.

The first guide, Chemistry, Manufacturing and Control (CMC) Information for New Gene Applications (INDs) for Human Gene Therapy Research, on how the sponsor provides sufficient CMC information to ensure the safety, uniformity, and Recommendations for quality, purity and efficacy. This guide applies to human gene therapy, as well as products containing human gene therapy in combination with drugs or devices.

The second guide, “Retroviral Testing for Retroviral Vector Gene Therapy Products During Product Manufacturing and Patient Follow-up,” provides for retroviral vector-based gene therapy products, as well as for accepting reversals More recommendations for correct testing of RCR during follow-up monitoring of patients with viral gene delivery gene therapy products. Specifically, the guide recommends identifying the materials and quantities that need to be tested. The guide also provides recommendations for general test methods.

The third guide, Long-Term Follow-up after Human Gene Therapy Drug Delivery, provides recommendations for design long-term follow-up (LTFU) observational studies to collect data on delayed adverse events after administration of gene therapy products. Some of the additional uncertainties inherent in new technology platforms such as gene therapy – including those related to the persistence of treatment effects, and the fact that genes can be off-target in theory if inserted incorrectly – therefore, need to be listed Focus on long-term follow-up of patients. This guide describes product characteristics, patient-related factors, preclinical and clinical data that should be considered when assessing the need for long-term follow-up. The guide also describes the characteristics of effective post-marketing follow-up.

Once finalized, these draft guidelines will replace the earlier versions of the FDA’s guidelines issued in April 2008 (CMC) and November 2006 (RCR and LTFU).

Gene therapy promises to bring efficiency and even cure to many refractory diseases. Some of these genetic products will almost certainly change the paradigm of medical practice and the fate of patients with certain diseases.

The FDA’s goal is to help these innovative therapies develop within the framework of ensuring safety and effectiveness and continue to build confidence in this emerging medical arena.

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