FDA Releases Six Draft Guidances Related to Gene Therapy

On Wednesday, July 11^th, FDA released six draft guidances to aid in the development of new gene therapies. Of the six guidances, three were disease specific and three were related to manufacturing.

Disease Specific Guidance Documents

Human Gene Therapy for Hemophilia

The first disease specific guidance relates to gene therapy (GT) products for the treatment of hemophilia, and is intended to provide sponsors with information regarding the development of these products. According to a recent statement by Scott Gottlieb, M.D., Commissioner of the FDA, “this new guidance will provide recommendations on the FDA’s current thinking on clinical trial design and preclinical considerations to support the development of these gene therapy products […] The draft guidance provides recommendations regarding surrogate endpoints that could be used by sponsors pursuing accelerated approval of gene therapy products that are intended for treatment of hemophilia.”

Human Gene Therapy for Retinal Disorders

The purpose of the second draft guidance is to provide information for sponsors interested in developing gene therapies for adult and pediatric populations suffering from retinal disorders. Retinal disorders can be age or genetics related, and often include central or peripheral vision impairment and progressive vision loss. The Agency’s guidance document offers recommendations related to product development, preclinical testing, and clinical trial design for these therapies.

Human Gene Therapy for Rare Diseases

The final disease-specific draft guidance provides sponsors with information concerning the development of GT products for the treatment of rare diseases in adult and pediatric populations. Rare diseases are those that affect less than 200,000 people in the United States. Often, these diseases have no FDA-approved treatments, so there is a significant unmet need for these products. According to a statement from the Agency, “once finalized, [the guidance] will provide recommendations on preclinical, manufacturing and clinical trial design for all phases of the clinical development program for these types of gene therapies. The information is intended to assist sponsors in the design of clinical development programs, where there may be limited study population size, potential feasibility and safety issues, as well as issues relating to the interpretation of effectiveness.”

FDA Updates Guidance Documents for Gene Therapy Manufacturing

In addition to the three new disease-specific draft guidance documents, the FDA also updated three existing guidance documents for the manufacturing of human gene therapies. Once finalized, these new guidances will replace older guidance documents, which were issued in 2006 (RCR and LTFU) and 2008 (CMC).

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

This 54-page draft guidance provides sponsors of human gene therapy products with CMC information for investigational new drug applications (INDs). “The purpose of this draft guidance is to inform sponsors how to provide sufficient CMC information required to assure product safety, identity, quality, purity, and strength (including potency) of the investigational product.” This draft guidance applies to gene therapy products as well as drug/device combination products that contain a human gene therapy.

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up

This updated draft guidance provides recommendations for sponsors of vector-based human gene therapy products. Due to the disease-causing capacity of replication competent retrovirus (RCR), vigilant testing is required to ensure that RCR is not present in vector-based human gene therapy products. This guidance provides information on follow-up monitoring of patients and advice regarding general testing methods.

Long Term Follow-Up After Administration of Human Gene Therapy Products

This final draft guidance provides sponsors with information regarding design protocol for long-term follow-up (LTFU) studies on delayed adverse events. According to a recent statement from the FDA, “this guidance describes product characteristics, patient-related factors, and the preclinical and clinical data that should be considered when assessing the need for LTFU observations and describes the features related to effective post-market follow up.”

Gene therapy is a largely experimental technique that has progressed rapidly in the last ten years. It is a promising treatment option, particularly for serious diseases that do not have other approved treatment options. However, there are still many unknowns, and FDA’s goal is to use these updated guidance documents to promote the safe and effective development of new human gene therapy treatments.

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