Gene therapies for the treatment of hemophilia - How the FDA supports pharmaceutical companies

Tue, 2018 / 08 / 28

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Ihr Ansprechpartner Prof. Matthias P. Schönermark, M.D., Ph.D.

Prof. Matthias P. Schönermark, M.D., Ph.D.
Founder and Managing Director

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Last month, the Center for Biologics Evaluation and Research of the U.S. FDA published several new guidances for the industry, providing information and recommendations regarding cellular and gene therapies. The new draft guidance “Human Gene Therapy for Hemophilia”, amongst others, provides recommendations on how to design clinical trials for testing efficacy and safety of gene therapies for the treatment of hemophilia A and B. Hemophilia A, the most common type, results from deficiency of the coagulation factor VIII, while hemophilia B results from deficiency of factor IX. So far, only symptomatic therapies for hemophilia exist. Although effective treatments are available, they still involve lifelong injections to prevent bleeding. Gene therapy for the treatment of hemophilia may provide long-term expression of the missing or abnormal coagulation factor VIII and IX in hemophilia patients, thereby representing an appealing alternative to current factor replacement therapies while overcoming the development of neutralizing antibodies as the most severe adverse event of factor replacement therapy.

To act compliant to regulatory needs and for general advice, stakeholders and sponsors of investigational new drugs, such as gene therapeutic products, are encouraged to already make use of the opportunities early in the development process of a therapy, which are offered by the FDA for regulatory advice. This new draft guidance yet addresses key considerations in terms of the development program of preclinical as well as human clinical studies. With respect to clinical trials to evaluate the effectiveness of hemophilia products, the FDA herein gives recommendations regarding appropriate i) efficacy endpoints, ii) the study design and iii) study population, iv) statistical considerations, v) study monitoring and vi) patient experience. Further detailed information on preclinical and clinical studies in general are available in a separate guidance document. In recent years, gene therapies have increasingly been in the public spotlight and five gene therapies have already been approved by the FDA and the EMA for commercial use. The release of several new draft guidances highlights once more the high actuality and the increasing interest in innovative therapies such as gene therapies. In the field of hemophilia, there are roughly 19 gene therapies (recruitment status: not yet recruiting, recruiting, enrolling, active, completed) registered in ClinicalTrials.gov for the treatment of hemophilia A or B, with three of them being phase III trials sponsored by BioMarin Pharmaceutical or UniQure Biopharma.

In our latest White Paper "Successful Market Access for Gene Therapies", we described and discussed the key strategic aspects that will become relevant with the approaching market launch of gene therapy products. In addition, possible solutions to unresolved problems, such as cost-bearers and pricing, are presented. We would be happy to provide you with our exclusive white paper on request.

BY Prof. Matthias P. Schönermark, M.D., Ph.D., managing director and Dr. Alexandra Kuhn

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