OIn 2022, 54% of FDA new drug approvals were for rare diseases, a significant increase in proportion of approvals in the recent years. At the town hall, Dr. Melanie Blank, a primary reviewer at the FDA’s Center for Drug Evaluation and Research’s (CDER) Division of cardiovascular and renal products, highlighted this saying, “We are seeing one or two new applications coming in every week for new gene therapies for different diseases.”
One of the issues raised at the meeting was the often contrasting need for extensive efficacy data associated with gene therapies with the limitations of small patient populations and disease variability found with rare diseases, which leaves sponsors in a difficult predicament. Dr. Elizabeth Hart, branch chief of Division of Clinical Evaluation and Pharmacology/Toxicology (DCEPT) said, “No product development will be the same…. but in general, when feasible, we recommend from an efficacy perspective, that clinical trials are designed to demonstrate clinically meaningful effects in how patients feel, function or survive.”
At the FDA town hall, leaders discussed the difficulties of having solely paediatric patient populations in some rare disease gene therapy trials. Blank acknowledged that in many cases, an exclusively paediatric patient population could lead to difficulties with drawing consent for early phase trials. Still, Blank suggested that companies enroll the patient population that is most likely to benefit, because early phase studies contain the most safety risks.
Furthermore, due to smaller patient populations, rare disease trials are often smaller in size than other disease trials. Dr. Lei Xu, chief of the General Medicine Branch 2 in the FDA’s DCEPT, said this is a dilemma as more permanent treatments like gene therapies come to the regulator that often “require substantial evidence of effectiveness from adequate and well controlled clinical studies”. In such cases, data derived from patients outside of the clinical study can serve as external controls.
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