FDA outlines new path for bespoke therapies

The U.S. FDA has expressed its commitment to bespoke, personalized therapies by outlining a novel path to market entry, known as the plausible mechanism pathway, for products where a randomized trial is not feasible.

In an article published in the New England Journal of Medicine, FDA Commissioner Martin Makary and CBER director Vinay Prasad used the story of Baby K.J. — the infant with urea cycle disorder who was treated with the world’s first personalized CRISPR gene editing drug product — to define the plausible mechanism pathway. They outlined several conditions of the new framework:

• The pathway will be used for diseases for which the biologic cause is known rather than diseases defined by a constellation of clinical findings or dozens of unclear genomewide associations
• The situation must involve the development of a medical product that targets the underlying or proximate biological alterations
• The must be a well-characterized natural history of the disease in the untreated population
• The agency must see confirmation that the target was successfully drugged, edited or both
• There must be a demonstrated improvement in clinical outcomes or course; in conditions with progressive deterioration, consistent improvements will be viewed favorably by the FDA

The FDA will prioritize rare diseases, particularly those that are fatal or associated with severe disability in childhood, but the plausible mechanism pathway will be also available for common diseases, particularly diseases for which there is considerable unmet need.

The article ended with the assertion that existing FDA pathways are not enough address bespoke, transformative therapies. “Unfortunately, the FDA has heard from patients, parents, researchers, clinicians, and developers that current regulations are onerous and unnecessarily demanding, provide unclear patient protection, and stifle innovation. We share this view.”