The Food and Drug Administration has created new mechanisms to accelerate market access for investigational therapies targeting rare diseases, according to a June 8 article. However, experts say these pathways remain undefined in ways that leave important questions unanswered about their impact.
Last year, the FDA introduced the plausible mechanism pathway and rare disease evidence principles (RDEP), both aimed at expediting drug development for rare conditions. These initiatives join several established programs such as Fast Track designation, Breakthrough Therapy designation, priority review, and others that have been developed over more than three decades to support drug candidates addressing unmet medical needs.
Eva Temkin, partner at Arnold & Porter who advises biopharma companies on regulatory matters, said in an email that sponsors should consider these newer pathways as complementary rather than substitutes or alternatives. Temkin described the plausible mechanism pathway as a “very narrow construct under which specific types of evidence may be considered sufficient under a specified set of circumstances.” She contrasted this with traditional expedited programs that focus on broader programmatic considerations like agency interactions and review timelines.
During a recent FDA workshop discussing implementation of the plausible mechanism guidelines, Gene Therapy CMC Branch Chief Anna Kwilas clarified that the program serves as a framework for achieving approval of applicable products rather than constituting a new approval pathway. Despite clear differences between old and new initiatives at a high level, many details remain unresolved. Temkin noted ongoing legal and regulatory questions regarding postmarketing obligations under the draft guidance for the plausible mechanism pathway, and pointed out uncertainties related to commercial impacts such as regulatory exclusivities and incentives for drugs approved using data described in the framework guidance.
Other programs available to rare disease developers include Commissioner’s National Priority Voucher pilot program—which shortens review times for products aligned with national priorities—platform technology designation allowing reuse of certain information across submissions after initial approval, accelerated approval based on surrogate endpoints since 1992, orphan drug designation offering tax credits and market exclusivity since 1983, regenerative medicine advanced therapy designation from 2016 supporting cell and gene therapies' expedited review process; fast track (since 1997) provides frequent engagement with FDA; breakthrough therapy (since 2012) offers intensive guidance; priority review grants speedier reviews within six months; and rare pediatric disease priority review voucher reauthorized in February allows faster reviews or can be sold by companies.
With multiple options available but many details yet unclear about some recent additions—particularly around evidentiary requirements—industry leaders continue seeking further clarification from regulators.
