For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new
drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel
therapeutics to treat
rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat
cancer and
infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel
surrogate endpoint. The application of AA to
rare diseases requires more predictability to drive greater access to appropriate use of AA for more
rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing
biomarker endpoints to enhance the development of novel
therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in
drug development and
rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in
rare disease programs; 2) Implementing a
Biomarker Qualification Request Process to provide the opportunity for an early determination of
biomarker acceptance; and 3) A proposed scientific framework for qualifying
biomarkers as primary endpoints. The paper's final section highlights case studies of successful examples that have incorporated
biomarker endpoints into FDA approvals for
rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction.