In December 2024, the U.S. Food and Drug Administration (FDA) released a new draft guidance titled “Expedited Program for Serious Conditions – Accelerated Approval of Drugs and Biologics.” This guidance aims to streamline the review process, expedite the development of innovative therapies, and enable them to meet patient needs more quickly and effectively. Additionally, the guidance clearly defines the eligibility criteria for accelerated approval and outlines application requirements.
Key Information from the Guidance
Scope of Application
The Accelerated Approval program facilitates faster FDA approval for drugs treating serious or life-threatening conditions, such as rare diseases, cancers, or infectious diseases, where existing treatment options are inadequate or fail to meet patient needs. It is especially relevant for diseases with long course or clinical outcomes that are challenging to assess in the short term. The program uses surrogate or intermediate clinical endpoints to expedite approval, focusing on key concepts such as serious conditions, available therapies, and unmet medical needs.
Requirements for Accelerated Approval Application
- Risks and Considerations
Accelerated approval speeds up market entry but depends on limited trial data, posing risks like unidentified side effects or unverified clinical benefits. To mitigate these risks, FDA requires post-approval confirmatory trials. If these trials fail to confirm benefits, approval may be withdrawn.
- Accelerated Approval Endpoints
1. Surrogate Endpoints
A surrogate endpoint is generally a biomarker, that is thought to predict clinical benefit but is not itself a measure of clinical benefit. Examples:
- Sputum culture conversion from positive to negative during treatment of pulmonary tuberculosis.
- The reduction of liver inflammation or fibrosis has been considered reasonably likely to predict long-term clinical benefit in noncirrhotic nonalcoholic steatohepatitis (NASH).
- The reduction in iron stores has been considered reasonably likely to predict a decrease in transfusion-related adverse events caused by iron overload in thalassemia.
2. Intermediate Clinical Endpoints
An intermediate clinical endpoint is a measurement of a therapeutic effect that can be measured earlier than an effect on irreversible morbidity or mortality (IMM). Examples:
- In a chronic disease, short-term benefit (e.g., initial improvements in functional impairment) may be considered reasonably likely to predict a longer duration of effect.
- A treatment for active cerebral adrenoleukodystrophy in boys aged 4–17 was approved based on major functional disability-free (MFD-free) survival at 24 months following first neurologic functional score ≥ 1. This therapy received accelerated approval with a requirement for post-marketing studies to confirm long-term MFD-Free survival.
