The United States Food and Drug Administration (FDA) recently released a draft guidance, Expedited Program for Serious Conditions — Accelerated Approval of Drugs and Biologics. Accelerated approval allows drugs for serious conditions that fill an unmet medical need to be approved by the FDA based on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.
The guidance “addresses the accelerated approval process, including granting accelerated approval (e.g., discussion of endpoints, evidentiary criteria, confirmatory trials and other conditions of accelerated approval), and withdrawal of accelerated approval.” There are some changes from the 2014 final guidance, including changes to early consultation on novel endpoints, timely conduct of confirmatory trials, other aspects of confirmatory trials, and the expedited withdrawal of accelerated approval.
Under the Consolidated Appropriations Act of 2023, Congress mandated that the FDA update conditions that sponsors who use the accelerated pathway must follow, including requiring confirmatory trials by the date that the drug is granted accelerated approval. Additional conditions may be set on confirmatory trials, including enrollment targets, an agreed-upon study protocol, and certain milestones. The FDA also stated that it would stipulate conditions for post approval studies no later than the date that the drug is granted accelerated approval, potentially including details such as enrollment targets, the final study protocol deadline, and certain milestones.
The guidance further noted that the agency will not consider granting accelerated approval to a drug if it is not feasible to complete an adequate and well-controlled trial to determine clinical benefits. “FDA may require that post approval studies be underway prior to accelerated approval or within a specified time from the date of accelerated approval,” said FDA. “The INDICATIONS AND USAGE section of drug labeling must include a succinct description of the limitations of usefulness of the drug and any uncertainty about anticipated clinical benefits, with reference to the CLINICAL STUDIES section for a discussion of this available evidence.”
The guidance states that sponsors must submit copies of all promotional materials to the FDA within certain time frames and provide reports of the progress of their post approval studies roughly every 180 months, which the agency will publish.
As has been encouraged in prior guidance documents, the FDA encouraged sponsors to communicate with the agency early to determine whether they may be eligible for accelerated approval, to discuss surrogate or intermediate clinical endpoints, to review clinical trial design, and plan for confirmatory trials. Along those lines, FDA noted that the agency “will strive to provide a timely response to a sponsor’s inquiry regarding a development program intending to seek accelerated approval, and it is equally important that a sponsor responds promptly to FDA’s inquiries.”
Upon finalization of the draft, this guidance will replace the accelerated approval-related content in the final guidance for industry entitled “Expedited Programs for Serious Conditions—Drugs and Biologics” issued on May 30, 2014 (the 2014 final guidance). Additional programs to expedite product development are covered in the 2014 final guidance as well as other guidances.