New Year, New Accelerated Approval

When sponsor companies (i.e., applicants) are granted Accelerated Approval (AA) by the U.S. Food and Drug Administration (FDA), this regulatory pathway allows for earlier approval of drugs that treat serious conditions, generally provide a meaningful advantage over available therapies, and address an unmet medical need based on a surrogate endpoint. The use of a surrogate endpoint can considerably shorten the time to receive approval from the FDA. A surrogate endpoint is a marker that is reasonably likely to predict clinical benefit but is not itself a measure of clinical benefit.

Sponsors are still required to conduct studies to confirm the anticipated clinical benefit in their confirmatory study. If the study does prove clinical benefit, approval will change from accelerated to regular approval. The confirmatory study, a cornerstone of AA, is arguably the most controversial aspect of this regulatory pathway as sponsors must verify trial results from their pivotal study in a post-approval Phase 3 or Phase 4 study. While some sponsors have ignored FDA’s expectation that the confirmatory study must be well underway, if not fully enrolled, at the time of a product’s AA granting, FDA is not lenient with their confirmatory study timeline expectations.

With the Food and Drug Omnibus Reform Act (FDORA) signed by President Biden on 29 December 2022, Congress has now given FDA the power to require that confirmatory studies are initiated before a sponsor receives AA. Consequently, sponsors could expect a delay in their New Drug Application (NDA) or Biologics License Application (BLA) submission if they don’t abide by this new regulatory requirement. FDORA also established an AA oversight council, with FDA representatives from the Center of Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and the Oncology Center of Excellence (OCE) to “ensure the consistent and appropriate use” of AA across the Agency. 

Additional new modernizations to AA require:

• Sponsors to provide status updates to the FDA on any required post-approval study, starting six months after approval and every six months thereafter until the study is completed
• Codified expedited procedures FDA may use in withdrawing approval if the confirmatory study fails to verify the product’s clinical benefit
• FDA to specify the conditions for a post-approval study no later than the date of product approval
• FDA to publish a rationale any time a post-approval study for a product approved under AA is not required

The FDA will draft a new dedicated guidance document on AA to be issued within 18 months after enactment of FDORA to include topics such as the use of surrogate or intermediate clinical endpoints (including novel endpoints), use of novel clinical trial designs, and expedited procedures that FDA may use to withdraw approval of an AA product.

However, these AA reforms don’t go far enough to address a regulatory loophole that can derail a company’s path to AA. Sponsors must demonstrate their drug is better than the best available therapy at the time of receiving an AA, but products that are granted AA do not count as available therapy. This is the biggest pitfall of this loophole. The best available therapy can change at any time during an NDA or BLA review if a competitor’s product converts from AA to regular approval, or if a new product receives regular approval. To level the playing field for AA, it seems much more appropriate for FDA to “lock in” the best available therapy at the time a sponsor’s NDA or BLA is accepted for filing. This will ensure that important new medicines, which address an unmet medical need, are not pushed away due to a timing technicality.

The bottom line is that it is critical for sponsors to discuss their AA pathway with FDA early and frequently during the drug development process, which includes agreement on the trial design of the confirmatory study that should be ongoing by the time a product receives AA. We also must emphasize the importance of keeping a pulse on competitive intelligence to stay well-informed of the competitive landscape for products in the same indication so that NDA or BLA applications are not forced to be withdrawn due to a regulatory gap in the AA process.

Halloran’s regulatory team offers deep-rooted expertise and experience with marketing applications, special designations, health authority meetings, and due diligence. Contact a member of our team today to discuss your most pressing regulatory challenges.