FDA’s New Accelerated Approval Draft Guidance

Louis Cicchini, PhD, director, scientific affairs, cell and gene therapy, Cencora

Cori Gorman, PhD, senior director, biopharmaceutical CMC and regulatory affairs, Cencora

The FDA’s latest draft guidance on accelerated approval for new drugs, “Expedited Program for Serious Conditions—Accelerated Approval of Drugs and Biologics,” is a game-changer for biopharmaceutical companies hoping to bring life-saving treatments to market. If you’re navigating the commercialization process for innovative therapies, particularly in the rare disease space, this evolving pathway demands your attention.

The accelerated approval (AA) program aims to fast-track the development and approval of breakthrough drugs for serious or life-threatening conditions with unmet medical needs, especially in rare diseases and oncology. The updated guidance¹ offers unprecedented clarity on eligibility and evidentiary requirements and clinical endpoint expectations—empowering biopharma companies to expedite market entry for critical drugs.

Success, however, in this program hinges on strategic decision-making. Identifying appropriate endpoints; selecting the right FDA division (the Centers for Biologics Evaluation and Research for biologics, including cell and gene therapies [CGTs], or the Center for Drug Evaluation and Research for conventional pharmaceuticals); and understanding the critical quality attributes (CQAs) for your product are crucial to avoiding costly and time-consuming missteps.

A roadmap for success

To make informed decisions before submitting an AA request, it’s critical to have a roadmap in place.

First, you must show a clear understanding of clinical endpoints. Conditional approval can be granted based on intermediate or surrogate clinical endpoints, which are tailored to the specific product being evaluated. The FDA evaluates CQAs, which are essential for assessing the safety and efficacy of innovative therapies. CQAs for CGTs and biologics differ due to the drug or drug candidate’s unique manufacturing processes and therapeutic applications. CQAs ensure a drug consistently achieves the desired effects, linking to the reliability of endpoints used in the AA process.

A strong understanding of a drug candidate’s CQAs enhances confidence in the predictability of clinical benefits derived from these endpoints. Predicting clinical benefit is a key requirement for approval under the AA pathway. To this end, FDA describes two broad categories of appropriate endpoints:

• Surrogate endpoints are measurable markers that may predict clinical benefit but do not directly measure it. Examples include tumor shrinkage, biomarker expression, and therapeutic transgene expression.
• Intermediate endpoints directly measure the intended therapeutic effect and are reasonably likely to predict clinical benefit. Some examples may include overall response rate and clinical improvement scores.

A strong link between CQAs and surrogate and intermediate endpoints can increase confidence in the drug’s clinical benefits, supporting the AA pathway.

In the area of CAR T therapies, T-cell viability, functionality, and CAR expression levels serve as potency indicators, directly correlating to the overall response rate. In gene therapy, the effectiveness of viral vector transduction and transgene expression should align with therapeutic benefits assessed through surrogate endpoints.

A thorough understanding of your disease model is essential for defining these endpoints and linking potency measures to clinical outcomes.

Second, it’s important to start confirmatory trials early in the AA process to facilitate quicker regulatory decisions and faster patient access to effective treatments. These trials are vital, as they provide evidence for a drug candidate’s clinical benefits and help secure full regulatory approval.

If the confirmatory trial fails to demonstrate efficacy, the drug may be withdrawn from the market. For example, a new cancer treatment might be granted AA based on its ability to shrink tumors in early trials (a surrogate endpoint), but a confirmatory trial would need to show improved overall survival to confirm its clinical benefit.

Finally, it’s critical to navigate the withdrawal risks. Approval under AA is conditional. The FDA can revoke it if you fail to deliver on post-approval commitments, misrepresent data, face safety concerns, or other issues. To mitigate risks, it’s important to align endpoints with CQAs from the outset, plan robust post-marketing strategies, and avoid promotional missteps that could trigger FDA action.

Why timing is critical

The FDA has recently updated its policies to align with scientific advancements and public health needs. The agency is now more likely to accept real-world evidence for surrogate endpoints, allowing for more flexible evaluations and clearer qualifications for what are considered acceptable endpoints, stressing the need for a strong rationale connecting them to clinical benefits.

Finally, the FDA emphasizes the need for post-marketing studies to confirm the clinical benefits of products with AA. This updated regulatory framework is meant to ensure the safety and efficacy of innovative treatments. However, the results of confirmatory trials are essential, especially within the AA pathway, as they provide the required evidence to definitively demonstrate a drug candidate’s clinical benefit.

This new guidance offers biopharma companies and drug developers a powerful pathway to transform patient care—but only if you’re ready to navigate the complexities. Start building your strategy now. Define endpoints, align CQAs, and prepare confirmatory trials to ensure your innovations don’t just reach patients faster, but stay on the market for good.

Louis Cicchini, PhD is director, scientific affairs, cell and gene therapy, and Cori Gorman, PhD is senior director, biopharmaceutical CMC and regulatory affairs; both with Cencora

Reference

1. FDA, Expedited Program for Serious Conditions — Accelerated Approval of Drugs and Biologics Guidance for Industry (December 2024). https://www.fda.gov/media/184120/download