FDA’s ARC Program Highlights Opportunities and Limits of Bayesian Methods in Rare Disease Trials

Bayesian methods may offer opportunities to develop clinical endpoints for rare diseases, but small patient populations can limit how quickly evidence accumulates. Paz Vellanki, MD, PhD, vice president of clinical development at Precision for Medicine, discussed both the potential and the limitations of these approaches in this second part of a two-part video interview with BioPharm International.

“It's definitely an important opportunity to develop endpoints in rare diseases, but there are still some barriers given again that you have smaller populations of patients that you're accumulating data from,” Vellanki said.

How can sponsors build a stronger path toward approval?

Bayesian methods can incorporate accumulating data to inform endpoint development. However, in rare diseases, limited patient numbers may constrain the amount of evidence available to refine and evaluate new endpoints over time.

Vellanki cautioned that these approaches do not eliminate the challenges associated with small study populations. Instead, she sees them as part of a broader effort to explore innovative ways to generate evidence for diseases where established clinical endpoints may be lacking.

Bayesian methods may offer one way to use accumulating data to inform endpoint development in rare diseases. However, small patient populations can limit how quickly sponsors generate enough evidence to support these approaches. FDA has also discussed innovative trial designs for rare disease cell and gene therapies, including Bayesian methods and externally controlled studies. Read more about FDA’s guidance on innovative trial design for rare-disease CGTs.

The FDA’s Center for Drug Evaluation and Research (CDER) is reinforcing this effort through its Accelerating Rare disease Cures (ARC) program. Its five-year roadmap builds on earlier initiatives and pilot programs designed to create more opportunities for sponsors to engage with regulators.

For Vellanki, one of the biggest mistakes sponsors can make is advancing a clinical development program without discussing their overall strategy with FDA, particularly when working in complex disease areas or developing novel endpoints.

An early-phase protocol that FDA considers safe to proceed does not necessarily establish that a study will generate the evidence needed to support approval.

Sponsors should therefore consider their intended regulatory outcome from the beginning and seek FDA input on trial design, endpoints, and the evidence needed to support a future application.

“The biggest misstep I was seeing is that the sponsors aren't reaching out to FDA,” Vellanki said.

Her advice is to engage early, particularly when development plans rely on innovative methods or endpoints that have not yet been well established.

View part one of this interview here.

About the Speaker

Paz Vellanki, MD, PhD, vice president of clinical development, oncology, Precision for Medicine

Paz Vellanki partners with life sciences companies on clinical development strategy and regulatory planning. Before joining Precision for Medicine, she served as associate director of the Division of Oncology 2 at the FDA where she oversaw drug development and regulatory decisions for therapeutics in lung cancer, head and neck cancer and rare tumors and molecular subsets of cancers.