CBER’s Prasad Outlines Rare Disease Goals
CBER director Vinay Prasad is embracing both surrogate endpoints for accelerated approval and overall survival data in confirmatory studies for rare disease products. Speaking at the 6/3 National Organization for Rare Disorders’ (NORD) Rare Disease Scientific Symposium, Prasad reassured companies, researchers and patients that FDA “will take action at the first sign of promise for rare diseases. We’re not going to wait to learn about the 30-year consequences of a therapy. We don't have time to wait. We’re going to take action at the earliest statistically persuasive biomarker changes that are reasonably likely to predict clinical outcomes per the accelerated approval pathway.”
Prasad said that it’s also important for firms to establish a benefit in overall survival and that people are living longer and better lives. “So that’s going to be holding companies more accountable for post-marketing requirements and post-marketing commitments,” he told NORD. “When you make a post-marketing commitment, we're going to want those post-marketing commitments fulfilled.”
Regarding real-world data, Prasad said this will prominently be used at CBER with rare diseases. “We’ll use real-world data to draw inferences about whom these drugs are being given,” he said. “We’ll use real-world data to identify safety signals that cannot be identified in studies of 100 or 200 people or even 10 people. “We will use real-world data in every way possible to draw more conclusions about what these products are accomplishing.” He also said CBER will recommend target trial emulation, propensity score match studies, and inverse probability weighted studies in instances where it is impossible to conduct traditional randomized controlled trials. “FDA will also be flexible and permissive in letting products to the U.S. market, particularly for rare diseases that are dire… and have no acceptable treatment options.”
Prasad said FDA and CBER are looking to improve their engagement with stakeholders to ensure better therapies come to market. There will be more open discussions about regulatory topics through Youtube videos and a new FDA commissioner podcast called FDA Direct, he said. CBER will also continue to publish in the peer-reviewed literature. For example, a JAMA (XXX ITALICS XXX)paper is coming out on 6/5 about a “particular vaccine that has a safety pause on it because of an adverse safety signal that's quite concerning to us at FDA,” he said. “We have another paper coming where Dr. Makary is going to lay out his philosophy at FDA, also in JAMA.”
Prasad said FDA will host round tables and there is one scheduled for 6/5 about cell and gene therapies. “And we have a CEO listening tour where Dr. MaKary and I are going to go city to city, and we’re going to hear from CEOs from big and small companies to know what their experience has been with FDA,” he told NORD, adding that “FDA will no longer be opaque. It’s not going to be an FDA where you don't understand what we're thinking, we’re going to tell you what we’re thinking as clearly and as simply as we can without losing the core message.”
In response to a question about product review interference, Prasad said he plans to keep his distance as the organization chart dictates. “The primary study teams do the reviews, and they have people who oversee them, and gradually things filter up to the Center director,” he said. “So as a general rule, the Center director is not the primary study reviewer, and making those primary study formulations. At the same time, I’m interested in learning about those things and what people are thinking, and hearing from those groups. And so far, I’ve asked a couple of those groups to present to me what they’re working on. But my understanding is that’s the way it’s always been among the Center directors. So I think we’ll continue to do that.”