In his first major interview since taking office just over two weeks ago, FDA Commissioner Marty Makary revealed plans for a new regulatory pathway designed specifically for rare disease treatments, potentially allowing drug approvals without traditional randomized controlled trials.
Speaking on The Megyn Kelly Show on Friday, Makary outlined a "plausible mechanism" approach that would focus on rare or incurable diseases affecting small patient populations where conventional clinical trials may not be feasible.
"If there is an investigational drug that makes sense physiologically—the mechanism is scientifically plausible that this treatment would help these individuals—we could approve that therapy on a conditional basis," Makary explained.
The Proposed Rare Disease Pathway
The new pathway would represent a significant shift in the FDA's approach to evaluating treatments for rare diseases, which often face unique challenges in the traditional approval process due to small patient populations and difficulty recruiting for clinical trials.
Key elements of the proposed pathway include:
- Conditional approvals based on scientific plausibility rather than extensive clinical trial data
- Focus on diseases affecting "a small number of people" with limited treatment options
- Implementation of a comprehensive patient surveillance system to monitor outcomes
- Real-time data collection to enable rapid assessment of safety and efficacy
"We would monitor everybody who gets [the treatment], so that we can make inferences as soon as the data speaks," Makary said, emphasizing that "no one is forcing these medications [on patients]."
This initiative appears to build on the regulatory flexibility championed by Peter Marks, the former head of the Center for Biologics Evaluation and Research, who departed the agency late last month. In a July 2024 interview, Marks had stressed the importance of accelerated approvals for rare disease therapies, noting that timely treatment could dramatically improve patients' quality of life.
Addressing Public Trust Concerns
During the interview, Makary also acknowledged what he described as an "epidemic of distrust" toward the FDA and other U.S. health authorities. He suggested that "part of it is warranted," particularly regarding how adverse events have been monitored and reported.
Makary criticized the current Vaccine Adverse Event Reporting System (VAERS), which relies on self-reported data from patients and physicians. "You can make no inferences about rates using self-reported data," he stated. "That's just a basic scientific methodological principle."
To address these limitations, Makary announced plans to implement a more comprehensive monitoring system using what he called the "Health Information Exchange," which he described as a "massive" repository of electronic health record data. This approach would allow the FDA to analyze real-world complication data more effectively.
Implications for Rare Disease Communities
For the estimated 30 million Americans living with rare diseases—many of which have no FDA-approved treatments—this proposed pathway could represent a significant development. Rare disease advocacy groups have long pushed for more flexible regulatory approaches that acknowledge the unique challenges of developing therapies for small patient populations.
The proposal comes at a time when the FDA has been under scrutiny for its approval standards, with some critics arguing for more stringent requirements while others advocate for greater flexibility, particularly for conditions with high unmet medical needs.
Industry experts note that the success of such a pathway would depend heavily on the specific criteria used to evaluate "plausible mechanisms" and the robustness of the post-approval monitoring systems. The balance between providing earlier access to potentially beneficial treatments and ensuring adequate safety protections will likely be a central consideration as the FDA develops this initiative further.
Makary's announcement signals a potentially significant shift in regulatory philosophy early in his tenure as commissioner, suggesting that rare disease drug development may become a priority focus under his leadership.
