FDA is preparing a major reform in the approval of rare disease drugs! Patients' right to speak out is enhanced, and the path for pharmaceutical companies to be regulated is expected to be clearer

The Zhitong Finance App learned that the US Food and Drug Administration (FDA) is initiating a comprehensive top-down review to re-evaluate how it operates in rare disease drug development and approval. The FDA will announce the “Rare Disease Framework Initiative” on Wednesday. The initiative aims to establish a new system that allows patients to have more say in the regulatory process while providing a more clear regulatory path for pharmaceutical companies.

The move comes at a time of turbulence for the FDA. During the tenure of former FDA Director Marty Macari, several rare disease drugs were unexpectedly rejected or approval postponed. Makari left the FDA in May. The related incident triggered a congressional investigation. Pharmaceutical companies filed a complaint with the White House, and patient groups also expressed opposition to this.

In an interview, a senior FDA official denied that the initiative was linked to previous controversy. They said this is an FDA effort to continuously improve the rare disease drug development process, and as the proportion of rare disease drugs in FDA-approved drugs continues to increase, this work is even more important.

Karim Mikhail, head of the FDA's Center for Biologics Evaluation and Research, which oversees cell and gene therapies, said, “This is a real move aimed at changing the way we review drugs for rare diseases.”

According to reports, the new framework aims to enable patients to provide opinions at an earlier stage and at various key points throughout the drug development and review process. At the same time, the framework also hopes to provide drug developers with greater clarity and consistency in regulatory decisions. The FDA said in a statement that the framework should take into account the specific nature of rare diseases and what evidence can reasonably be obtained in such circumstances.

Currently, patients usually only express opinions through the advisory committee after the drug has entered the approval stage, clinical trials have been completed, and FDA reviewers have basically completed their work. At the same time, pharmaceutical companies may also invest significant resources in drug testing, but ultimately disagree with regulators over what data the FDA requires to obtain approval.

Amy Comstock Rick, FDA's Deputy Director of Rare Disease Strategy, said FDA officials should “always clearly state requirements to drug developers” throughout the process. “There should be no accident,” she added.

According to FDA data, about 30 million people in the US suffer from rare diseases. As of 2025, of the 70 to 10,000 rare diseases that have been identified, only about 5% have treatments approved by the FDA. The new initiative will officially launch on October 28 at a conference to hear from patient groups, disease advocacy organizations, industry, and other stakeholders.

The scope of this action goes far beyond an early initiative launched during Makari's tenure — the so-called “reasonable mechanism” approval path. The initiative focuses on the rarest diseases, those with only a single digit number of patients.

Michael Davis, director of the FDA's Center for Drug Evaluation and Research, said that the new framework will not adopt a top-down approach, but rather hopes to include the opinions of ordinary FDA staff. “We really want to advance this initiative in the right way,” he said.

FDA officials said in an interview that the initiative could eventually result in formal guidance documents or regulatory regulations. Judging from internal targets, the FDA hopes to make initial recommendations by February next year, but this schedule may be adjusted based on feedback received.

Since Makari left office, the FDA has not had an official long-term director. White House policy adviser Heidi Overton was nominated to lead the FDA, and her nomination is still awaiting review by the Senate. Last month, Karim Mikhail and Michael Davis were officially announced as heads of their respective supervisory centers.