New FDA Commissioner Takes Office and Fires the First Shot!

Since the end of last year's U.S. presidential election, the country’s public health and healthcare sector has gone through months of turmoil.

At the FDA, news of resignations began surfacing during the election. As of January 2025, according to incomplete statistics, several senior officials had announced their retirement or resignation: Dr. Namandjé Bumpus (Deputy Commissioner), Dr. Doug Throckmorton (Deputy Director of Regulatory Programs), and Dr. Robert Temple, who had served at CDER for 52 years. By the end of March, as a wave of FDA layoffs sparked heated debate, renowned FDA official Dr. Peter Marks, Director of CBER, also announced his resignation.

These personnel changes in key positions, along with the unusually large-scale layoffs, have pushed the FDA into a state of dysfunction, leading to review delays and other crises.

Now, with both the new Secretary of Health and Human Services (HHS) and the new FDA Commissioner officially in place, true reform appears to be underway. Whether the new FDA leader can balance competing demands and restore the agency's functionality will be a key focus in the months ahead.

New Commissioner Targets Rare Diseases

On April 1, 2025, Martin A. Makary was sworn in as the 27th Commissioner of the FDA. His nomination, proposed by former President Trump, was approved by the Senate with a vote of 56 in favor and 44 against.

Makary holds a Master of Public Health from Harvard University and is a member of the National Academy of Medicine. Before taking on his FDA role, he was a surgeon at Johns Hopkins University, specializing in oncology and advanced laparoscopic surgery. He also served as a professor of health policy and management at the Bloomberg School of Public Health. Makary is also a published author, having written New York Times bestsellers and contributing regularly to The Wall Street Journal, The New York Times, and USA Today, in addition to serving as a frequent medical commentator.

In his inauguration announcement, Makary said:

How can we advance our mission? Fulfill our promises? Make America healthy again? His upcoming reform measures have stirred considerable anticipation.

Just last Friday, in an interview with SiriusXM host Megyn Kelly, Makary revealed that the FDA might reform the approval process for certain rare disease drugs. This includes creating a new customized conditional approval pathway for treatments targeting extremely rare diseases. Makary stated, "We will introduce new drug approval pathways based on a reasonable mechanism of action." He clarified that such approvals would be "conditional" and would not require randomized controlled trials (RCTs).

What does this mean? Without the need for RCTs, approval timelines could be drastically shortened, allowing patients quicker access to life-saving treatments. Smaller biotech firms might also be more inclined to enter the rare disease field, given the lower financial barriers.

However, this approach has downsides: without RCT data, a drug’s actual effectiveness may fall short of expectations, or pose unknown safety risks. In response to such concerns, Makary said the FDA will conduct strict monitoring of patients using these drugs until clearer data signals emerge.

More Reforms on the Way

Driven by policy support, rare disease drug development is flourishing in both China and the U.S. According to the FDA, 481 drugs were granted Orphan Drug Designation (ODD) in 2024. This represents significant growth compared to just over a decade ago—back in 2011, the number of ODD approvals first exceeded 200.

Makary’s idea of waiving RCTs for some rare disease treatments partially draws on Dr. Peter Marks’ earlier work on accelerating gene therapy approvals, as well as legislation proposed by then-Senators Mike Braun (R-IN) and Kirsten Gillibrand (D-NY). These policies aim to establish mechanisms for granting time-limited conditional approvals to rare disease drugs with solid early safety and efficacy data. Makary explained, "Suppose a disease only affects 75 patients globally, and the new therapy is physiologically sound—its mechanism of action scientifically suggests effectiveness."

During the interview, Makary also described the FDA’s internal structure as "severely fragmented," stressing the need for better team collaboration. Previous media reports outlined early reform plans to consolidate certain functions into five "shared services" offices. Makary also emphasized the need to leverage technology to better track adverse drug events, calling for a "high-quality adverse event tracking system." The FDA will more frequently use electronic health records to verify real-world complication rates and improve post-market evaluations.

"When post-market surveillance fails, problems might only emerge a decade later," Makary warned. "If we do a better job monitoring drugs and devices after approval, we can ask companies: Why not do one randomized trial instead of two? This is especially important in the field of rare diseases."