401: Makary’s departure and Cassidy’s tenuous Senate seat

The episode opens with a brief recap of listener milestone celebrations for episode 400, then transitions into science news. Adam Feuerstein discusses Biogen's mid-stage trial results for a tau-targeting RNA-based drug (BIB080) for Alzheimer's disease, noting that while the study technically failed its primary endpoint (lowest dose performed best with no clear dose response), Biogen is moving forward to Phase 3. He cautions that Biogen's use of positive adjectives in its press release may be a red flag, and that actual data won't be presented until a London Alzheimer's conference in July.

The hosts then cover Regenix Bio's gene therapy (RGX-202) for Duchenne muscular dystrophy, which showed strong microdystrophin levels. Despite positive efficacy and safety data, the company has delayed its FDA application from late 2025 to early 2027 due to regulatory uncertainty — including leadership turmoil at both the FDA commissioner level and within CBER following Vinay Prasad's departure.

The bulk of the episode focuses on Washington DC health policy. DC correspondent Lizzie Lawrence explains Makary's departure, describing it as the result of accumulated political grievances: the vaping community was angry at his slow approval of flavored vapes, the pro-life community was frustrated by his alleged slow-rolling of a mifepristone safety study, rare disease advocates were upset over restrictive decisions, and there were organizational challenges including staff departures and unpredictable decisions. The Journal reported Trump was particularly angry about the vaping issue. While Makary had 'nine lives' given months of departure rumors, the combination of factors ultimately led to his exit.

Acting commissioner Kyle Diamantis is described as a corporate attorney with no medical or scientific background, previously a Jones Day partner who represented food and beverage companies. Industry sources describe him as someone who 'radiates normal,' thinks constructively about problem-solving, and respects career staff — a contrast to Makary's high-profile, often chaotic approach. Concerns remain about his ability to resist political pressure given his close alignment with Trump. Lizzie notes that among Makary's initiatives, those most likely to endure include the animal testing reduction guidance, the plausible mechanism framework for rare diseases, streamlining clinical trials, and releasing Complete Response Letters.

Chelsea Ceruzzo reports on Senator Bill Cassidy's vulnerability in the Louisiana Republican Senate primary, stemming from his vote to convict Trump during impeachment proceedings and his ultimately controversial vote to confirm RFK Jr. as HHS Secretary despite Kennedy's anti-vaccine history. Cassidy, a physician who personally vaccinated children in Louisiana and consulted with vaccine co-inventor Paul Offit before the Kennedy vote, was unable to satisfy either moderate or hard-right voters. The newly closed Republican primary format disadvantages Cassidy, who previously relied on moderate and independent voters. Trump has endorsed challenger Julia Letlow. Chelsea argues that Cassidy's loss would remove a key congressional check on Trump's health care agenda, as his committee has oversight over HHS nominees including the next FDA commissioner, CDC director, and Surgeon General.