407: The mysterious case of Eli Lilly's obesity drug

The episode opens with hosts Allison DeAngelis and Elaine Chen discussing the biotech industry's bustling news cycle despite political uncertainty in Washington. They report that 33 acquisitions valued over $1 billion have occurred in the past six months—exceeding last year's total—with pharmaceutical and biotech companies spending approximately $134 billion on M&A as they prepare for patent cliffs and revenue challenges. Eli Lilly emerges as the largest M&A player, though companies like Biogen, UCB, and Insight are also making significant acquisitions, indicating diverse dealmaking activity. The returning IPO market for biotechs is also affecting acquisition premiums, as companies now have more financing alternatives beyond M&A.

The conversation then shifts to Eli Lilly's investment in Upside Therapeutics, a hair loss drug developer that raised $100 million led by Lilly. Hosts note the apparent contradiction between framing obesity as a serious chronic disease while simultaneously moving into aesthetics-focused products and direct-to-consumer marketing. They discuss how GLP-1 drugs cause hair loss as a side effect and how patients on weight loss drugs may scrutinize their appearance more closely, creating a natural market fit for aesthetic treatments.

Regenexx Bio's FDA interactions are examined next, showing that the agency has reversed restrictive stances on gene therapies for Hunter syndrome and Duchenne muscular dystrophy that were previously required under former leadership. The hosts note this mirrors similar reversals in the Unicure case from the previous week, suggesting systemic changes in FDA philosophy.

FDA reporter Lizzie Lawrence joins to discuss the centerpiece story: Eli Lilly's compassionate use program for retatrutide (the triple-G obesity drug targeting GLP-1, GIP, and glucagon), which has been granted to exactly one 79-year-old overweight man with pulmonary hypertension. Lawrence explains that she investigated whether this was President Trump due to: demographic alignment, his previous COVID compassionate use access, and unusual high-level FDA involvement in what is typically a routine process. The White House initially demurred but eventually denied the patient was Trump. Lawrence and the hosts discuss the ethical implications: obesity affects 40 million Americans, and other physicians attempting to secure compassionate use for their unresponsive patients were not granted access. The sparse posting of the program on clinicaltrials.gov with minimal qualifying information raises fairness concerns. Experts emphasize that compassionate use policies should apply uniformly regardless of a patient's prominence.

The discussion moves to FDA efforts to streamline clinical trials, which the agency announced through Acting Commissioner Diamantis and CBER director Kareem Mikhail. Proposed changes include reducing the default requirement from two pivotal trials to one and releasing guidance on dose selection. However, Lawrence notes these changes remain vague and somewhat performative, and the real structural advantages for clinical trials exist in China through integrated hospital systems and pre-authorized manufacturing infrastructure. She observes that statutory authorities may require Congressional clarification before the FDA can implement more significant flexibility.

Lawrence provides insight into the FDA's recent reversals of high-profile gene therapy decisions, attributing them to new leadership's focus on undoing restrictive decisions from the Prasad era and moving toward greater flexibility aligned with right-to-try principles from the first Trump administration. Potential FDA commissioner candidates mentioned include Heidi Overton (White House Policy Council), Ned Sharpless (former acting FDA commissioner and NCI director), though timing for announcement remains uncertain.

When asked about the morale and dynamics of an acting commissioner leading major policy changes, Lawrence notes relief that political leaders seem less interested in meddling with career staff decisions, though she flags potential flashpoints ahead: peptide regulation (where FDA staff oppose unleashing untested peptides despite Secretary Kennedy's stance) and mifepristone access (facing pressure from anti-abortion advocates to restrict mail and telehealth prescribing).

The episode concludes with a sponsored segment featuring Dr. Mika Kakafuda-Durink and Dr. Galia Levy from Gilead Sciences and Kite (a Gilead subsidiary) discussing their oncology strategy centered on antibody-drug conjugates and CAR-T cell therapies. They highlight that Kite has treated over 34,500 patients with CAR-T therapies—more than any competitor—while only about 2 of 10 eligible patients currently access CAR-T. They discuss expanding treatment centers (currently 600 worldwide), improving manufacturing reliability (96% success rate), and exploring applications beyond blood cancers into solid tumors like glioblastoma.