The FDA is now operating with acting leaders in every senior position that matters for drug and biologics review. Within days of Commissioner Makary’s May 12 resignation, three additional senior leaders departed in rapid succession. Acting CDER head Tracy Beth Høeg was fired. Acting CBER head Katherine Szarama departed after serving just three weeks on the job. Chief of Staff Jim Traficant was removed from his position. Michael Davis is now acting CDER director. Karim Mikhail is acting CBER director. Lowell Zeta is acting chief of staff. Capital Alpha analysts wrote that “Makary oversaw what must be the most damaging period in FDA history” and predicted an “unprecedented” and “prolonged” leadership vacuum, adding that the administration “might struggle to find a suitable candidate who will want the job.” Drug Topics reported that CDER alone has had five different heads in a single year. BioSpace reported that fewer than half of senior FDA leaders from six months ago remain at the agency. This is not just a governance problem. It is a capacity problem that affects every NDA, BLA, advisory committee meeting, and emergency authorization—including the Ebola PHEIC response—that runs through CDER or CBER.
Top Story: FDA Leadership Cascade — Three Departures in 72 Hours
What Happened: Within days of Commissioner Makary’s resignation, three additional senior FDA leaders departed, leaving the agency with acting appointees in every critical leadership position.
The Departures
Tracy Beth Høeg (CDER acting director): Fired, according to her own social media post. Høeg had served as acting CDER head since late 2025 after Richard Pazdur departed. She rose to prominence for challenging U.S. vaccine policy during COVID-19. Reuters first reported her departure May 16. She has been replaced by Michael Davis, who had been CDER deputy director for approximately one year.
Katherine Szarama (CBER acting director): Departed after just three weeks in the role. She had replaced Vinay Prasad, who left at the end of April. Szarama is expected to remain at the FDA in another capacity to support product-related issues. Karim Mikhail, a former pharmaceutical executive who joined the FDA in 2025, has been named acting CBER director.
Jim Traficant (Chief of Staff): Removed from his position, according to The Guardian. Traficant had been chair and CEO of Citadel Sciences before joining the FDA in March 2025. He is reportedly staying on in an advisory role. Lowell Zeta, previously deputy commissioner and special counsel, was named acting chief of staff.
Five CDER Heads in One Year
Drug Topics reported that CDER—the center that oversees every small-molecule and biologic drug approval in the United States—has had five different directors in the span of a single year. That level of leadership turnover at the top of the world’s most important drug regulatory body is without precedent. Each transition requires the new acting head to learn institutional processes, build relationships with review division directors, and establish decision-making authority with career staff who have seen multiple leaders come and go.
BioSpace reported that fewer than half of senior FDA leaders from six months ago remain at the agency. The cumulative effect of this turnover extends beyond any single departure. Institutional knowledge—the understanding of how specific programs have been reviewed, what precedents have been set, and how policy commitments were made—leaves with each departing leader and takes time to rebuild.
What Capital Alpha Is Saying
Capital Alpha, a Washington policy research firm that advises institutional investors, described the situation in stark terms. The firm wrote that “Makary oversaw what must be the most damaging period in FDA history.” It predicted an “unprecedented” and “prolonged” leadership vacuum and warned that the administration “might struggle to find a suitable candidate who will want the job.”
That last point is critical. The FDA commissioner role under this administration has proven to be a position where the occupant faces pressure from political appointees (e-cigarettes, mifepristone), hostility from career staff who feel marginalized, and public criticism from industry groups, patient advocates, and congressional committees simultaneously. Makary lasted 13 months. His predecessor in spirit—a reform-minded appointee trying to balance science and politics—found the position untenable. Potential nominees are watching. The pool of qualified candidates willing to accept the role under these conditions may be smaller than the administration expects.
The Operational Impact
PharmExec described the situation as raising “near-term risks for review-cycle continuity, policy coherence, and external stakeholder confidence across drugs, biologics, and vaccines.” The practical implications are significant.
Every NDA and BLA review, every PDUFA action date, every advisory committee meeting, and every emergency authorization runs through CDER or CBER. When the people at the top of those organizations are new, acting, and potentially temporary, the decision-making process changes. Career review staff continue to do their work—the FDA’s review divisions are staffed by experienced scientists who manage day-to-day operations regardless of who sits in the director’s office. But institutional leadership sets priorities, resolves disputes between review divisions, makes final decisions on contentious applications, and represents the agency in interactions with sponsors and Congress.
Without permanent leaders, those decisions take longer, default to the most conservative option, or wait for a permanent appointee who may not arrive for months. For companies with filings pending or planned—Revolution Medicines, Lilly (Foundayo T2D), Teva (ecopipam), and dozens of others—the practical question is whether the FDA can maintain review-cycle continuity through this level of leadership disruption.
The Ebola Complication
The timing is particularly problematic because the FDA is simultaneously managing the response to the WHO’s Ebola PHEIC declaration. CBER oversees vaccine and biologic emergency responses. The new acting CBER head, Karim Mikhail, is a former pharmaceutical executive who joined the FDA in 2025—he has no institutional tenure at the agency and is now responsible for coordinating the development and potential emergency authorization of countermeasures for a Bundibugyo Ebola strain that has no approved vaccines or therapeutics.
Our Pro brief includes the full FDA leadership map showing who is in charge of what, assesses the operational impact on every filing in the queue, and analyzes what the Capital Alpha assessment means for the timeline to a permanent commissioner. [Details below.]
What to Watch
Watch for any PDUFA date changes, advisory committee postponements, or filing acknowledgment delays in the coming weeks. These would be the first tangible signs that the leadership vacuum is affecting review operations. The FDA’s organizational chart was updated on May 16 to reflect the new chain of command. Kennedy said the search for a permanent commissioner will proceed “with urgency,” but Senate confirmation (Makary was confirmed 56-44) adds further delay. Capital Alpha’s assessment that the administration may struggle to find a willing candidate suggests this vacancy could persist longer than previous commissioner transitions.
Relay Therapeutics Outpaces Novartis with 60% Response in Vascular Anomalies
What Happened: Relay Therapeutics reported data from the Phase ReInspire trial of zovegalisib in vascular anomalies, showing a 60% response rate. BioPharma Dive noted the findings “suggest the therapy could be superior to Novartis’ Vijoice at treating ‘vascular anomalies,’ a cluster of chronic conditions with few available treatments.” RLAY shares rose 11.3% in premarket trading.
Why the Data Matters
Vascular anomalies are a cluster of rare conditions involving abnormal blood vessel or lymphatic vessel growth. Novartis’s Vijoice (alpelisib) was approved in 2022 for PIK3CA-related overgrowth spectrum (PROS), but its clinical use is limited by metabolic side effects that reduce tolerability for many patients.
Zovegalisib is a PI3Kα mutant-selective inhibitor, targeting the same pathway as Vijoice but designed for improved selectivity that could translate to better tolerability. The 60% response rate in the ReInspire trial compares favorably to Vijoice’s clinical data, though cross-trial comparisons carry inherent limitations. The combination of potentially superior efficacy and improved tolerability—if confirmed in registrational studies—would give zovegalisib a compelling profile in a disease area where patients currently have few options and the existing treatment carries meaningful side-effect burdens.
If zovegalisib demonstrates a cleaner safety profile alongside superior or comparable efficacy in registrational studies, it could become the preferred treatment in a rare disease space where the current standard has significant tolerability limitations. For Relay, which has been building its precision medicine pipeline around its computational drug design platform, the vascular anomalies data is the strongest clinical validation of the company’s approach to date.
AbbVie Locks Rinvoq Generics Out Until 2037
What Happened: AbbVie reached patent settlements delaying the arrival of generic versions of Rinvoq (upadacitinib) until 2037, according to BioPharma Dive, enabling approximately four additional years of exclusivity. BioPharma Dive reported the drug generated approximately $6 billion in 2024 sales.
The Humira Playbook, Applied Again
The settlement follows the strategy AbbVie perfected with Humira, which maintained market exclusivity years beyond its original patent expiration through an extensive patent estate and settlement agreements with would-be biosimilar challengers. The approach is straightforward: build a dense network of patents covering the active molecule, formulation, manufacturing process, and methods of use. When generic or biosimilar challengers file, negotiate settlements that delay their market entry in exchange for a defined date and certainty for both parties.
For AbbVie, the Rinvoq settlement is strategically critical. The company is navigating the post-Humira transition through the combined growth of Skyrizi and Rinvoq. AbbVie raised its 2026 outlook on the strength of these two drugs and described itself as having “ample financial capacity” for M&A. Extending Rinvoq’s exclusivity to 2037 significantly reduces the near-term patent cliff risk and gives AbbVie a longer runway to build additional growth drivers through pipeline development and acquisitions—including the $1.45 billion Kestrel KRAS option deal announced in April.
For competitors developing JAK inhibitors or next-generation immunology agents, the 2037 date pushes the competitive window further out and reduces the urgency of developing Rinvoq alternatives for market share capture.
Strategic Themes
1. The FDA Is Approaching a Governance Crisis That Affects Every Company in the Industry
Five CDER heads in one year. Fewer than half of senior leaders remaining from six months ago. Acting appointees in every critical position. The scale of leadership disruption at the FDA is without modern precedent. Capital Alpha’s characterization—”the most damaging period in FDA history”—reflects the view from Washington policy analysts who advise institutional investors. For pharmaceutical companies, the risk is not that the FDA stops working entirely. Career staff continue processing applications. The risk is that the pace slows, that contentious decisions get deferred, and that the regulatory predictability the industry depends on erodes incrementally as each acting leader brings a shorter time horizon and less institutional authority than a permanent appointee would.
2. Relay’s 60% Response Rate Positions Zovegalisib as a Potential Best-in-Class in Vascular Anomalies
Novartis’s Vijoice established the PI3Kα pathway in vascular anomalies but is limited by tolerability. Relay’s mutant-selective approach could address that limitation while delivering comparable or superior efficacy. The 60% response rate and the 11.3% stock move signal that the market views the data as commercially meaningful. If registrational data confirm the Phase findings, zovegalisib could displace Vijoice as the standard of care in a rare disease market with limited competition and high unmet need.
3. AbbVie’s Rinvoq Settlement Shows Patent Strategy Remains the Most Valuable Competitive Tool in Pharma
Four additional years of exclusivity on a $6 billion drug. The Rinvoq settlement demonstrates that patent strategy—building, defending, and settling around an extensive IP estate—remains one of the most financially valuable activities any pharmaceutical company can execute. AbbVie proved the model with Humira. It is now proving it again with Rinvoq. For every company managing a patent cliff, the AbbVie playbook is the template for maximizing the revenue runway of a blockbuster franchise.
4. ASCO Is 10 Days Away and the Regulatory Environment Has Never Been More Uncertain
Revolution Medicines’ plenary presentation on May 31 will produce the most anticipated oncology data of the year. Truist has projected a Q3 approval if Revolution files under CNPV. But the CNPV program’s creator is gone, the CDER director is an acting appointee with one year of FDA tenure, and the CBER director has been on the job for days. The collision of transformative clinical data with an FDA in institutional disarray creates a unique moment of both opportunity and uncertainty for the oncology pipeline.
Frequently Asked Questions
Who is now running the FDA?
Acting Commissioner Kyle Diamantas (food background). Acting CDER Director Michael Davis (CDER deputy director for approximately one year). Acting CBER Director Karim Mikhail (former pharmaceutical executive, joined FDA 2025). Acting Chief of Staff Lowell Zeta (deputy commissioner/special counsel). All are acting appointees. No permanent nominees have been announced.
How many CDER heads has the FDA had in one year?
Five, according to Drug Topics. The turnover at the top of CDER—the center responsible for every drug approval in the United States—is unprecedented.
What did Capital Alpha say?
The policy research firm wrote that “Makary oversaw what must be the most damaging period in FDA history,” predicted an “unprecedented” and “prolonged” leadership vacuum, and warned the administration “might struggle to find a suitable candidate who will want the job.”
Does the leadership vacuum affect pending drug applications?
There is no current indication that PDUFA timelines have slipped. Career FDA review staff continue managing day-to-day operations. But institutional leadership sets priorities, resolves disputes, and makes final decisions on contentious applications. Without permanent leaders, decisions may take longer or default to more conservative outcomes. PharmExec described “near-term risks for review-cycle continuity.”
What is the Relay Therapeutics data?
Zovegalisib showed a 60% response rate in vascular anomalies in the Phase ReInspire trial. BioPharma Dive said the data “suggest the therapy could be superior to Novartis’ Vijoice.” Zovegalisib is a PI3Kα mutant-selective inhibitor designed for improved tolerability versus Vijoice. RLAY shares rose 11.3%.
What is the AbbVie Rinvoq settlement?
Patent settlements delaying generic Rinvoq until 2037, approximately four additional years of exclusivity. The drug generated roughly $6 billion in 2024 sales. The settlement follows AbbVie’s Humira playbook of building dense patent estates and negotiating delayed generic entry.
What about the BioMarin Phase 3 failure?
BioMarin reported a Phase 3 failure in its rare disease portfolio. BioSpace described it as “another blow” for the company, which has faced multiple pipeline setbacks. Specific program details and indication were not immediately available in initial reports. The company’s rare disease franchise is built around Voxzogo (achondroplasia, growing rapidly) and Roctavian (hemophilia A gene therapy, which has faced commercial challenges since launch). A Phase 3 miss in an additional rare disease program narrows the pipeline diversification that BioMarin needs to sustain its growth trajectory beyond its two anchor products.
When is ASCO?
May 29 through June 2 in Chicago. Revolution Medicines plenary session May 31. Full Phase 3 RASolute 302 data. The conference is 10 days away.
BioMed Nexus Pro — What Institutional Subscribers Are Reading Today
FDA Governance Crisis: The Full Map. We compile the complete FDA leadership chart showing who is running every critical center and office, assess the operational impact on filings in the queue, and analyze what Capital Alpha’s “might struggle to find a candidate” assessment means for the timeline to a permanent commissioner and the institutional stability of the agency.
Relay vs. Novartis in Vascular Anomalies. We analyze why PI3Kα mutant selectivity could differentiate zovegalisib from Vijoice, assess the commercial opportunity in a rare disease market with limited competition, and model what a registrational pathway would look like for Relay.
AbbVie’s Patent Playbook. We break down how the Rinvoq 2037 settlement mirrors the Humira IP strategy, model the cumulative revenue protected by four additional years of exclusivity, and assess what the settlement means for AbbVie’s post-cliff transition alongside Skyrizi growth and M&A capacity.
Plus: BioMarin Phase 3 failure assessment, Ebola PHEIC response under new CBER leadership, ASCO 10-day countdown, and the updated catalyst calendar through H2 2026.
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