It’s over. FDA Commissioner Marty Makary resigned on Tuesday after 13 months in the role. The resignation followed days of reporting that the White House had signed off on a plan to replace him. The final trigger was a disagreement over flavored e-cigarette authorization, which Makary opposed but was overruled on. A source told CNN that Makary “doesn’t want to approve youth-appealing flavors, but has been forced to by the powers that be.” The New York Times reported that this conflict was “what ultimately prompted Makary’s decision to resign.” Kyle Diamantas, deputy commissioner for food, has been named acting commissioner. Three Senate-confirmed health positions are now vacant: FDA commissioner, CDC director, and surgeon general. HHS Secretary Robert F. Kennedy Jr. praised Makary on social media and said “the search for a new Commissioner is already underway, and we will move forward with urgency.” The practical impact on pharma is immediate: PDUFA reauthorization negotiations are underway, the CNPV program has active filings, the Expedited IND pathway needs a champion, and the RTCT pilot is supposed to launch this summer. The industry’s chief regulator is gone. And the three most important Senate-confirmed health positions in the country are sitting empty.
Top Story: Makary Resigns After 13 Months — Diamantas Named Acting Commissioner
What Happened: FDA Commissioner Marty Makary resigned on Tuesday May 12, ending a turbulent 13-month tenure. The Washington Post reported the resignation came “after months of turmoil at the agency and White House staff last week signing off on a plan to replace him.” Trump announced Kyle Diamantas as acting commissioner on Truth Social. Diamantas was elevated to be one of Kennedy’s deputy secretaries and oversees the FDA’s food program.
The Final Trigger Was E-Cigarettes, Not Drugs
Multiple outlets reported that the immediate cause was Makary’s opposition to authorizing fruit-flavored e-cigarettes. Trump had pledged to protect the vaping industry during the 2024 campaign. The FDA announced its first approval of fruit-flavored vapes shortly before Makary’s departure. Harvard’s Dr. Aaron Kesselheim told Democracy Now: “Nobody was happy with what he did.”
CNBC reported that a senior administration official “couldn’t point to one issue” but described “a buildup of many problems,” including abortion policy. The mifepristone handling angered anti-abortion groups. Former cancer regulator Dr. Richard Pazdur cited Makary’s leadership as his reason for leaving the agency. Multiple senior scientists departed during his tenure. Staff morale had “plummeted after layoffs and departures of career agency scientists,” per CNBC. Axios noted that Makary’s departure means three Senate-confirmed health positions are now vacant: FDA commissioner, CDC director, and surgeon general.
Makary Tried to Hold the Center — Neither Side Was Satisfied
Makary’s 13-month tenure was defined by an attempt to balance the MAHA agenda with traditional FDA regulation. He approved Foundayo in 50 days under the CNPV program—a genuine acceleration of drug review that the industry welcomed. He launched the Expedited IND pathway, the Real-Time Clinical Trial initiative, and psychedelic therapy fast-tracks. He maintained a high evidentiary bar for single-arm oncology studies with the RP1 second CRL. He oversaw three new molecular entity approvals under the CNPV (Foundayo, Otarmeni, Bizengri).
But he also presided over an agency that lost senior career scientists, operated with acting directors in both CDER divisions, and faced political pressure on issues (e-cigarettes, mifepristone, dietary supplements) that had nothing to do with drug development. Kesselheim’s summary—”nobody was happy with what he did”—captures the impossibility of the position he occupied. The pharmaceutical industry valued his drug development initiatives. The political apparatus valued compliance with its priorities. The two were irreconcilable.
What Diamantas Means for Drug Development
Kyle Diamantas comes from the food side of the FDA. He has no known track record on drug development policy. His appointment as acting commissioner creates a leadership situation where the person overseeing the world’s most important drug regulatory agency has spent their career focused on food safety.
This does not necessarily mean drug development programs will stall. The FDA has deep institutional expertise in its drug review divisions, and career staff can continue processing applications without commissioner-level intervention on individual decisions. Standard NDA and BLA reviews are driven by review division timelines and PDUFA performance goals, not by commissioner direction.
But commissioner-level programs are different. The CNPV is a commissioner-driven initiative that was created under Makary’s direction and requires active championship to maintain its pace. The Expedited IND is a legislative proposal that needs a commissioner to advocate for it in Congress during PDUFA reauthorization negotiations. The RTCT pilot requires leadership direction to expand from proof-of-concept to a formal program. These are not programs that operate on autopilot. They require active championship from the commissioner’s office to maintain momentum, allocate resources, and protect against bureaucratic resistance.
The PDUFA reauthorization adds another dimension of urgency. The Prescription Drug User Fee Act expires September 30, 2027. Negotiations between the FDA and industry are already underway. PDUFA sets the fee structures, review timelines, and performance goals that govern every NDA and BLA submission. These negotiations are complex, multi-stakeholder processes that benefit from stable FDA leadership. Conducting them during a leadership vacuum—with an acting commissioner from the food side of the agency—introduces uncertainty into one of the most consequential regulatory processes the industry faces.
The Three Vacant Positions
Axios reported that Makary’s departure means three Senate-confirmed health positions are now vacant simultaneously: FDA commissioner, CDC director, and surgeon general. The leadership vacuum extends beyond the FDA itself to the broader federal health infrastructure. For an administration that has publicly prioritized health reform under the MAHA agenda, the absence of confirmed leaders at the three most prominent health agencies is a notable gap between rhetoric and institutional capacity.
The Search Is Underway
Kennedy said the search for a permanent commissioner “is already underway” and that the administration “will move forward with urgency.” Makary was confirmed 56-44 by the Senate, reflecting the partisan dynamics that any nominee will face. Stephen Hahn (FDA commissioner 2019 to 2021) and Brett Giroir (former acting commissioner and HHS assistant secretary) have been discussed as potential nominees.
A permanent nominee requires Senate confirmation, which typically takes months from nomination through committee hearings and floor vote. Makary’s own confirmation took several weeks and passed 56-44, reflecting the partisan dynamics that any nominee will face. During the interval between Makary’s departure and a confirmed successor, Diamantas holds the acting role. The longer the gap, the more regulatory momentum dissipates on commissioner-driven initiatives—and the more the industry operates in an environment where the person running the FDA has no mandate to make long-term policy decisions.
Our Pro brief includes the updated risk assessment for every regulatory initiative Makary championed—CNPV, Expedited IND, RTCT, PDUFA reauthorization, and FDA staffing—with risk levels adjusted for the confirmed departure. [Details below.]
European Mid-Caps Are Buying American Biotechs at an Accelerating Pace
What Happened: BioSpace reported on Tuesday that mid-sized European drugmakers are “snapping up US biotechs” at an accelerating pace, with differing views on whether the activity represents “the rise of a new buyer class or a quirk of timing.”
The Deal List
Recent acquisitions by European mid-cap companies tell a consistent story:
Chiesi (Italy): KalVista for $1.9 billion (hereditary angioedema, April 29). Angelini (Italy): Catalyst Pharmaceuticals for $31.50 per share (neurology, May 8). UCB (Belgium): Candid Therapeutics for $2.2 billion (autoimmune TCE, May 12) plus Neurona Therapeutics for $1.15 billion (epilepsy cell therapy, April 17). LEO Pharma (Denmark): Replay gene therapy (rare dermatology, May).
Combined, European mid-cap acquirers have deployed more than $5.5 billion in announced deals in the past month.
Why This Is a Structural Shift
Historically, cross-border biopharma M&A has been dominated by European mega-caps—Novartis, Roche, AstraZeneca, Sanofi. The emergence of Chiesi, Angelini, UCB, and LEO as active acquirers signals that the M&A wave has broadened beyond the usual suspects.
The drivers are the same as their U.S. counterparts: patent cliff pressure, pipeline gaps, and attractive biotech valuations that remain below 2021 highs. But European mid-caps bring a distinctive pattern: each company is acquiring U.S. biotechs to extend established commercial franchises in specific therapeutic areas. UCB (immunology/neuroscience) bought Candid (autoimmune) and Neurona (epilepsy). Chiesi (rare disease) bought KalVista (HAE). Angelini (neurology) bought Catalyst (Lambert-Eaton). LEO (dermatology) bought Replay (gene therapy for genetic skin disease).
The consistency of this strategic logic across four different companies, four different countries, and four different therapeutic areas suggests a structural pattern rather than coincidence. For clinical-stage U.S. biotechs, European mid-caps represent a buyer class that did not meaningfully exist 18 months ago.
Our Pro brief analyzes why the European buyer wave is structural rather than coincidental and which therapeutic areas are most likely to attract additional European mid-cap acquisitions in H2 2026. [Details below.]
New Cardiovascular Guidelines Push for More Aggressive LDL Reduction
New cardiovascular guidelines from the American Heart Association and American College of Cardiology call for more aggressive management of LDL cholesterol, emphasizing sustained low levels of apolipoprotein B and LDL particles as key targets. BioSpace reported that Merck and Amgen are “doubling down” on the opportunity.
Why This Matters for Pharma
Updated treatment guidelines directly affect prescribing behavior and, by extension, the commercial opportunity for the drugs they recommend. If the new AHA/ACC guidelines move PCSK9 inhibitors and next-generation lipid-lowering agents from specialty prescribing (reserved for the highest-risk patients who fail statins) to broader primary care use (recommended for a wider population that does not achieve adequate control on statins alone), the addressable market expands significantly.
Amgen’s Repatha and other established PCSK9 inhibitors are positioned to benefit immediately. Merck is advancing its own PCSK9 program. Next-generation lipid-lowering agents also gain relevance under guidelines that emphasize sustained low LDL and apoB levels.
The cardiovascular drug market has been relatively quiet compared to oncology and GLP-1 in recent years. These guidelines, combined with active pipeline investment from multiple large pharma companies, could mark the beginning of a cardiovascular growth cycle that has been absent from the industry narrative.
BridgeBio’s Attruby Shows Survival Signal vs. Pfizer’s Tafamidis
BioSpace separately reported that indirect comparisons between BridgeBio’s Attruby and Pfizer’s tafamidis products showed a numerical survival benefit with BridgeBio’s drug in transthyretin amyloid cardiomyopathy (ATTR-CM). While indirect comparisons carry significant limitations that make definitive conclusions premature, the data position Attruby as a potentially differentiated competitor in the ATTR-CM market—a segment that generates multi-billion-dollar revenue for Pfizer and represents one of the fastest-growing areas in cardiovascular medicine.
Strategic Themes
1. The Regulatory Vacuum Is Now Real, Not Theoretical
On Monday, Makary’s departure was reported but not confirmed. Now it is done. The CNPV program, the Expedited IND, the RTCT pilot, and PDUFA reauthorization are all operating without their institutional champion. Diamantas comes from food safety. Career drug review staff can continue processing standard applications, but commissioner-driven initiatives require active leadership to maintain momentum. Every company with a CNPV filing planned or in progress—Revolution Medicines and Lilly most prominently—needs to assess whether their regulatory strategy assumes a functioning CNPV or builds in contingency for standard review timelines.
2. Three Empty Health Positions Is an Institutional Crisis, Not Just a Leadership Gap
FDA commissioner, CDC director, and surgeon general all vacant simultaneously. The federal health infrastructure that is supposed to oversee drug safety, disease surveillance, and public health communication is operating without confirmed leadership at its three most visible positions. For an industry that depends on regulatory predictability, the combination of leadership vacancies creates an environment where institutional decisions are made by acting officials with limited mandates and uncertain tenures.
3. European Mid-Cap Acquirers Are a New Structural Force in Biopharma M&A
$5.5 billion from Chiesi, Angelini, UCB, and LEO in under a month. The buyer pool for clinical-stage U.S. biotechs now extends beyond American mega-caps and European giants to include mid-sized European pharma companies with focused therapeutic strategies and sufficient balance sheet capacity to execute billion-dollar transactions. For biotech founders and investors, this broader buyer pool improves exit optionality and may support higher acquisition premiums as competition for targets intensifies.
4. Cardiovascular Could Be the Next Growth Vertical
New AHA/ACC guidelines, active PCSK9 investment from Merck and Amgen, BridgeBio challenging Pfizer in ATTR-CM, and broadened lipid-lowering treatment recommendations collectively signal renewed commercial opportunity in cardiovascular medicine. The segment has been overshadowed by oncology and GLP-1 for years. If the guidelines drive meaningful prescribing behavior changes and the pipeline delivers differentiated products, cardiovascular could re-emerge as a primary growth vertical for pharma.
Frequently Asked Questions
Did Makary resign or was he fired?
Makary resigned on Tuesday May 12. The resignation came after multiple outlets reported the previous week that the White House had signed off on a plan to replace him. The immediate trigger was a disagreement over flavored e-cigarette authorization, which Makary opposed. A source told CNN he “doesn’t want to approve youth-appealing flavors, but has been forced to by the powers that be.”
Who is Kyle Diamantas?
The new acting FDA commissioner. Diamantas was deputy commissioner for food and was elevated to be one of Kennedy’s deputy secretaries. He oversees the FDA’s food program and has no known track record on drug development policy.
What happens to the CNPV program?
The program has institutional infrastructure and has approved three NMEs (Foundayo, Otarmeni, Bizengri) plus psychedelic fast-tracks. Revolution Medicines and Lilly T2D filings are planned. Whether the program continues operating at pace during the leadership transition is uncertain. Standard NDA review timelines (10 to 12 months) would apply if the CNPV stalls.
Which health positions are vacant?
Three Senate-confirmed positions: FDA commissioner, CDC director, and surgeon general. All three are simultaneously vacant.
Who might be the permanent nominee?
Stephen Hahn (FDA commissioner 2019 to 2021) and Brett Giroir (former acting commissioner and HHS assistant secretary) have been discussed. Kennedy said the search “is already underway.” Senate confirmation is required (Makary was confirmed 56-44).
What are European mid-caps buying?
Chiesi bought KalVista ($1.9B), Angelini bought Catalyst ($31.50/share), UCB bought Candid ($2.2B) and Neurona ($1.15B), and LEO Pharma bought Replay. Combined deployment exceeds $5.5 billion in the past month. Each company is extending established therapeutic franchises by acquiring U.S. biotechs.
What do the new cardiovascular guidelines mean?
The AHA/ACC guidelines call for more aggressive LDL reduction, focusing on sustained low levels of apolipoprotein B and LDL particles. This could expand the addressable market for PCSK9 inhibitors (Repatha and others) and next-generation lipid-lowering agents. Merck and Amgen are increasing their investment in the space.
What is the BridgeBio ATTR-CM data?
Indirect comparisons showed a numerical survival benefit with BridgeBio’s Attruby versus Pfizer’s tafamidis in transthyretin amyloid cardiomyopathy. Indirect comparisons have significant limitations, but the data position Attruby as a potentially differentiated competitor in a multi-billion-dollar market.
BioMed Nexus Pro — What Institutional Subscribers Are Reading Today
Regulatory Vacuum: Updated Risk Assessment. We reassess every Makary-era initiative—CNPV, Expedited IND, RTCT, PDUFA reauthorization, and FDA staffing—with risk levels updated for the confirmed departure. The Expedited IND is now at very high risk. The CNPV has elevated to high risk. The RTCT pilot is uncertain. We model what each scenario means for companies with active filings.
European Buyer Wave. We analyze why Chiesi, Angelini, UCB, and LEO emerging simultaneously as active acquirers represents a structural shift in the M&A landscape, map which therapeutic areas are most attractive to European mid-caps, and assess what the broader buyer pool means for biotech valuations and exit premiums.
Cardiovascular Opportunity. We assess how the new AHA/ACC guidelines expand the PCSK9 addressable market, analyze BridgeBio’s ATTR-CM positioning against Pfizer, and evaluate whether cardiovascular can re-emerge as a primary pharma growth vertical alongside oncology and GLP-1.
Plus: Diamantas profile, PDUFA reauthorization timeline, permanent nominee assessment, ASCO 17-day countdown, and the updated catalyst calendar through H2 2026.
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