If ultimately confirmed, Makary’s planned departure, broken by The Wall Street Journal Friday afternoon, would follow a controversial tenure in which his deputy and constant co-author Vinay Prasad riled biopharma feathers with myriad unexpected drug rejections. Prasad stepped down as biologics chief last week.

President Donald Trump has reportedly signed off on a plan to fire FDA Commissioner Marty Makary, who has overseen a tumultuous period at the agency defined by unexpected drug rejections, staff departures and reported infighting among leadership.

The news, reported by The Wall Street Journal Friday afternoon, citing “people familiar with the matter,” comes after Makary defended one of those controversial rejections—that of Replimune’s advanced melanoma therapy RP1—in a heated interview with CNBC on Tuesday. Other unexpected rejections during the past year include Capricor Therapeutics’ deramiocel for Duchenne muscular dystrophy cardiomyopathy last summer, and Disc Medicine’s rare disease drug bitopertin, which was awarded a Commissioner’s National Priority Voucher (CNPV) in October 2025.

Makary took over the FDA leadership role on March 25, 2025, after congressional confirmation. He previously served as a surgical oncologist at Johns Hopkins University School of Medicine.

While he was head of the agency, Makary often faded into the background behind larger personalities, such as Center for Biologics Evaluation and Research Director Vinay Prasad. Prasad left the FDA on April 30 at the end of an apparently planned one-year leave of absence from the University of California, with Katherine Szarama put in his place as acting director—the fifth leader of CBER in less than 18 months.

Makary also came under fire after the FDA refused in February to review an application for Moderna’s mRNA-based flu vaccine. Makary was called to the White House and Trump “expressed frustration” to Makary over how the agency is handling vaccine issues, Politico reported at the time, citing two people privy to details about the meeting. The FDA accepted an amended application for the vaccine a week later.

Trump’s plan is not final and could change, WSJ noted.

“President Trump has assembled the most experienced and talented administration in history, an administration that continues to focus on delivering more historic victories for the American people,” White House spokesman Kush Desai told the publication.

BioSpace has reached out for independent confirmation.

One of Makary’s more controversial ideas is the Commissioner’s National Priority Voucher (CNPV) program, which is meant to grant swift reviews to hand-selected therapies. The program, however, has been met with legality concerns. Questions were also raised about the efficacy of the scheme in February after bitopertin was rejected.

Veteran regulator Richard Pazdur pointed to pressure from Makary as one of the concerns that led to his resignation as head of the FDA’s Center for Drug Evaluation and Research in December 2025.

Pazdur has since spoken out about his experience, claiming that the “wall between the commissioner’s office and the review staff has been breached” under Makary’s leadership.

Makary was a frequent figurehead at the White House as President Donald Trump announced policies related to health or drug pricing. He attended the Most Favored Nation drug pricing announcements in the fall as major pharmaceutical companies, including Pfizer, Eli Lilly and Novo Nordisk reached agreements to lower prices for some of their medicines.

In November 2025, reports emerged that the Trump administration was considering limiting Makary’s role or replacing him entirely. He seems to have survived that review until now.

The German mRNA specialist BioNTech made a fortune through its alliance with Pfizer. BioNTech launched “Project Lightspeed” in January 2020, days after the SARS-CoV-2 genetic sequence went public. It received €375M from the German government to accelerate development and production. Pfizer declined U.S. government support in the form of Operation Warp Speed R&D funding to preserve scientific independence. Yet the U.S. government placed a $2 billion advance-purchase order for 100 million doses in July 2020, with hundreds of millions more to follow. That purchase guarantee, combined with emergency use authorization in December 2020, helped turn Comirnaty into one of the best-selling pharmaceutical products in history. Comirnaty generated roughly €36B in BioNTech revenue across 2021 and 2022.

In the wake of the pandemic, demand went into freefall. BioNTech’s revenue fell from €19B in 2021 to €118M in the first quarter of 2026. Meanwhile, the political ground shifted beneath the entire mRNA sector. In August 2025, HHS Secretary Robert F. Kennedy Jr. terminated 22 BARDA mRNA vaccine development investments, rejecting the platform outright. The wind-down hit companies and institutions across the sector: contract terminations for Emory University and Tiba Biotech, de-scoping of mRNA work with Luminary Labs, ModeX and Seqirus. It also rejected pre-award proposals from Pfizer, Sanofi Pasteur, CSL Seqirus, Gritstone and others. Kennedy said the data showed mRNA vaccines “fail to protect effectively against upper respiratory infections like COVID and flu.” Researchers at Johns Hopkins, Harvard and the National Academy of Medicine disagreed with those conclusions. But it was clear in 2025 that Trump 2.0, whose prior administration helped support the mRNA vaccine market through Operation Warp Speed purchase commitments, was now actively steering federal dollars away from the technology.

Against such headwinds, BioNTech moved to consolidate. In June 2025, it announced the acquisition of CureVac, a fellow German mRNA company, for $1.25B in stock. CureVac had its own pandemic arc. Its first-generation COVID-19 vaccine candidate showed just 48% efficacy in a Phase 3 trial in 2021. The company, and its partner Bayer, abandoned COVID-19 development as rivals hit the market. CureVac refocused on next-generation mRNA platforms, partnering with GSK. BioNTech called CureVac’s research and manufacturing site in Tübingen a “major prize,” per Fierce Biotech.

Five months after that deal closed, BioNTech announced it is shuttering the Tübingen site, along with facilities in Idar-Oberstein, Marburg and Singapore. In all, some 1,860 jobs will be shed. In addition, BioNTech is exiting in-house COVID vaccine manufacturing entirely, handing all production to Pfizer. The closures are expected to save €500M annually by 2029.

BioNTech still has €16.8B in cash and a bet-the-company oncology pivot, with 15 Phase 3 trials planned by year-end and seven late-stage data readouts expected in 2026. It expects zero oncology revenue this year. In the same earnings call that announced the layoffs, BioNTech also approved a $1B share buyback program.

After a period of post-pandemic hibernation, where growth was uneven, one closely watched measure of biopharma R&D productivity is moving in the right direction. According to the 16th edition of Deloitte’s annual Measuring the Return from Pharmaceutical Innovation report, which is tellingly titled “Navigating the GLP-1 boom,” the projected internal rate of return on late-stage pipeline assets rose for the third consecutive year, hitting 7.0% in 2025. That’s a jump from 5.9% the year before. The sector, it seems, has transitioned from winter to spring. “We went through a period of so many years where the returns kept declining, excluding the COVID impact in the middle,” said Kevin Dondarski, principal for life sciences strategy at Deloitte Consulting. “But the increase over the last few years is analytically unprecedented.”

The catch? Much of that growth in 2025 traced back to a single class of therapies. GLP-1/GIP drugs targeting obesity and related metabolic conditions now account for an estimated 38% of all projected commercial inflows from the 2025 late-stage pipeline. Strip them out, and headline internal rate of return (IRR) falls from 7.0% in 2025 to 2.9%. For the sake of comparison, IRR was 5.9% in 2024 and without GLP-1/GIP drugs, it was 3.8%. “There are two different messages here,” Dondarski said. “One, it’s certainly attractive, because the market is valuing the potential impact that those therapies can have on the public, which is great. But at the same time, it raises the question of sustainability. As those programs progress, is there going to continue to be that opportunity through the next generation and the next? It will create a responsibility for these companies to find the right assets to replace in the pipeline.”

When asked if removing one drug class had ever flipped the direction of the headline IRR number, Dondarski said this year was the most dramatic example the report has ever seen over its 16 year history. “There tends to be a certain set of classes that account for a lot of value; if you take them out, the IRR goes down. But this is the largest impact that I think we’ve seen in the history of our work.”

Average forecast peak sales per pipeline asset jumped to $598 million in 2025, but the spread tells the real story: the top performer now approaches $5 billion while the “without GLP-1s/GIPs” marker sits at $353 million, actually lower than the year before. Strip out the obesity blockbusters and underlying pipeline productivity is declining. Source: Deloitte, “Navigating the GLP-1 boom,” 2026.

Investors have been getting mixed signals about the durability of the GLP-1/GIP boom. Since the beginning of the year, tirzepatide (marketed as Zepbound and Mounjaro) developer Eli Lilly, which launched its oral GLP-1 orforglipron (marketed as Foundayo) in April 2026, has seen its stock skid roughly 10-13% year-to-date, even as it raised full-year revenue guidance to $82-$85 billion on the strength of Mounjaro and Zepbound volume growth. In 2025, Novo Nordisk swapped longtime CEO Lars Fruergaard Jorgensen with Maziar Mike Doustdar amid slowing momentum and share-price pressure. Seven board members stepped down at a November 2025 extraordinary general meeting, and the company announced plans to cut about 9,000 roles from a global workforce of 78,400. Novo’s Q1 2026 release says the company employs about 67,900 employees, implying roughly 10,500 fewer than the 78,400 workforce cited when the restructuring was announced. Adding to the pressure, Novo had hoped CagriSema, a combination of the amylin analogue cagrilintide and semaglutide, would drive future growth. Instead, the drug failed to show non-inferiority against Lilly’s Zepbound in the REDEFINE 4 Phase 3 head-to-head trial reported in February 2026, delivering 23.0% weight loss versus 25.5% for tirzepatide, triggering another wave of investor disappointment.

Are obesity drugs the golden goose?

Despite the turbulence, strong demand for GLP-1s persists. Lilly delivered a clean Q1 beat, while Novo’s quarter showed a more complicated version of strength: rapid Wegovy pill uptake and a profit beat alongside lower adjusted sales. Lilly reported revenue of $19.8 billion (versus $17.6 billion expected), a 56% year-over-year increase driven by Mounjaro at $8.7 billion (+125%) and Zepbound at $4.1 billion (+79%). Lilly raised full-year revenue guidance by $2 billion, to $82-$85 billion. Novo reported Q1 sales of DKK 96.8 billion ($15.2 billion), with its oral Wegovy pill, launched January 5, generating DKK 2.26 billion in its first quarter, nearly double the DKK 1.16 billion analysts had expected. But the underlying tension persists: Lilly’s 56% revenue growth was driven by a 65% volume increase partially offset by a 13% decline in realized prices, and Novo’s adjusted sales still fell 4% at constant exchange rates once a one-time $4.2 billion 340B provision reversal was excluded.

On top of all of this, both Eli Lilly and Novo Nordisk have agreed to lower U.S. prices for GLP-1s through Medicare, Medicaid and TrumpRx. Under the November deal, Medicare and Medicaid coverage for weight-loss use was expected to expand for the first time, with $50 monthly copays for eligible beneficiaries. The live TrumpRx site now lists Wegovy pill at $149 per month, Wegovy pen at $199, Ozempic at $199 and Zepbound at $299.

The spiraling cost of R&D

Obesity now commands the largest share of late-stage pipeline value (24.7%), displacing oncology (20.3%) for the first time in the report’s 16-year history. But the concentration within obesity is even more striking: nearly 96% of that value sits with just three companies. Source: Deloitte, “Navigating the GLP-1 boom,” 2026.

The report also found that the average cost to develop a drug from discovery to launch grew to $2.67 billion in 2025, up from $2.23 billion the year before. Dondarski said the team investigated whether a single outlier explained the spike. “We saw the cost increase for 17 out of the 20 companies, so it was a persistent theme,” he said. Three factors converged, including R&D costs continuing to rise above general inflation, large-scale M&A deals inflating the R&D cost base, and attrition shrinking the overall number of late-stage programs by roughly 4-5%.

AI: still waiting for liftoff

Last year’s edition of the Deloitte report was titled “Be brave, be bold” and urged pharma companies to embrace AI-powered drug development platforms, automation and advanced analytics as a path to reversing decades of declining R&D productivity. Despite that call to action, the 2025 data shows R&D costs climbing to a record $2.67 billion per asset while clinical cycle times remain stubbornly long. The report now concedes that AI’s promise to significantly reduce development time and costs “has not yet been realized at scale, largely due to a pilot-driven, function-by-function approach.”

That is not to say AI experience is for nought. “Everybody’s actively focusing on AI, and everybody’s had some degree of success,” Dondarski said. “But from our vantage point, there’s a good amount of variability in the velocity at which organizations are scaling those efforts to maximize value creation.”

Researchers at University of California, San Francisco and Imperial College London have shown that a single dose of psilocybin, the psychedelic compound found in magic mushrooms, causes likely anatomical brain changes that last for up to a month after the experience.

The study, involving healthy volunteers who had never taken a psychedelic, links temporary shifts in brain “entropy”—which is the diversity of neural activity occurring in the brain—to insight. This suggests the psychedelic trip itself is important to the drug’s longer term therapeutic effects.

The researchers found that a high dose of psilocybin led to increased entropy in the minutes and hours after taking the drug. The degree of entropy predicted how much insight, or emotional self-awareness, the participants felt the next day; and this, in turn, forecasted improvements in their sense of wellbeing a month later.

The findings may help to explain psilocybin’s therapeutic effects on conditions such as depression, anxiety, and addiction. “Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, PhD, the Ralph Metzner distinguished professor of neurology at UCSF. “Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health. It suggests that the trip—and its correlates in the brain—is a key component of how psychedelic therapy works.”  Carhart-Harris is senior and corresponding author of the team’s published paper in Nature Communications, titled “Human brain changes after first psilocybin use.”

“Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown,” the authors wrote. Psilocybin is the precursor of the compound psilocin, a serotonin receptor agonist. “Converging evidence supports a role for serotonin 2A receptor (5-HT2AR) agonism in eliciting the characteristic brain and subjective effects of this and related psychedelics in humans,” the team continued.

For their newly reported study, Carhart-Harris and colleagues carried out an exploratory, placebo-controlled, within-patient study in 28 psychedelic-naïve participants who each received a single, high-dose (25 mg) of psilocybin. The researchers used an assortment of brain imaging and brain measurement techniques, some of which were carried out during the peak of the psychedelic experience, as well as before and one-month after drug administration. “This was an exploratory, hypothesis-generating mechanistic study in healthy volunteers,” the authors noted. None of the 28 people in the study had a diagnosed mental health condition, which gave the scientists greater freedom to do more testing.

In the first part of the experiment the subjects were given a 1 mg dose of psilocybin, which the researchers regarded as a placebo, and were then monitored with EEG, which records brain activity from electrodes on the scalp.  Over the next few weeks, the researchers measured their subjects’ psychological insight, wellbeing, and cognitive ability. They examined brain activity with functional MRI (fMRI) and brain connectivity with diffusion tensor imaging (DTI).

One month after the placebo, the subjects were given 25 mg of psilocybin, a dose capable of eliciting a strong psychedelic trip. During the experience, researchers again measured the subjects’ brain activity with EEG, and in the following weeks they repeated the same tests they had given after the 1 mg dose.

This enabled the scientists to compare the effects of the psychedelic trip on the brain and mind to the effects of the placebo. “The multimodal neuroimaging design allowed us to observe changes in brain function and (potential) anatomy from 1-h (EEG) to 1-month (DTI) after high-dose psilocybin,” they explained.

The investigators found that within 60 minutes of taking the 25 mg dose of psilocybin, EEG revealed higher entropy, suggesting that the brain was processing a richer body of information under the psychedelic. A month later, the researchers looked at their subjects’ brains using DTI, which measures the diffusion of water along neural tracts in the brain, and found that they were denser and had more integrity. This is the opposite of what happens in aging, which makes these tracts more diffuse.

The researchers cautioned that more work needs to be done to better understand the meaning of this finding, but the result is a never-before-seen sign of how psychedelics can change the brain. ”The inclusion of DTI enabled us to test for long-term changes in the integrity of white matter tracts post psilocybin,” the authors stated. “Results revealed decreased axial diffusivity in prefrontal-subcortical tracts 1-month post 25mg psilocybin.”

The day after the 25 mg dose, all but one of the 28 subjects rated the trip as the “single most” unusual state of consciousness they had ever experienced. The remaining person rated it as among their top five. The study participants said they had experienced more psychological insight after taking the 25 mg of psilocybin than they had after the 1 mg placebo.  The subjects also reported increased wellbeing two and four weeks after the study. This was measured from responses to statements such as, “I’ve been feeling optimistic about the future,” and “I’ve been dealing with problems well.”

As the scientists noted in their paper, “A predictive relationship was also found between brain entropy and longer-term mental-health changes—namely, improved wellbeing. Improved wellbeing could be predicted directly from acute increases in brain entropy as early as 1-h post dosing.”

A month after the study the study individuals also scored better on a test of cognitive flexibility.  “Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought,” said first author Taylor Lyons, PhD, a research associate at Imperial College London. “The fact that these changes track with insight and improved well‑being is especially exciting.”

The scientists found that the subjects who had experienced the largest increases in brain entropy in the minutes to hours after taking psilocybin were the most likely to have increased insight the next day and increased wellbeing a month later. The researchers concluded that improved wellbeing was driven by the experience of insight.

The authors suggest that the study findings could improve treatment for people with mental illness using psilocybin, for example, by ensuring that the right dosage is used to produce the right amount of brain entropy to promote insight. “We already knew psilocybin could be helpful for treating mental illness,” Carhart-Harris said. “But now we have a much better understanding of how.”

In their paper the team concluded, “The present multi-modal neuroimaging study in healthy participants sheds light on the brain effects of first-time high-dose psychedelic use and the therapeutic action of psilocybin-therapy, suggesting that therapeutically relevant changes—i.e., improved wellbeing—can be forecast via an acute human brain action, i.e., an entropic brain effect, that is well-known to relate to the psychedelic experience … Results support a role for psychological insight in mediating the causal association between the entropic brain effect and potentially enduring improvements in wellbeing.”