Even biopharma’s biggest players have been forced to take a hard look at their businesses and realign their cost structures to cope with the continued and compounding challenges plaguing the industry.
In the coming years, Big Pharma will have to reckon with what analyst Mitchell Kapoor calls an “existential risk” to the industry.
“Between 2025 and 2030, the pharmaceutical industry has been slated to face a massive $236 billion to $300 billion patent cliff,” with nearly 70 blockbuster drugs slated to lose market protections, the H.C. Wainwright director and senior biotech equity research analyst explained to BioSpace in an email.
To protect their bottom-lines, companies across biopharma have been forced to realign their priorities and cost structures, resorting to drastically pruning their pipelines and workforces. By the end of 2024, more than 20,000 jobs across biopharma had been eliminated. That number surged 47% in 2025, with some 42,700 employees laid off across the industry, according to a BioSpace tally, with 2026 not looking much brighter.
These are not decisions companies undertake lightly, and they’re not overnight solutions. These reorganization efforts cost millions—maybe even billions—and take months to years of work to execute. But C-suites across biopharma are facing an overlapping series of headwinds that threaten to throw the industry off course, Kapoor said.
Indeed, aside from the looming patent cliff, the industry is still in the midst of a protracted post-COVID normalization, Kapoor said, referring to the capital markets. Despite an uptick in dealmaking and IPOs this year, money flowing into drug development will perhaps never match the capital that poured in during the pandemic. Still today, funders are more risk-averse, preferring to throw their dollars behind programs that are more mature and based on more-established science.
There are other macro-level factors, too, not least of which are the pricing and policy pressures from the government. Drugmakers also face continued instability at the FDA, complicating drug development timelines.
As the storm continues to push the industry around, BioSpace looks at five Big Pharma companies that have enacted sweeping, sometimes-drastic restructuring initiatives to ride it out.
Takeda reels from clinical, commercial setbacks
Takeda kicked off a reorganization program in May 2024, with an eye toward “organizational agility, spending efficiencies and leveraging the company’s capabilities in data, digital and technology.”
At the time, the Japanese pharma had just suffered a more than 50% hit to its profit. For the fiscal year 2023 (which ran from April 2023 through March 2024), Takeda’s operating profit came out to 214.1 billion yen ($1.3 billion), down from 490.5 billion yen ($3.1 billion) the year prior.
In October 2023, the Japanese multinational was forced to pull its lung cancer drug Exkivity from pharmacy shelves worldwide after disappointing findings from a Phase 3 confirmatory study. Later that month, Takeda’s cell therapy Alofisel also failed a late-stage study for Crohn’s perianal fistulas. These back-to-back stumbles resulted in a $770 million write-down for Takeda and a 71% cut to 2023 profit projections.
Takeda’s restructuring effort has meant thousands of layoffs across its business. After kicking off the campaign in mid-2024, the company let go of more than 1,500 employees that year. Last month, Takeda announced that 4,500 more workers would lose their jobs during the 2026 fiscal year.
Aside from layoffs, the pharma has also made notable changes to its pipeline and drug development strategy. In October last year, Takeda pulled away from cell therapies completely, offloading the programs to an external partner. This move included a headcount reduction of 137.
Then in April, the pharma pulled the plug on a dementia drug candidate that had been under development with Denali Therapeutics due to “strategic considerations,” the biotech said in an SEC filing at the time. The partners had also previously been working on an Alzheimer’s disease program that was discontinued in August 2023.
Pfizer struggles to regain bearing in post-pandemic market
Pfizer was one of the pandemic’s biggest winners, developing the COVID-19 vaccine Comirnaty in collaboration with BioNTech, which in 2021 became the world’s top-selling pharma product with nearly $38.6 billion in revenue. Once the virus hit endemic status, however, market demand for the shot cratered, bringing down Pfizer’s revenues along with it.
In October 2023, after suffering quarter after quarter of declining revenues, the pharma launched a “multi-year, enterprise-wide cost realignment program.” The goal, Pfizer said at the time, was to reduce cash burn by $1 billion that year plus an additional $2.5 billion in 2024. In May 2024, the company added $1.5 billion to this savings target through 2027 and in April 2025 raised the bar by $1.7 billion more.
Shortly after launching the restructuring, the pharma suffered a series of clinic losses. In December 2023, the company’s former obesity bet danuglipron ran into safety issues, forcing Pfizer to discard its investigational twice-daily regimen for the GLP-1 pill. The pharma pushed through with a daily, modified-release version of the drug, but that formulation was also beset with liver toxicities, ultimately prompting Pfizer to scrap danuglipron altogether.
Aside from pandemic and pipeline problems, Pfizer is also facing a strong patent headwind, with the Bristol Myers Squibb–partnered anticoagulant Eliquis set to lose key market exclusivities this year.
“Restructuring improves margins, but the market ultimately wants a long-term vision into what replaces the old growth base,” Ram Selvaraju, managing director and senior healthcare equity research analyst at H.C. Wainwright & Co., told BioSpace in an email. For Pfizer, this will involve showing investors that new pipeline bets—built with the bounties of several big-ticket acquisitions, such as the $43 billion acquisition of Seagen and $9.8 billion takeover of Metsera—"can carry more” in terms of generating revenue as the company’s vaccine business finds its post-COVID groove, Selvaraju said.
Even with a stacked portfolio, however, Pfizer’s path to recovery looks to be a long one, with the pharma expecting momentum to shift in its favor starting 2029.
BMS faces one-two patent punch
For Bristol Myers Squibb, a sweeping strategic reorganization and ambitious cost-cutting offered a way to soften the blow from a looming patent cliff.
Two of the pharma’s biggest money-makers are set to come under biosimilar attack in the coming years. The Pfizer-partnered blood thinner Eliquis, which last year reigned as BMS’ top-earner with worldwide revenues of $14.4 billion, will lose key protections this year—and its impact on BMS’ topline will be severe. GlobalData in February forecasted that sales of the drug will crash by 15.2% in 2026.
Also nearing the end of its exclusivity is the checkpoint inhibitor Opdivo, BMS’s second-biggest product. Opdivo, indicated for a variety of cancers, made $10.05 billion globally in 2025 but is facing key patent expirations in the U.S. by 2028.
In the first quarter of 2024, BMS rolled out a “strategic productivity initiative” aimed at streamlining operations and cutting back cash burn. The pharma set an initial savings target of $1.5 billion through 2025, which would be met by eliminating 2,200 roles across the enterprise.
BMS in February 2025 added $2 billion to the cost-cutting goals, to be realized through the end of 2027. Aside from layoffs—of which there have been several rounds—the pharma’s strategic push has also come at the cost of terminated partnerships and culled assets.
But BMS’ efforts go beyond simple cost-cutting and includes deals that could position it for greater growth. Just months before unwrapping the strategic campaign, for instance, BMS swallowed neuro specialist Karuna Therapeutics for $14 billion and acquired radiopharma-focused RayzeBio for $4.1 billion.
Other partners that the pharma has since brought on via licensing deals include BioNTech and Hengrui Pharma.
As in Pfizer’s case, the success of BMS’ reorganization will depend heavily on how well these pickups are executed, Wainwright’s Selvaraju explained to BioSpace in an email. “It means scaling newer growth drivers quickly enough to offset” the impending erosion of the company’s current cornerstone products, he said.
Outmaneuvered by main competitor, Novo doubles down on core expertise
Just over a year ago, Novo Nordisk’s leadership shocked the industry by ousting former CEO Lars Fruergaard Jørgensen, who had ushered the pharma to a position of global renown with the help of the blockbuster GLP-1 franchise semaglutide. Despite being the first pharma company to market a GLP-1 therapy, the Danish drugmaker has been clinically and commercially outmaneuvered by rival Eli Lilly.
Jørgensen’s exit—which the pharma said at the time was precipitated by “the recent market challenges Novo Nordisk has been facing”—would jumpstart a sweeping business realignment initiative.
“We need to reallocate and look at our cost base and really put the money where the growth is,” new CEO Maziar Mike Doustdar, told investors during the pharma’s Q2 2025 earnings call.
Just over a month later, the Danish giant announced that it would say goodbye to some 9,000 employees across global operations, with the goal of saving roughly $1.25 billion through the end of this year. The layoffs represent a downsizing of Novo’s worldwide headcount by 11%.
Novo has also abandoned all work in cell therapy, announcing the pivot less than two weeks after Takeda did the same.
Novo at the time said that the savings from all the changes would be “redirected to growth opportunities in diabetes and obesity” as the company tries to minimize Lilly’s lead. Last year, Lilly’s tirzepatide franchise, branded as Mounjaro for type 2 diabetes and Zepbound for obesity, together brought in $36.51 billion. Semaglutide—which includes Ozempic for diabetes, Wegovy for weight loss and the older-generation Rybelsus—earned $36.19 billion.
The weight-loss war has now moved to the next phase, waged by oral assets. So far, Novo looks to be well-positioned, with the Wegovy pill once again beating Lilly’s Foundayo to the market—and delivering sales that have exceeded analyst expectations.
Merck a ‘good example’ of bracing for cliff
Merck is what Wainwright’s Kapoor considers a “good example of how large pharma can defend a franchise without betting on only one answer.”
He’s talking about Keytruda, the mega-blockbuster franchise that for three years running has reigned as the industry’s most valuable product. Last year, Keytruda—approved for more than 40 indications—brought in nearly $32 billion. But key market protections for the PD-1 blocker are expiring in 2028, and Merck is bracing for the fall.
In July last year, the pharma announced a $3 billion savings campaign through 2027, which has so far involved several rounds of layoffs across its global footprint. Merck intends to put these savings back into its business to support product launches and areas of higher growth.
Instead of looking for that one successor to Keytruda, Merck has instead been “building a broader defense” of its business, Kapoor told BioSpace—a strategy that he thinks is a smart way of developing the next phase of the pharma’s pipeline.
One area Merck has been investing in is the PD-(L)1/VEGF wave, betting up to $3 billion in November 2024 to partner with Shanghai’s LaNova Medicines. Summit Therapeutics and its Chinese collaborator Akeso shook the field in September 2024 when they claimed victory over Keytruda for the PD-(L)1/VEGF bispecific antibody ivonescimab, touting superior progression-free survival in a Phase 3 non-small cell lung cancer study.
But Merck has also been looking at other cancer modalities, particularly ADCs. Merck is working with Kelun-Biotech to advance a combo regimen of Keytruda with the TROP2 ADC sac-TMT in lung cancer.
Data earlier this month showed that the doublet achieved a “clear advantage” in overall survival over Keytruda alone, suggesting that the pharma “may be able to defend the Keytruda backbone aggressively with an ADC combination rather than cede the next lung cancer chapter to PD-1/VEGF challengers,” Kapoor said.
“That is the kind of portfolio logic large pharma wants right now,” he continued—“multiple shots around a core franchise, not one binary replacement bet.”
