As a wave of patent expirations encroaches upon many of the world’s top drugmakers, companies will need to be diligent in acquiring external products with the potential to launch in the near term. Meanwhile, those pharmas facing greater generic threats in the coming decade may be more inclined to pick up earlier-stage candidates from beyond their own pipelines.

That’s according to a new report from Leerink Partners outlining large pharma companies’ loss of exclusivity (LOE) exposure between both 2025 and 2030, and 2030 through 2040.

In the coming years, Bristol Myers Squibb, Merck, Amgen, Novartis and AstraZeneca are staring down the greatest level of exposure to generic and biosimilar competition while Vertex, Gilead Sciences, Sanofi, Novo Nordisk and Eli Lilly are the least exposed over the 2025-2030 timeframe, Leerink said.

From 2030 onward, however, Lilly, Gilead and Novo are much more likely to take a hit from LOEs, alongside companies like Regeneron and Biogen, the analysts pointed out. Vertex, GSK, Pfizer, Takeda and Amgen are likely to fare the best in terms of LOE exposure from 2030 through 2040, the Leerink team added.

Leerink’s LOE augury accounted for 17 large-cap biopharmas and only included drugs with expected revenue of $1 billion or more in the base years of 2025 or 2030. The analyst team omitted antibody-drug conjugates, CAR-T therapies, vaccines and gene therapies from their projections given the lack of regulatory pathways for generics or biosimilars to those types of medicines.

Naturally, the LOEs for certain drugs in Leerink’s list could be extended through patent expansions or litigation, the analysts caveated. Plus, companies will also need to pursue their own R&D in addition to external innovation, Leerink said.

Still, the overall message of the report is clear: “Companies with sizable LOE exposure in 2025-2030 are under pressure to acquire assets that can be launched in coming years,” while “[t]hose which do not face significant LOEs until 2030+ may be more aggressive acquirers of earlier-stage assets.”

LOEs on the horizon

Bristol Myers Squibb faces the greatest risk of exposure in the near future, with 64% of its estimated revenue in 2025 ($48.3 billion) subject to patent losses and generics through the end of the decade, according to Leerink’s report.

BMS’ blood thinner blockbuster Eliquis, which would account for some 30% of the company’s expected 2025 revenue, faces the biggest threat, with generics poised to hit the scene in the U.S. in April 2028 and by 2026 overseas. Other BMS drugs subject to an LOE hit include Opdivo, which is set to lose U.S. exclusivity at the end of 2028, and Pomylast, expected to lose U.S. patent protection in early 2026, among others, the Leerink team said.

With regards to BMS’ appetite for external innovation, the company is primarily eyeing licensing partnerships and bolt-on acquisitions, with an emphasis on earlier-stage assets, according to a separate Leerink report from October on the biopharma industry’s M&A outlook.

Speaking to analysts on the company’s third-quarter earnings call, BMS CEO Chris Boerner recently pointed to the company’s “financial discipline,” which he figures provides the “flexibility to continue to invest both in our internal program as well as source innovation externally.” 

Boerner highlighted Bristol’s $14 billion acquisition of Karuna Therapeutics last winter as a prime example of the company’s dealmaking acumen. That transaction recently bore fruit thanks to the FDA approval of the companies’ landmark schizophrenia treatment Cobenfy.

Behind BMS, Merck faces the next greatest threat of exposure from 2025-2030 at 47% of its $72 billion in estimated 2025 revenue, the Leerink team said. Naturally, the company’s immuno-oncology cash cow Keytruda is the biggest liability, with a U.S. loss of exclusivity closing in by 2028.

Januvia, Bridion and Lynparza could also prove troublesome for the New Jersey drug giant, with U.S. LOEs slated to hit in 2026 and 2027.

With that in mind, Merck has ample cash on hand to forge deals, with management expressing an appetite for assets across all stages of clinical development, according to Leerink’s M&A report.

“From a capacity perspective, just to be clear, we continue to think we have capacity, frankly, to do pretty much anything of any size,” Merck’s CEO, Robert Davis, said on a recent analyst call. “But our focus area continues to be mainly in that $1 billion to $15 billion range.”

Meanwhile, Merck as of 2024’s third quarter had tripled the number of phase 3 assets in its pipeline from the same period three years ago, “so, we have a lot there, but we need to add more,” Davis said. He added that the company is keeping its eyes peeled for enticing candidates “across all therapeutic areas.”

Amgen faces the next greatest exposure threat at 42% of its predicted 2025 revenue, thanks to LOEs on products like Prolia, Enbrel, Xgeva, Repatha, Otezla and Kyprolis, all of which could face generic or biosimilar rivals by the end of the decade. Notably, the California-based drugmaker settled with Sandoz to allow for biosimilar entries to Prolia—which makes up 10% of the company’s estimated 2025 revenue—and Xgeva—which accounts for 5% of that 2025 sales prediction—to launch at the end of next May.

Amgen’s management has previously stated that the company will need to adapt and allocate capital accordingly in the face of the Inflation Reduction Act (IRA), which it believes has disincentivized investments in areas like small molecules, Leerink noted in its October M&A report.

That said, Amgen is still abuzz about the $27.8 billion acquisition of rare disease drugmaker Horizon Therapeutics that it closed last October, with the pharma’s R&D head and chief scientific officer Jay Bradner, M.D., noting on Amgen’s third-quarter earnings call that the company expects a “blend of internal and external innovation” to “more than replenish the rare disease mid- and early-stage pipeline in the years to come.”