Big Pharma’s patent cliff is no longer a distant problem. More than $500 billion in worldwide prescription drug sales are potentially at risk from generic competition between 2026 and 2032, according to Norstella forecasting data provided by Evaluate.
The risk is not evenly distributed. Merck & Co. is the most exposed in the near term as its cancer immunotherapy blockbuster Keytruda approaches patent expiry in 2028.
AbbVie’s exposure will rise sharply early next decade as the immunology drugs Rinvoq and Skyrizi lose protection. Johnson & Johnson, Sanofi and AstraZeneca will also face meaningful pressure.
Having sales at risk, however, does not mean every dollar disappears. Patent expiry, market geography, the timing of generic or biosimilar competition and lifecycle-management strategies can all influence how quickly revenue erodes.
Still, the numbers illustrate why large drugmakers have spent heavily on dealmaking in recent years to refill pipelines before major blockbusters face competition.
Pharma’s patent cliff builds toward a 2031 spike
By the numbers
$500 billion+
The amount of worldwide prescription drug sales that Evaluate says are potentially at risk from generic competition between 2026 and 2032.
The number underscores the scale of the revenue overhang facing the industry as some of its biggest products move closer to the end of their protected commercial lives. And the exposure is not concentrated in just one year. Instead, the forecast shows a multiyear buildup that stretches from the late 2020s into the early 2030s.
$99 billion
The amount of worldwide sales at risk from patent expiration in 2028 alone, according to Evaluate’s forecast.
That year stands out in part because it’s when Keytruda approaches expiry. Merck has been forced to get creative in the shadow of its oncology mainstay’s impending fall off the patent cliff, turning to new delivery mechanisms like a subcutaneous injectable version of Keytruda approved by the FDA last September.
Evaluate’s data also show that 6.5% of the worldwide prescription drug market is at risk from patent expiry in 2028 — a reminder that the cliff is not just large in dollar terms, but also meaningful relative to the size of the overall market.
$158 billion
The largest single-year exposure in Evaluate’s 2026–2032 forecast, landing in 2031.
The spike shows that the patent cliff does not end with Keytruda. If anything, Evaluate’s numbers suggest the pressure intensifies again in the early 2030s as another wave of large franchises moves toward the end of patent protection.
That broader exposure includes pressure building for several major drugmakers. Evaluate says J&J’s risk escalates in 2027 and 2028 as Imbruvica and Darzalex approach patent end. Sanofi’s Praluent and Dupixent may face competition in 2029 and 2030. AstraZeneca also has a cluster of products facing early-next-decade expiries, including Imfinzi, Tagrisso, Calquence, Farxiga and Saphnelo.
The obesity market, for now, sits farther out. Evaluate notes that Novo Nordisk’s Ozempic is the first of the current obesity blockbusters expected to face competition, while Eli Lilly’s Mounjaro does not come under pressure until the mid-2030s.
~ $50 billion
That’s roughly the one-year sales exposure Evaluate’s figures show for AbbVie in 2032.
AbbVie’s risk rises dramatically in the early 2030s as Rinvoq and Skyrizi — two of the company’s most important growth products — approach the end of protection. That makes AbbVie one of the clearest examples of how the industry’s patent-cliff problem is not confined to older blockbusters; it is also a looming issue for some of pharma’s current growth engines.
The contrast between Merck and AbbVie is especially revealing. Merck is the most exposed in the near term, while AbbVie’s challenge appears more acute slightly later. Together, they illustrate how the patent cliff can unfold in stages rather than all at once.
$30.9 billion
The total value across Merck’s six announced deals since the start of 2024 — the highest spend in Evaluate’s comparison of patent-exposed pharma buyers.
The M&A numbers suggest the industry is not simply waiting for the cliff to arrive. According to Evaluate’s tally, since the start of 2024, Lilly announced $27.2 billion across nine deals — perhaps not surprising given the M&A freedom the windfall from its GLP-1 franchise has afforded the company — followed by AbbVie at $22.3 billion in deals, J&J at $20.4 billion, Sanofi at $16.1 billion and AstraZeneca at $6.8 billion.
Patent pressure is already driving dealmaking
That spending supports a broader point: The patent cliff is not only a revenue-risk story. It is also shaping strategy. Companies facing large future holes in their portfolios are already using business development to soften the blow.
For drugmakers, the cliff is not just a countdown to post-patent competition. It is a test of whether pipeline-building, lifecycle management and M&A can move fast enough to offset the revenue that some of the industry’s biggest products still generate today.
