With Keytruda, the best-selling drug in the world, facing the end of exclusivity in 2028, BioSpace looks at five drugs that have taken the leap off the patent cliff.
Big Pharma is staring down the barrel of blockbuster patent expirations over the next few years. Merck’s Keytruda, for example, is far and away the best-selling drug on the planet at the moment, clocking in at nearly $30 billion in worldwide sales in 2024, but will go off patent in 2028, and the industry is now racing to develop biosimilars to get a piece of the enormous PD-1 market share.
Like many companies facing substantial loss of revenue due to loss of exclusivity, Merck is doing what it can to protect Keytruda. The pharma company has filed at least 129 patents since Keytruda’s initial approval in 2014, most of which cover new indications and formulations for the drug, rather than the drug itself. This so-called patent thicket could theoretically push its protection into 2036. The company’s patent dance has prompted investigation from the office of U.S. Sen. Elizabeth Warren, D-Mass., to investigate what she called Merck’s “monopoly power.”
Meanwhile, Novo Nordisk is taking a similar tack, building out a complex web of nearly two dozen patents for its blockbuster diabetes drug Ozempic, which came in second on last year’s list of top-selling drugs with nearly $17 billion in sales. Novo has a little more breathing room before Ozempic, also marketed as Wegovy for weight loss, faces generic competition. While the first round of core patents are set to expire in 2026, a secondary group will give Novo exclusivity until 2033.
But if history is any guide, losing exclusivity is not always the death knell of a drug’s profitability. Here, BioSpace explores the sales trajectories of recent blockbuster drugs, before and after they lost their patent, to search out a pattern in the post-exclusivity drug world.
GSK’s Advair
- Indication: COPD and asthma
- Peak Sales: $7.9 billion in 2013
- Year of Patent Expiry: 2010
A new generation of asthma and COPD treatment arrived in the 1990s and 2000s, with Boehringer Ingelheim and AstraZeneca scooping up billions of dollars in sales with their inhalers. But GSK’s multi-blockbuster treatment Advair beat them all when it hit the market in 2000, becoming the best-selling asthma drug on the market at its peak.
The drug lost its patent in 2010 but kept selling steadily for years afterward, hitting peak sales of about £5.27 billion ($7.9 billion) in 2013. GSK’s secret sauce was the specialized Diskus device for administering the drug that had its own separate patent kept generics out until 2019. Generic drugmakers had to find their own device to match with the medicine, which proved difficult for several years. Because of that, “it’s not going to be a classic generic collapse,” analyst Paul Diggle predicted to Reuters in 2010, but rather a “fairly slow collapsing pack of cards.” The data show exactly that.
AbbVie’s Humira
- Indication: Rheumatoid arthritis, psioriasis, ulcerative colitis, other immune-related diseases
- Peak Sales: $21.2 billion in 2022
- Year of Patent Expiry: 2022
Before the earth-shaking numbers that Keytruda put up, AbbVie’s arthritis drug Humira was the reigning champ. After gaining approval in 2008, AbbVie racked up indications in immunology and ran up to peak sales of more than $21 billion in 2022.
The drug’s original patent was set to expire in 2016, but AbbVie for years fought off biosimilars through a blizzard of patents—totaling more than 250 for a variety of indications beyond its original intended use in arthritis. That extended the drug’s runway to 2022, when it finally lost exclusivity in the U.S. That extra time gave AbbVie the opportunity to set up two successor drugs: Skyrizi, which AbbVie bought from Boeringer Ingelheim in 2016 for $595 million, and Rinvoq, which AbbVie developed in-house.
Together, Skyrizi and Rinvoq have almost made up for Humira’s dive off the patent cliff, totaling about $19 billion in sales in 2024. AbbVie expects Skyrizi and Rinvoq to hit a combined $27 billion in sales by 2027.
Amgen’s Neulasta
- Indication: Immune stimulation in chemotherapy patients
- Peak Sales: $5.8 billion in 2013
- Year of Patent Expiry: 2015
Amgen’s blockbuster drug Neulasta—used to stimulate neutrophil growth primarily in patients undergoing chemotherapy—was an annual top 10 best-selling drug for most of its exclusivity period and perennially one of Amgen’s top sellers, going neck-and-neck with Amgen’s arthritis treatment Enbrel.
Amgen didn’t use any special legal maneuvers to prolong the drug’s life after the patent dropped in 2015 (aside from suing potential competitor Coherus, accusing it of poaching Amgen employees to learn about Neulasta). Amgen got lucky that companies jostling to produce their copycats struggled to gain FDA approval. Mylan finally got a biosimilar across the line in 2018, taking a bite out of Amgen’s sales. Sandoz followed in 2019, pushing sales down further.
Pfizer’s Lipitor
- Indication: High cholesterol
- Peak Sales: $12.9 billion in 2006
- Year of Patent Expiry: 2011
Lipitor had an outsized impact on the cardiology space. Its class of drugs—statins —were prescribed to more than 800 million people in 2019, with Lipitor and its generics accounting for nearly 300 million of those. After losing its patent back in 2011, Lipitor fell off a nearly picture-perfect patent cliff when generics immediately cut Pfizer’s sales of the drug by two-thirds in a single year.
Pfizer spun off Lipitor and another legacy drug, Viagra, into a separate company, Viatris, in 2020, which has reported steady total sales of the drug of around $400 million per year for the last few years. Pfizer began selling its own Lipitor generic starting in 2011 in partnership with Watson Pharmaceuticals.
Johnson & Johnson’s Remicade
- Indication: Crohn’s disease, rheumatoid arthritis
- Peak Sales: $6.9 billion in 2016
- Year of Patent Expiry: 2016
The TNFa-blocking antibody Remicade was a blockbuster year after year for J&J’s pharmaceuticals unit Janssen. It’s one of the top five best selling drugs of all time, and the rheumatoid arthritis treatment hit its peak sales in 2016, going head-to-head with Humira in the space.
J&J spent practically the entire lifetime of the drug fighting tooth and nail to maintain patent exclusivity and protect its margins. In 2018, two lawyers from Brinks Gilson & Lione wrote in the National Law Review that J&J had tried and failed to “rewrite history” with the games it played regarding Remicade’s patent.
Pfizer, meanwhile, gambled on the drug’s patent expiring as planned in 2018, launching a biosimilar version in 2016. When a judge temporarily struck down Remicade’s patent, Pfizer sued J&J in 2017 for anti-competitive practices—litigation that was only resolved in 2021. In the end, Remicade’s patent expired on time in 2018, and a suite of additional biosimilars stepped into the space, sending the Remicade’s sales plummeting.
