In the early 2010s, a new phenomenon hit the pharmaceutical industry – the patent cliff. While pharma companies have dealt with the effect of patent expirations since the beginning of patent law, the huge wave of expiries that began in 2011 had a different level of impact. In November 2011, four drugs (Lipitor [atorvastatin], Caduet [amlodipine/atorvastatin], Combivir [lamivudine/zidovudine], and Solodyn [minocycline extended-release tablet], which were worth over $7 billion in sales, lost protection. Between 2007 and 2017, the ten highest value patent expiries resulted in a loss of over $915 billion in lifetime sales for the developers. Over 2025, the industry faces a new wave of patent expirations, including a number of high value diabetes drugs. [1-3]
An introduction to pharmaceutical patents and exclusivity
Patent law is complex and differs across countries. Using the US as an example, a patent lasts for 20 years after the date of application. Drugs are also given exclusivity periods following marketing approval, depending on the type of drug and disease, in order to encourage development and support return on investment, particularly in certain areas of unmet needs such as antibacterials, rare diseases and drugs for infants and children: [4]
Orphan drug exclusivity (ODE) – 7 years
New chemical entity exclusivity (NCE) – 5 years
Generating Antibiotic Incentives Now (GAIN) exclusivity– 5 years added to certain existing exclusivities
New clinical investigation exclusivity – 3 years
Paediatric exclusivity (PED) – 6 months added to existing patents/exclusivity
Patent challenge (PC) – 180 days (this exclusivity is for ANDAs [abbreviated new drug application] only)
Competitive generic therapy (CGT) – 180 days (this exclusivity is for ANDAs only)
Once a drug loses patent and exclusivity protection, the market opens up to generic (small molecule) and biosimilar (biologics) competition. This drives income down in two ways – the originator drug can lose market share to the generic or biosimilar, and the originator price may be reduced to try to compete. As a result, the originator company's revenues can decline by as much as 90%, and market share by as much as 80%. [5]
Products losing protection during 2025
There are a lot of therapeutics losing protection in 2025. This section briefly outlines a number of those, but is by no means inclusive. [6, 7]
Regeneron and Bayer’s Eylea (aflibercept), a VEGF inhibitor, was approved for wet age-related macular degeneration in 2011, with further approvals for diabetic retinopathy plus diabetic and nondiabetic macular oedema. Sales in 2023 were $9.37 billion.
AztraZeneca’s Farxiga (dapagliflozin), an SGLT2 inhibitor, was approved for the treatment of type 2 diabetes in 2014. In 2023, sales were $5.96 billion.
Boehringer Ingelheim’s Jardiance (empagliflozin), also an SGLT2 inhibitor for the treatment of type 2 diabetes, was approved in 2014. Sales in 2023 were around $8 billion. Alembic already has approval for a generic formulation, with an expected launch in 2029.
Bayer, Johnson & Johnson’s Xarelto (rivaroxaban), a factor Xa inhibitor was approved to treat and prevent blood clots in 2011. Sales in 2023 were $4.5 billion. There have been a number of patent disputes, but these have been settled.
Boehringer Ingelheim’s Trajenta (linagliptin), a DPP-4 inhibitor, was approved in 2011 for type 2 diabetes. Sales were $1.7 billion in 2022. The US patent will expire in 2025, but patents elsewhere will remain active until 2033. [8]
Patent expiries beyond 2025
Novo Nordisk’s Ozempic (semaglutide), a GLP-1 receptor agonist, was first approved for type 2 diabetes in 2017, and for weight management in 2021. Sales in 2023 were worth around $14 billion. The US patent is due to expire in 2032, but the China patent expiration is due in 2026. A number of Chinese generics are expected to launch in China between 2025 and 2027. While the market for the weight management form (Wegovy) is likely to remain buoyant, the loss of Ozempic sales is expected to hit the company hard. [9]
Further patent expiries are expected in 2026 and beyond, including some significant oncology expiries: [7]
o Approved 2009-2010 for use in infants
o Market boosted by the recommendation for vaccination in adults over 65 in the US in 2015
o Key patent expiration 2026
o Approved for breast cancer in 2015
o Generic filings made in 2019, but protection extended to 2027
o Already facing competition
o Approved to treat type 2 diabetes in 2014
o Key patent expiration 2027
o 17th bestselling drug in the world in 2023
o Approved to prevent blood clots in 2011-2012
o Key patent expirations 2027-2029
o Already have provisional generics approvals
o Approved for cancer in 2014
o Key patent expiration in 2028
o Predicted income in 2028 of $33.7 bn
o Approved for cancer in 2014
o Key patent expiration in 2028
o Predicted income in 2026 of $11.75 bn
o Approved for multiple sclerosis in 2017
o Key patent expirations 2028-2029
o There is already competition to create and launch a biosimilar
Meeting the challenge of the patent cliff
Patent protection and exclusivity allows drug developers to protect themselves from generic and biosimilar competition, permitting them to get a return on investment and reinvest money into R&D, as well as providing payback for their investors. To increase their protection and therefore maintain their market share, there are a number of approaches that originator companies can take.
Companies need to start planning long before patent and exclusivity expiration, by carrying out an analysis of the expected impact of generic competition. Creating a dense network of overlapping patents around the therapeutic, known as a patent thicket, makes it much harder for a competitor to develop a generic form. These, however, can impact innovation and thereby slow research and development of other originator products. [10]
The product lifecycle can be extended by creating new formulations and delivery systems, for example improving safety and efficacy, changing from multiple doses per day to daily, weekly or less frequent, or moving from injected to oral or transdermal delivery. Finding new indications for therapeutics allows companies to gain new patents or exclusivity periods, as well as increasing the population that can take the drug. [5]
Companies can maintain their market share by creating brand loyalty programs, including patient support systems and discounts for patients or healthcare providers. They can also capture part of the generics market themselves by selling authorised generics through a third party, or by collaborating with a generics manufacturer. [5]
Forward planning also includes maintaining pipelines so that new drugs or lifecycle extensions are approaching approval as older ones are reaching the end of their patent and exclusivity period. This can be supported by licensing in mid- and late-stage products and collaborating with preclinical- and clinical-stage companies.
References
1. Holston, P.L. and J. DeRuiter, Drug Patent Expirations and the “Patent Cliff”. U.S. Pharm., 2012(6 Generic suppl): p. 12-20.
2. Sagonowsky, E., The decade's top 10 patent losses, worth a whopping $915B in lifetime sales. 17 August 2014. Available from: https://www.fiercepharma.com/pharma/decade-s-top-10-patent-losses-featuring-seismic-sales-shifts.
3. Manalac, T., 5 Pharma Powerhouses Facing Massive Patent Cliffs—And What They’re Doing About It. BioSpace, 19 February 2025. Available from: https://www.biospace.com/business/5-pharma-powerhouses-facing-massive-patent-cliffs-and-what-theyre-doing-about-it.
4. Frequently Asked Questions on Patents and Exclusivity. US Food and Drug Administration. Last accessed: 26 March 2025. Available from: https://www.fda.gov/drugs/development-approval-process-drugs/frequently-asked-questions-patents-and-exclusivity.
5. Top Strategies for Pharma Profitability after Drug Patents Expire. DrugPatentWatch. Last accessed: 8 March 2025. Available from: https://www.drugpatentwatch.com/blog/top-strategies-for-pharma-profitability-after-drug-patents-expire/.
6. Corona, A., Key drugs losing patent protection in 2025. Pharma Manufacturing, 12 December 2024. Available from: https://www.pharmamanufacturing.com/home/article/55249347/key-drugs-losing-patent-protection-in-2025.
7. Burke, H., Top 10 drugs with patents due to expire in the next five years. Proclinical, 16 February 2024. Available from: https://www.proclinical.com/blogs/2024-2/top-10-drugs-with-patents-due-to-expire-in-the-next-5-years.
8. Riyaz, S. The Trajenta Patent Thicket: Patents expiring in 2025. Last accessed: 27 March 2025. Available from: https://www.greyb.com/blog/trajenta-patent-expiration/.
9. Lee, G., The Battle for Billions: Understanding the Ozempic Patent Landscape. Science and Technology Law Review, 26 November 2024. Available from: https://journals.library.columbia.edu/index.php/stlr/blog/view/653.
10. Untangling Patent Thickets: The Hidden Barriers Stifling Innovation. TT Consultants. Last accessed: 28 June 2024. Available from: https://ttconsultants.com/untangling-patent-thickets-the-hidden-barriers-stifling-innovation/.
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