Potential losses exceed $300 billion! Nearly 200 drugs are facing a patent cliff

The pharmaceutical industry is set to face a wave of patent expirations.

At the beginning of this year, Dr. Joanna Sadowska posted a “Pharma Patent Cliff” chart on LinkedIn. She pointed out that in the coming years, nearly 200 drugs will lose their patent protection, including at least 69 blockbuster drugs with annual sales exceeding $1 billion each. The cumulative loss in sales is expected to exceed $300 billion.

To this end, DrugTimes has compiled the patent information for some of the blockbuster drugs. By 2037, more than 25 products will face the patent cliff. Based on the sales in 2024, the combined potential loss in revenue is expected to exceed $236.4 billion.

Among them, there are a total of 9 drugs worth tens of billions of dollars, including Pfizer’s apixaban, Merck’s Keytruda, BMS’s Opdivo, Johnson & Johnson’s daratumumab, Sanofi’s dupilumab, Novo Nordisk’s semaglutide, AbbVie’s risankizumab, Eli Lilly’s tirzepatide, and Vertex’s Trikafta.

For pharmaceutical companies, Merck may face the greatest potential losses, but having the greatest potential losses does not necessarily mean that the company is at the highest risk. In July 2024, a report released by Morgan Stanley showed that by 2030, Amgen (67%), BMS (63%), and Merck (56%) will face the highest revenue risks.

Conversely, Vertex (6%), Gilead (24%), AbbVie (29%), Eli Lilly (31%), and Pfizer (33%) have lower risk assessments.

Table of Contents

• Amgen
• BMS
• Merck
• Other Pharmaceutical Companies
• Summary

Amgen

In this list of patent cliff risks, Amgen faces the highest revenue risk. The main reason is that four core products—denosumab (Prolia), denosumab (Xgeva), etanercept (Enbrel), and apremilast (Otezla)—will lose their exclusive rights simultaneously. These four products had a combined sales of $12.041 billion in 2024, accounting for about one-third of Amgen’s total annual revenue.

Secondly, Amgen’s GLP-1 drug, Marifide, is venturing into a highly competitive market; the Phase II clinical failure of the systemic sclerosis treatment drug Fipaxalparant cannot be ignored due to its research and development uncertainties; by the end of 2024, the company’s total debt was $60.1 billion, with a leverage ratio of 4.5 times, indicating significant debt pressure.

In the face of these risks, Amgen had anticipated and proactively acquired Horizon to navigate through the challenging period brought about by the patent cliff. Currently, Tepezza (teprotumumab), Krystexxa (pegloticase), and Uplizna (inebilizumab) acquired from Horizon are rapidly gaining market share.

Among them, Uplizna is expected to achieve two important milestones this year, including the approval of indications for IgG4-related diseases and the submission for myasthenia gravis indications in the United States.

BMS

As the second on the list, BMS is primarily facing the crisis of the decline of two “cash cows”—apixaban and Opdivo. According to BMS’s 2024 financial report, the combined sales of these two products reached $23.4 billion, accounting for about half of the company’s total revenue.

Apixaban not only faces the upcoming generic competition but also the “test” of the U.S. Medicare Part D reform in its final sprint, which will affect its continued market expansion in 2025. According to Evaluate Pharma’s forecast, BMS will lose over $10 billion due to apixaban by 2023.

Facing the patent cliff challenge, BMS has strategically adopted a successful optimization model to improve profitability through organizational streamlining and operational efficiency. Specifically, after announcing a $1.5 billion cost-cutting plan in April 2024, BMS set a new target of $2 billion in cost reductions in February 2025.

To achieve this goal, BMS has terminated several pipelines, including Cendakimab and the second-generation TYK2 inhibitor BMS-986322, along with corresponding layoffs.

Recommended Reading: $2 Billion! BMS Unveils a “Cost-Saving Strategy” to Overcome the Patent Cliff!

Short-term pain is necessary to build momentum for long-term growth. At the end of 2023, BMS acquired Karuna for $14 billion, gaining its core pipeline drug Cobenfly. Although the drug’s sales of $10 million in its first full quarter after launch last year are not significant, it is a promising start.

BMS’s CEO Boerner said, “We plan to initiate seven Phase III clinical trials for Cobenfly in 2025 to expand its use among patients.” This shows that BMS has shifted its focus towards the field of neuroscience.

In addition, BMS’s fastest-growing products in terms of sales are the cardiac myosin inhibitor Camzyos and the CD19 CAR-T therapy Breyanzi, which are expected to become the core of the company’s growth over the next five years.

Merck

Under normal circumstances, the protection period for drug patents is 20 years. However, considering the long development cycle of innovative drugs, which involves molecular screening, pharmaceutical research, Phase I-III clinical trials, and marketing applications before approval, the actual protection period is only about 10 years.

This 10-year cycle represents a generational shift in the field of innovative drugs. After 10 years, BMS and Merck, which were the first to lead in the PD-1 era, will both face challenges due to the patent cliff. This is a classic example of the saying, “The development of things is a spiral ascent.”

During these ten years, the OK battle began. Initially, Keytruda achieved a turnaround with “first-line treatment for non-small cell lung cancer,” and eventually topped the list of drugs with 40 indications. Merck’s cultivation of Keytruda has been relentless. The most direct manifestation is the sheer number of Keytruda’s clinical registrations. According to ClinicalTrials, Keytruda has over 1,400 registrations, an unprecedented scale.

However, in the next five years, Keytruda, sitagliptin/metformin, and letermovir, among other blockbuster drugs, will face the patent cliff. Choosing the right successor products is crucial for Merck. Based on the BD transaction amounts over the past two years, Merck has partnered with Kolumbo and Daiichi Sankyo for a total of $33.8 billion, heavily investing in the ADC field.

Everyone knows what Sima Zhao is thinking. To prolong the life of Keytruda, it will continue to heavily invest in combination therapies. In the future, Keytruda will be Keytruda, and PD-1 will be PD-1.

It is worth noting that Merck’s other core revenue pillar, the HPV vaccine Gardasil 9, has not met revenue expectations, mainly due to the impact of the Chinese market. Shipments were suspended in February this year to accelerate inventory reduction, with an expected return to growth in the second half of 2025.

Other Pharmaceutical Companies

Pfizer’s oncology drugs Ibrance, Xtandi, Inlyta, the transthyretin amyloid cardiomyopathy drug Vyndaqel series, and the arthritis drug Xeljanz will all face patent expiration before 2027;

Johnson & Johnson’s oncology drugs Darzalex, Erleada, the pulmonary arterial hypertension drugs Opsumit, Uptravi, the anti-angiogenic drug Xarelto, and the HIV drug Edurant will face patent expiration before 2030;

Eli Lilly’s diabetes drugs Trulicity, Jardiance, the arthritis drug Taltz, and the oncology drug Cyramza will face patent expiration in 2030.

Life is like morning dew; the days gone by are full of bitterness. Faced with the patent cliff, multinational pharmaceutical companies are meeting the challenge by strengthening research and development, expanding markets, and optimizing product portfolios.

Summary

The “patent cliff” phenomenon in the pharmaceutical industry vividly illustrates the dialectical law of market competition. When the market exclusivity of originator drugs ends, biosimilars and generics flood the market. This seemingly catastrophic event for pharmaceutical companies is actually a boon for the general public—safe and reliable low-cost alternative drugs significantly reduce medical expenses.

However, this widespread benefit always comes late, far behind the era of windfall profits that created the patent cliff. Faced with generic competition, originator drug companies can still maintain profitability by adjusting production and pricing.

More significantly, these pharmaceutical giants often prepare in advance by shifting their research and development focus to breakthrough new drugs, rebuilding their profit peaks on the high ground of innovation, and waiting for the next patent cycle to come around.

This cyclical industry pattern is akin to the law of nature: it involves the determination of cutting off one’s own arm to save the rest of the body, yet it also contains the rebirth of the phoenix. In the dynamic balance between commercial interests and public welfare, it continues to drive the progress of human pharmaceutical endeavors.

【Editor’s note】The above content (~8000 words) is a quick translation of a Chinese article (posted on 2025-2-18) by DrugTimes team. To read the original article, please click here. All comments are warmly welcome. Many thanks!