2025 U.S. Patent Cliff Alert: Top 10 Blockbuster Drugs Face Loss of Market Exclusivity

In the pharmaceutical industry, blockbuster drugs lose patent protection every year, but the list for 2025 is particularly noteworthy. This year, several major drugs, including Johnson & Johnson's Stelara, Regeneron's Eylea, Amgen's Prolia/Xgeva, and Novartis' Entresto, will face the loss of exclusivity in the U.S. market. With significant sales at stake, the competition in the market is expected to intensify after their exclusivity ends.

According to the latest report by Fierce Pharma, the following are the top ten drugs that will lose exclusivity in the U.S. market in 2025.

 Stelara (Johnson & Johnson)

Indications: Psoriatic Arthritis, Plaque Psoriasis, Crohn's Disease, Ulcerative Colitis

U.S. Sales in 2024: $6.72 Billion

Stelara, Johnson & Johnson's heavyweight immunology drug, achieved global sales of $10.36 billion in 2024. However, with the approaching patent cliff, Stelara is facing fierce competition from biosimilars. In January 2025, Amgen's Wezlana, the first Stelara biosimilar, was launched in the United States. Subsequently, multiple biosimilars from companies such as Teva Pharmaceuticals, Alvotech, Sandoz, Samsung Bioepis, and Biocon Biologics were also approved and are planned for release in 2025. Despite Johnson & Johnson extending some patent protection through legal settlements, intensified competition caused Stelara’s international sales to drop by 33% year-over-year in Q4 2024, with global sales declining by 14.7% year-over-year. Johnson & Johnson anticipates achieving 3% annual growth in 2025 despite biosimilar competition.

 Eylea (Regeneron)

Indications: Wet age-related macular degeneration, diabetic macular edema, retinal vein occlusion, retinopathy of prematurity, diabetic retinopathy

U.S. Sales in 2024: $4.77 Billion

Eylea, a blockbuster ophthalmology drug from Regeneron, generated $4.77 billion in sales in the U.S. in 2024. However, its sales growth has stagnated since Roche's Vabysmo entered the market in 2022. In November 2024, Amgen's Pavblu, the first biosimilar to Eylea, launched in the U.S., further intensifying market competition. Regeneron also faces biosimilar competition from companies such as Biocon, Biogen, and Samsung Bioepis. Additionally, Regeneron's long-acting version, Eylea HD, underperformed, with its Q4 2024 sales dropping to $305 million from $392 million in Q3. Regeneron aims to enhance the market performance of Eylea HD to address future competition.

 Prolia/Xgeva (Amgen)

Indications: For the treatment of osteoporosis with high fracture risk, bone loss in patients receiving hormone ablation therapy for prostate or breast cancer; prevention of skeletal-related events in patients with bone metastases from cancer, giant cell tumor of bone, and hypercalcemia caused by malignant tumors.

U.S. Sales in 2024: $4.39 Billion

Prolia and Xgeva, two key bone drugs from Amgen, had total sales of $4.39 billion in the U.S. in 2024. The main patents for these two drugs expired in February 2025. In March 2024, Sandoz's Jubbonti and Wyost became the first FDA-approved biosimilars to Prolia/Xgeva, with plans to launch in the U.S. on May 31, 2025. Additionally, Celltrion’s biosimilar received FDA approval in January 2025 and is expected to be launched on June 1. Amgen is still engaged in patent litigation with companies such as Samsung Bioepis, Fresenius Kabi, and Accord BioPharma.

 Entresto (Novartis)

Indications: Heart Failure

U.S. Sales in 2024: $4.05 Billion

Entresto, a heart failure treatment drug under Novartis, achieved sales of $4.05 billion in the U.S. in 2024. However, with the expiration of its key combination patent in July 2025, Entresto may lose its market exclusivity in the U.S. by mid-2025. Novartis has filed lawsuits against multiple generic drug companies in an attempt to block the launch of generic versions of Entresto. Despite this, several companies, including Torrent, Dr. Reddy’s Laboratories, Zydus, MSN, Alkem, and Lupin, have received FDA approval to produce generic versions of Entresto. In January 2025, the U.S. Court of Appeals for the Federal Circuit ordered MSN to delay the launch of its generic version of Entresto pending further rulings on Novartis' patent protection. Additionally, Entresto is among the first drugs to undergo Medicare price negotiations under the Inflation Reduction Act.

 Soliris (AstraZeneca)

Indications: Paroxysmal Nocturnal Hemoglobinuria, Atypical Hemolytic Uremic Syndrome, Generalized Myasthenia Gravis, Neuromyelitis Optica Spectrum Disorders

U.S. Sales in 2024: $1.52 Billion

Soliris, a rare disease drug under AstraZeneca, generated $1.52 billion in sales in the U.S. in 2024. Since its approval in 2007, the drug has enjoyed nearly two decades of market exclusivity. However, with the looming threat of biosimilars, Soliris' sales have started to decline. AstraZeneca has responded to the market downturn of Soliris by promoting its follow-up drug Ultomiris. In 2024, Ultomiris achieved global sales of $3.9 billion, surpassing Soliris' $2.59 billion. Amgen's Soliris biosimilar Bkemv has received FDA approval and is planned for launch in the U.S. in the second quarter of 2025. Additionally, Samsung Bioepis' Epysqli has also been approved by the FDA and is set to be commercialized in the U.S. by Teva.

 Promacta (Novartis)

Indications: Thrombocytopenia, Aplastic Anemia

U.S. Sales in 2024: $1.18 Billion

Promacta, a thrombocytopenia treatment drug under Novartis, achieved sales of $1.18 billion in the U.S. in 2024. The drug's patent protection expired in 2024, and it is expected to face generic competition by mid-2025. In April 2024, Annora’s generic version of Promacta was approved for the first time and granted a 180-day exclusive sales period. In January this year, Hetero's generic version was also approved.

 Simponi/Simponi Aria (Johnson & Johnson)

Indications: Rheumatoid arthritis, Psoriatic arthritis, Ankylosing spondylitis, Ulcerative colitis, Polyarticular juvenile idiopathic arthritis

U.S. Sales in 2024: $1.08 Billion

Over the past decade, Simponi has been a blockbuster drug for Johnson & Johnson, reaching a peak of nearly $2.28 billion in global sales in 2021. Its substance patent is set to expire in 2024, and the first biosimilar, AVT05 (developed by Teva and Alvotech), is expected to receive FDA approval and launch in the fourth quarter of 2025. Additionally, Bio-Thera Solutions is also developing a Simponi biosimilar, BAT2506, and has reached a U.S. market authorization agreement with Accord BioPharma.

 Tysabri (Biogen)

Indications: Multiple Sclerosis, Crohn's Disease

U.S. Sales in 2024: $920 Million

Tysabri, a multiple sclerosis treatment drug under Biogen, generated $9.2 billion in sales in the U.S. in 2024. In 2023, Sandoz's Tysabri biosimilar Tyruko received FDA approval, but its U.S. launch was postponed to 2025 due to the need for approval of the JCV antibody test. Nevertheless, Tyruko has already been launched in the UK and Germany. Biogen uses the STRATIFY test, developed in collaboration with Quest Diagnostics, to assess the risk of patients using Tysabri.

 Tasigna (Novartis)

Indications: Chronic Myeloid Leukemia

2024 U.S. Sales: $848 Million

Tasigna's substance patent has expired in the United States and Europe, and Novartis anticipates that its generic versions will enter the U.S. market by mid-2025. Generic drugs from companies such as Apotex, MSN Laboratories, and Hetero Labs have received tentative FDA approval. Additionally, Azurity Pharmaceuticals' newly formulated drug, Danziten, has been approved and does not require fasting, adding competitive pressure to Tasigna.

 Brilinta (AstraZeneca)

Indications: Acute Coronary Syndrome, Coronary Heart Disease, Acute Ischemic Stroke, or High-Risk Transient Ischemic Attack

U.S. Sales in 2024: $751 Million

Brilinta, an antiplatelet drug under AstraZeneca, recorded sales of $751 million in the U.S. in 2024. Despite high expectations, its performance fell short due to clinical trial failures and increased market competition. In 2025, Brilinta is expected to face competition from generic drugs. Companies such as Sandoz, Dr. Reddy’s Laboratories, and Torrent Pharmaceuticals have received tentative FDA approval for generic versions of Brilinta.

In 2025, the wave of patent expirations in the U.S. market will have a profound impact on the pharmaceutical industry. The expiration of market exclusivity for these blockbuster drugs will not only lead to price competition but may also reshape the market landscape. Pharmaceutical companies need to strategize in advance by developing new drugs, expanding markets, or promoting follow-up drugs to address the challenges. For investors and patients, this also means more choices and lower medication costs.

In the future market competition, who will stand out, and who will face difficulties? Let's wait and see!