Top 10 Drugs Losing US Exclusivity in 2025
Summary
1. Stelara: 2024 U.S. sales: $6.72 billion2. Eylea: 2024 U.S. sales: $4.77 billion
3. Prolia/Xgeva: 2024 U.S. sales: $4.39 billion
4. Entresto: 2024 U.S. sales: $4.05 billion
5. Soliris: 2024 U.S. sales: $1.52 billion
6. Promacta: 2024 U.S. sales: $1.18 billion
7. Simponi/Simponi Aria: 2024 U.S. sales: $1.08 billion
8. Tysabri: 2024 U.S. sales: $920 million
9. Tasigna: 2024 U.S. sales: $848 million
10. Brilinta: 2024 U.S. sales: $751 million
Introduction
While the pharmaceutical industry routinely faces high-profile losses of exclusivity each year, this year's list is particularly notable.
Johnson & Johnson’s Stelara is already contending with several biosimilars, with more expected throughout the year. With $6.72 billion in U.S. sales projected for 2024, Stelara represents the largest U.S. loss of exclusivity since AbbVie’s Humira patent cliff in early 2023. Although Johnson & Johnson had anticipated a “late 2023” patent expiration, the company extended Stelara’s market life through legal settlements (1, 2, 3).
Johnson & Johnson is not alone in losing exclusivity on key revenue drivers this year. Regeneron faces biosimilar competition for its eye drug Eylea, Amgen for its bone medicines Prolia and Xgeva, and Novartis for its heart failure therapy Entresto.
Eylea encountered its first U.S. biosimilar when Amgen launched Pavblu in November 2024. Despite the biosimilar launch occurring last year, Eylea remains relevant for this report due to ongoing market developments for Regeneron (2).
Company: Johnson & Johnson
2024 U.S. sales: $6.72 billion
Diseases: Wet age-related macular degeneration, diabetic macular edema, retinal vein occlusion, retinopathy of prematurity, diabetic retinopathy
Company: Regeneron
2024 U.S. sales: $4.77 billion
Eylea’s trajectory has diverged from the typical megablockbuster story. Even before the loss of patent protection, Eylea’s sales plateaued due to competition from Roche’s Vabysmo, which entered the market in early 2022 and quickly gained ground. From 2021 to 2024, Eylea’s global sales remained steady, ranging between $9.2 billion and $9.6 billion annually, while Vabysmo’s 2024 sales surpassed $4 billion, echoing Eylea’s own rapid ascent a decade earlier.
The competitive landscape intensified in November 2024, when Amgen launched Pavblu, the first Eylea biosimilar in the U.S., generating $31 million in its initial nine weeks. This launch followed a West Virginia judge’s decision favoring Amgen, after previously blocking launches from Biocon’s Yesafili and Biogen/Samsung Bioepis’ Opuviz—both of which remain barred from the U.S. market until 2027 despite FDA approvals.
Regeneron continues to defend its franchise on multiple fronts. The company is engaged in legal and regulatory battles with Formycon over the FDA-approved biosimilar Ahzantive and with Celltrion over Eydenzelt, approved in Europe but not yet in the U.S. Additionally, Regeneron has filed a patent infringement suit against Sandoz, whose biosimilar Enzeevu has also received FDA approval.
Compounding these challenges, Regeneron’s longer-acting follow-up, Eylea HD, has struggled to gain traction. Sales dropped from $392 million in the third quarter of 2024 to $305 million in the fourth quarter. With Vabysmo expected to maintain market exclusivity until 2039, Regeneron’s best hope for the Eylea franchise is to strengthen Eylea HD’s competitive profile.
Despite these headwinds, the aging global population and advances in diagnostic imaging continue to expand the overall market for retinal disease treatments.
Johnson & Johnson’s Stelara is already contending with several biosimilars, with more expected throughout the year. With $6.72 billion in U.S. sales projected for 2024, Stelara represents the largest U.S. loss of exclusivity since AbbVie’s Humira patent cliff in early 2023. Although Johnson & Johnson had anticipated a “late 2023” patent expiration, the company extended Stelara’s market life through legal settlements (1, 2, 3).
Johnson & Johnson is not alone in losing exclusivity on key revenue drivers this year. Regeneron faces biosimilar competition for its eye drug Eylea, Amgen for its bone medicines Prolia and Xgeva, and Novartis for its heart failure therapy Entresto.
Eylea encountered its first U.S. biosimilar when Amgen launched Pavblu in November 2024. Despite the biosimilar launch occurring last year, Eylea remains relevant for this report due to ongoing market developments for Regeneron (2).
Amgen generated $4.39 billion in revenue from Prolia and Xgeva in 2024. The company, known for its biosimilar portfolio, will now face competition as biosimilars begin to erode the market share of these originators starting in late May and early June (2).
Novartis has warned of a “mid-2025” loss of U.S. exclusivity for Entresto, as a key patent expires this summer. Novartis also has two other major products on this list: Promacta and Tasigna.Further down the list, AstraZeneca has two high-profile drugs nearing patent expiration. Soliris, acquired through AZ’s purchase of Alexion, is expected to face its first biosimilar from Amgen in the second quarter of 2025. Brilinta, a cardiometabolic drug once projected as a blockbuster but which underperformed expectations, is also losing U.S. patent protection soon (2).
To illustrate the prominence of drugs on this list, last year’s leader was Bristol Myers Squibb’s Sprycel, with $1.45 billion in prior-year U.S. sales. However, compared to the 2025 patent expirations, Sprycel would rank only sixth.This year’s wave of biosimilar launches and patent expirations marks a significant shift in the pharmaceutical landscape, with major implications for market dynamics, pricing, and patient access. Johnson & Johnson and other top pharma players will need to navigate these challenges while leveraging newer therapies to sustain growth13.
1. Stelara
Diseases: Psoriatic arthritis, plaque psoriasis, Crohn’s disease, ulcerative colitisCompany: Johnson & Johnson
2024 U.S. sales: $6.72 billion
Johnson & Johnson’s immunology blockbuster first appeared on the loss-of-exclusivity radar in 2023, as key patents were set to expire that fall. However, J&J managed to delay biosimilar competition in the U.S. by reaching settlements with several biosimilar developers, postponing their product launches until this year (1).
Now, the U.S. market is seeing a surge of Stelara biosimilars. Amgen’s Wezlana, approved in late 2023, was the first to launch on January 1, 2025, following a legal agreement that delayed its entry in exchange for resolving patent litigation. Since then, at least six more Stelara biosimilars have received FDA approval and are planning 2025 launches, including Alvotech and Teva’s Selarsdi, Sandoz and Samsung Bioepis’ Pyzchiva, Biocon’s Yesintek, and Celltrion’s Steqeyma. Fresenius Kabi and Formycon’s Otulfi, along with Accord’s Imuldosa, are also expected to enter the market in the first half of the year23.
Many of these biosimilars have already launched in Europe, where Stelara’s exclusivity ended in July 2024. The influx of competition has had a significant impact on sales: J&J reported a nearly 33% year-over-year decline in international Stelara sales in its first full quarter facing biosimilar rivals, while U.S. sales dropped 5% in the fourth quarter of 2024. Globally, Stelara’s annual sales fell 4.6% to $10.4 billion1.
Despite these headwinds, J&J remains optimistic. CEO Joaquin Duato stated in January that the company expects to achieve 3% annual growth in 2025, only a slight decrease from the previous year’s 4.3% growth, by offsetting Stelara losses with new product launches and portfolio management1.
J&J is also looking to recoup lost Stelara revenue by transitioning patients to its newer immunology therapy, Tremfya. This strategy mirrors AbbVie’s approach after Humira’s patent loss, where the company successfully shifted patients to Skyrizi and Rinvoq. Tremfya, already approved for psoriatic arthritis, plaque psoriasis, and ulcerative colitis, received FDA approval for Crohn’s disease in March 2025, aligning its indications with Stelara’s and strengthening J&J’s succession plan for its immunology franchise4.
In summary, Stelara’s loss of exclusivity in 2025 marks a major shift in the U.S. immunology market, with multiple biosimilars entering the field and J&J executing a strategic transition to maintain its leadership in autoimmune therapies214.
2. Eylea
Company: Regeneron
2024 U.S. sales: $4.77 billion
Eylea’s trajectory has diverged from the typical megablockbuster story. Even before the loss of patent protection, Eylea’s sales plateaued due to competition from Roche’s Vabysmo, which entered the market in early 2022 and quickly gained ground. From 2021 to 2024, Eylea’s global sales remained steady, ranging between $9.2 billion and $9.6 billion annually, while Vabysmo’s 2024 sales surpassed $4 billion, echoing Eylea’s own rapid ascent a decade earlier.
The competitive landscape intensified in November 2024, when Amgen launched Pavblu, the first Eylea biosimilar in the U.S., generating $31 million in its initial nine weeks. This launch followed a West Virginia judge’s decision favoring Amgen, after previously blocking launches from Biocon’s Yesafili and Biogen/Samsung Bioepis’ Opuviz—both of which remain barred from the U.S. market until 2027 despite FDA approvals.
Regeneron continues to defend its franchise on multiple fronts. The company is engaged in legal and regulatory battles with Formycon over the FDA-approved biosimilar Ahzantive and with Celltrion over Eydenzelt, approved in Europe but not yet in the U.S. Additionally, Regeneron has filed a patent infringement suit against Sandoz, whose biosimilar Enzeevu has also received FDA approval.
Compounding these challenges, Regeneron’s longer-acting follow-up, Eylea HD, has struggled to gain traction. Sales dropped from $392 million in the third quarter of 2024 to $305 million in the fourth quarter. With Vabysmo expected to maintain market exclusivity until 2039, Regeneron’s best hope for the Eylea franchise is to strengthen Eylea HD’s competitive profile.
Despite these headwinds, the aging global population and advances in diagnostic imaging continue to expand the overall market for retinal disease treatments.
3. Prolia/Xgeva
Diseases: Osteoporosis at high risk of fracture; bone loss in patients with prostate or breast cancer undergoing hormone ablation therapy; prevention of skeletal-related events in patients with bone metastases from cancer; giant cell tumor of the bone; hypercalcemia of malignancy
Company: Amgen
2024 U.S. sales: $4.39 billion
Amgen’s Prolia and Xgeva, which share the active ingredient denosumab, have enjoyed a strong market presence since their launch in 2010. Together, they reached blockbuster status early, with combined global sales of $1.22 billion in 2012.
By 2024, both drugs continued to grow globally: Prolia’s sales rose 8% year-over-year to $4.37 billion, while Xgeva increased 5% to $2.23 billion. In the U.S., Prolia and Xgeva generated $4.39 billion combined, with Prolia’s sales up 6% and Xgeva’s down 1%. Prolia was Amgen’s top-selling drug in 2024, with Xgeva ranking third.
The two drugs serve different indications and dosing schedules. Prolia primarily treats osteoporosis in men and postmenopausal women at high fracture risk, while Xgeva is used to prevent skeletal-related events in cancer patients with bone metastases. Denosumab works by binding to RANKL, blocking its interaction with the receptor RANK, thereby inhibiting osteoclast-mediated bone resorption.
The key RANKL antibody patent protecting Prolia and Xgeva expired on February 19, 2025.
Sandoz was the first to receive FDA approval for interchangeable biosimilars referencing Prolia and Xgeva, launching Jubbonti and Wyost in March 2024. However, as is typical with major blockbusters, Amgen initiated patent litigation against Sandoz in March 2023, asserting infringement of 21 patents expiring as late as 2037. The companies settled in March 2024, with Sandoz agreeing to launch its biosimilars in the U.S. no earlier than May 31, 2025, or sooner under certain conditions tied to market competition.
In January 2025, Amgen also settled with Celltrion, permitting the Korean company to launch its denosumab biosimilars in the U.S. as early as June 1, 2025. Celltrion announced FDA approval for these biosimilars earlier that month.
Amgen continues to pursue legal action against Samsung Bioepis, Fresenius Kabi, and Accord BioPharma, with their cases consolidated for coordinated pretrial proceedings in New Jersey federal court.
Meanwhile, Shanghai Henlius Biotech and partner Organon had their biosimilar HLX14 accepted for FDA review in October 2024. Amneal, partnered with Fresenius Kabi’s mAbxience, also submitted two denosumab biosimilars for FDA review recently.
Despite the impending biosimilar competition, Prolia and Xgeva remain significant contributors to Amgen’s portfolio. In the first quarter of 2025, Xgeva sales increased 1% year-over-year to $566 million, though Amgen expects sales erosion later in the year due to biosimilars. Prolia’s first-quarter sales rose 10% to $1.1 billion, driven by volume growth offsetting pricing pressures.
Overall, Amgen’s strategic settlements and ongoing legal efforts aim to manage biosimilar competition while maintaining strong sales momentum for Prolia and Xgeva in a changing market landscape.
Company: Novartis
2024 U.S. sales: $4.05 billion
Novartis is preparing for the potential entry of generic versions of Entresto in the U.S. this year, while vigorously defending its blockbuster heart failure drug. Entresto, approved by the FDA in 2015 for heart failure treatment, faces a key patent expiration in July 2025. This patent, covering the sacubitril-valsartan combination, is central to Novartis’ market exclusivity, which the company forecasts will end in mid-2025, subject to ongoing patent and regulatory litigation.
Multiple generic manufacturers—including Torrent, Dr. Reddy’s, Zydus, MSN, Alkem, and Lupin—have secured FDA approvals for their Entresto biosimilars or generics. Since 2020, Novartis has actively pursued legal action against several of these companies, resulting in confidential settlements and mixed legal outcomes.
A focal point of recent patent disputes involves MSN Pharmaceuticals, which received FDA approval for its Entresto generic in July 2024. Novartis responded by suing the FDA, alleging that the approval led to labeling that “inappropriately rewrites Entresto’s approved indication.” The FDA rejected Novartis’ Citizen Petition to block other generics, and a federal judge upheld MSN’s approval in October 2024.
Novartis also sought to block MSN’s generic launch through injunctions, but a Delaware judge denied the request in August 2024. Although Novartis appealed, it again lost in federal court in December. However, in January 2025, the U.S. Court of Appeals for the Federal Circuit ordered MSN to delay its launch “until further notice” while the court reviews Novartis’ efforts to extend patent protection.
In a significant January 2025 ruling, the Federal Circuit upheld the validity of Novartis’ key Entresto patent, reversing an earlier district court decision that had invalidated it. Novartis plans to enforce this patent through its pediatric exclusivity period, which expires in July 2025.
Entresto remains Novartis’ top-selling drug, generating approximately $7.8 billion in net sales in 2024. Beyond patent challenges, the drug is among the first subject to Medicare price negotiations under the Inflation Reduction Act, effective in early 2026. Novartis CEO Vas Narasimhan has expressed confidence that the company can manage the impact of these price reductions, noting that the affected drugs are nearing patent expiration and companies have been preparing alternative revenue streams.
Overall, while Novartis faces mounting generic competition and pricing pressures, the company continues to leverage legal strategies and patent protections to defend Entresto’s market position through mid-2025 and beyond.
Company: AstraZeneca
2024 U.S. sales: $1.52 billion
AstraZeneca’s Soliris has enjoyed nearly two decades of market exclusivity since its 2007 FDA approval for paroxysmal nocturnal hemoglobinuria (PNH). Now, as biosimilar competition looms, AstraZeneca is leveraging its follow-up drug, Ultomiris, to sustain its leadership in rare complement-mediated diseases.
AstraZeneca acquired Soliris through its $39 billion purchase of Alexion Pharmaceuticals in 2021. Since then, Soliris has remained a significant revenue driver, though sales have declined recently as the company has shifted focus to Ultomiris. Approved in 2018 for the same indications, Ultomiris benefits from a longer patent life, with exclusivity extending to 2035. In 2024, Ultomiris surpassed Soliris in global sales, generating $3.9 billion compared to Soliris’ $2.59 billion. AstraZeneca attributes Soliris’ 18% worldwide sales decline to the “successful conversion” of patients to Ultomiris.
Alongside Soliris and Ultomiris, AstraZeneca markets Voydeya, a recently approved add-on therapy, aiming to maintain dominance in the PNH market despite challenges from Novartis’ oral PNH drug Fabhalta and Apellis’ C3 inhibitor Empaveli. Biosimilars have already impacted Soliris sales in Europe, but the U.S. market will face its first biosimilar launches this year.
Amgen’s Soliris biosimilar, Bkemv (eculizumab-aeeb), received FDA approval in May 2024 as the first interchangeable biosimilar for PNH and aHUS. The interchangeable designation allows pharmacy-level substitution without prescriber approval. Under a 2020 settlement with Alexion, Amgen is set to launch Bkemv in the U.S. in the second quarter of 2025. The FDA has confirmed that Bkemv is “highly similar with no clinically meaningful differences” from Soliris and carries the same boxed warning and Risk Evaluation and Mitigation Strategy (REMS) due to the risk of serious meningococcal infections.
Samsung Bioepis’ Epysqli (eculizumab-aagh), the second FDA-approved Soliris biosimilar, gained approval in July 2024 for PNH, aHUS, and later expanded indications to include generalized myasthenia gravis. In January 2025, Teva Pharmaceuticals entered a licensing and commercialization agreement with Samsung Bioepis to market Epysqli in the U.S., while Samsung handles development, manufacturing, and supply. Epysqli is offered at a 30% discount to Soliris’ wholesale acquisition cost and is already marketed in Europe. The FDA has provisionally designated Epysqli as interchangeable once Amgen’s exclusivity expires.
The U.S. launch of Epysqli was announced in April 2025, marking a significant expansion of biosimilar options for patients with rare complement-mediated disorders. Both Bkemv and Epysqli carry the same safety profiles and are subject to REMS programs to mitigate serious infection risks.
AstraZeneca’s strategic transition from Soliris to Ultomiris, combined with the introduction of biosimilars, reflects the evolving competitive landscape in rare disease treatment. While Soliris faces biosimilar erosion, Ultomiris and Voydeya position AstraZeneca to maintain a strong presence in this specialized market.
Company: Novartis
2024 U.S. sales: $1.18 billion
While much attention surrounds Novartis’ impending loss of exclusivity for its heart failure drug Entresto, two other blockbusters—Promacta and Tasigna—are also set to face generic competition in the U.S. in 2025. For forecasting, Novartis projects all three drugs will lose U.S. market exclusivity by mid-2025, subject to ongoing patent and regulatory developments.
Promacta, originally developed by Ligand and GSK and acquired by Novartis in 2014 as part of a $16 billion oncology portfolio purchase, has steadily grown since its 2008 FDA approval. The drug, known as Revolade in Europe, expanded its label to include first-line aplastic anemia in 2018, the year it first achieved blockbuster status. In 2024, Promacta generated $2.2 billion globally, with $1.2 billion from the U.S., marking a 2% decline attributed by Novartis to reduced proactive promotion.
Promacta is a daily oral therapy for thrombocytopenia and competes primarily with Amgen’s Nplate, a once-weekly injection approved in 2008 for chronic immune thrombocytopenia. Nplate’s 2024 sales reached $1.46 billion, down 1% from the prior year. Other competitors include Sobi’s Doptelet and Rigel Pharmaceuticals’ Tavalisse, which posted sales of $108 million and $105 million respectively in 2024.
The composition-of-matter patent for Promacta expired in the U.S. in July 2025. The FDA granted its first generic approval to Annora in April 2024, awarding a 180-day exclusivity period. In January 2025, a generic from Hetero also received FDA approval. Additional companies with tentative approvals include Actavis, Amneal, and Teva.
Novartis holds multiple patents and exclusivities protecting Promacta, with the last outstanding orphan drug exclusivity set to expire in November 2025. Legal challenges and patent term adjustments continue to shape the timeline for generic entry, with the estimated generic launch date currently around early 2026.
Overall, Promacta remains a key revenue driver for Novartis, but the approaching patent cliff and increasing generic competition are expected to pressure sales in the coming years.
Company: Johnson & Johnson
2024 U.S. sales: $1.08 billion
For the past decade, golimumab—marketed as Simponi (subcutaneous injection) and Simponi Aria (intravenous infusion)—has been a consistent blockbuster for Johnson & Johnson. The drug first surpassed $1 billion in annual global sales in 2014, a few years after its initial FDA approvals in 2009 for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Over the following years, as Simponi gained additional indications, sales steadily increased, peaking at just under $2.28 billion in 2021.
Although revenues have since stabilized, they remain strong, with Simponi generating $2.19 billion globally in 2024, split nearly evenly between U.S. and international markets.
However, Simponi’s market position faces uncertainty as biosimilar competition approaches in the U.S. The U.S. composition-of-matter patent for golimumab expired in 2024, paving the way for biosimilar entrants. While Simponi has not yet faced the extensive biosimilar competition seen by J&J’s Stelara, at least two biosimilars are in development, with the first potentially launching in late 2025 pending FDA approval.
Teva Pharmaceuticals and Alvotech, who previously developed biosimilars for Humira and Stelara, announced in January 2025 that the FDA accepted their biologics license application for their golimumab biosimilar, AVT05, with a decision expected in the fourth quarter of 2025.
Separately, Bio-Thera Solutions is developing a Simponi biosimilar, BAT2506. In February 2025, the company submitted an application for BAT2506 in Europe and granted exclusive U.S. rights to Accord BioPharma, though the drug has not yet been submitted to the FDA.
In response to looming biosimilar competition, J&J continues to support Simponi’s market presence. In December 2024, the company submitted an FDA application to expand Simponi’s label to include children aged 2 and older with moderately to severely active ulcerative colitis, an indication currently approved only for adults.
J&J has not publicly commented on Simponi’s loss of exclusivity in recent earnings calls, which have focused primarily on Stelara’s biosimilar challenges. However, the company completed the takeover of European distribution rights for Simponi and Remicade from Merck in the fourth quarter of 2024. This transition contributed to a 32% year-over-year increase in international Simponi sales during that period, while U.S. sales grew modestly by 1.3%.
Overall, Simponi remains a significant product for J&J, but the expiration of its core patent and the arrival of biosimilars in the U.S. market mark a pivotal moment for the drug’s future growth.
Company: Biogen
2024 U.S. sales: $920 million
Biogen’s multiple sclerosis (MS) drug Tysabri has faced the prospect of biosimilar competition since the FDA approved Sandoz’s biosimilar, Tyruko, in 2023. After a delay, Sandoz is now preparing for a planned U.S. launch of Tyruko in 2025.
Tysabri, first approved in 2004 for MS and in 2008 for Crohn’s disease, became a blockbuster by 2009. Although its sales have declined from a peak of $2.06 billion in 2021, Tysabri remains a key contributor to Biogen’s MS portfolio, with U.S. sales totaling $920 million in 2024.
Biogen has vigorously defended its market position, filing a 2022 patent lawsuit against Sandoz and its partner Polpharma, accusing them of attempting to “reap the benefits of Biogen’s hard work and success.” Despite these efforts, Tyruko received FDA approval in August 2023 as the first biosimilar to Tysabri for relapsing forms of MS and Crohn’s disease.
While Tyruko is already marketed in England and Germany, its U.S. launch has been delayed due to the need for FDA approval of a companion John Cunningham virus (JCV) antibody test. JCV antibodies are a known risk factor for progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection linked to Tysabri use. Biogen pioneered JCV antibody testing with its STRATIFY assay, approved in 2012 and used alongside Tysabri.
Sandoz developed its own JCV assay, ImmunoWELL, designed to closely match Biogen’s test. The company initially targeted a 2024 U.S. launch but postponed it to 2025, citing longer-than-expected FDA review of the JCV assay. Despite the delay, Tyruko remains a key launch priority for Sandoz in 2025.
In Europe, Tyruko’s introduction has coincided with reports of complications following patient switches from Tysabri, prompting Sandoz to investigate the issue at a London hospital.
Overall, Biogen’s MS sales declined 7% in 2024 amid biosimilar competition to Tysabri in Europe and generic challenges to other MS therapies, leading the company to focus more on new product launches.
Company: Novartis
2024 U.S. sales: $848 million
While Novartis’ loss of exclusivity for Entresto dominates headlines in 2025, its chronic myeloid leukemia (CML) therapy Tasigna is also poised to face generic competition this year. Originally approved in 2007, Tasigna’s composition-of-matter patent has expired in the U.S. and Europe, opening the door for generics, Novartis noted in its latest annual report.
Novartis expects generic versions of Tasigna to enter the U.S. market around mid-2025. In 2024, Tasigna generated $848 million in U.S. sales, while global revenue declined 8% to $1.7 billion, a drop attributed to “lower demand and increasing competition” across all regions.
Several companies—including Apotex, MSN Laboratories, and Hetero Labs—have secured tentative FDA approvals for their Tasigna generics. Apotex was the first to receive preliminary approval in January 2024.
Despite limited generic competition so far, Tasigna faces pressure from alternative CML treatments. In November 2024, Azurity Pharmaceuticals received FDA approval for Danziten, a reformulated version of nilotinib that does not require fasting. Azurity’s CEO highlighted that unlike Tasigna, Danziten’s label lacks a boxed warning mandating administration on an empty stomach, offering greater convenience for patients.
Novartis has also engaged proactively with generic manufacturers. In June 2023, the company signed a sublicense agreement via the United Nations’ Medicines Patent Pool, permitting four generic drugmakers to supply Tasigna copies to 44 low- and middle-income countries. This agreement is part of the Access to Oncology Medicines Coalition formed in 2022.
While Tasigna’s core patents have expired or are nearing expiration, several secondary patents and exclusivities remain active, with some extending into the late 2020s. The drug holds multiple orphan drug exclusivities, the last of which expires in 2029, potentially delaying broader generic entry.
Overall, Tasigna’s upcoming patent cliff and expanding generic approvals signal significant market shifts in 2025, challenging Novartis to adapt amid evolving competitive dynamics in CML treatment.
Company: AstraZeneca
2024 U.S. sales: $751 million
Alongside SGLT2 inhibitor Farxiga, AstraZeneca’s blood thinner Brilinta was launched to drive cardiometabolic growth following the costly loss of exclusivity for Crestor. Initially approved in 2011 to reduce secondary cardiovascular events in patients with acute coronary syndromes, Brilinta’s label expanded in 2015 to extend use beyond the first year. In 2020, it gained further approvals to reduce the risk of first heart attack or stroke in certain high-risk patients and in select stroke populations.
However, Brilinta faced clinical setbacks. In 2016, it failed two phase 3 trials—Socrates and Euclid—in peripheral artery disease (PAD). In Socrates, Brilinta did not outperform aspirin in preventing strokes, heart attacks, or death. In Euclid, it failed to surpass Bristol Myers Squibb and Sanofi’s Plavix in preventing major adverse cardiac events.
When AstraZeneca CEO Pascal Soriot repelled Pfizer’s hostile takeover bid in 2014, he projected Brilinta sales of $3.5 billion by 2023. After the PAD trial failures, the company acknowledged this target was unattainable. Brilinta peaked at $1.59 billion globally in 2020. Its growth was further hampered by COVID-19’s impact on cardiovascular hospitalizations and China’s volume-based procurement (VBP) program, which pressured prices.
Generics are expected to enter the U.S. market in 2025. Brilinta’s main regulatory exclusivity expires on May 9, 2025, with an additional six months of pediatric exclusivity extending to November 9, according to the FDA’s Orange Book. Multiple companies—including Sandoz, Dr. Reddy’s Laboratories, and Torrent Pharmaceuticals—have tentative FDA approvals for their generic versions. AstraZeneca lists 2025 as the expiration year for a key patent on Brilinta.
A pharmacy benefit manager’s report predicted the first U.S. generics would launch in May 2025. AstraZeneca has fought generic challengers in court since 2015, reaching multiple settlements in 2020, 2022, and 2024 to manage market entry timing.
Despite these challenges, AstraZeneca remains optimistic. On its fourth-quarter 2024 earnings call, CEO Soriot expressed confidence in strong 2025 performance despite Brilinta’s impending loss of exclusivity and potential VBP inclusion for Farxiga and roxadustat.
With generics poised to capture significant market share, payers are expected to mandate substitutions, driving rapid uptake of lower-cost alternatives. This transition will require careful management to reassure patients about therapeutic equivalence amid changes in tablet appearance and packaging.
In summary, Brilinta’s patent cliff in mid-2025 marks a turning point, ushering in generic competition that will reshape the U.S. antiplatelet market and challenge AstraZeneca’s cardiometabolic portfolio.
Source & Reference: https://www.fiercepharma.com/special-reports/top-10-drugs-losing-us-exclusivity-2025
Company: Amgen
2024 U.S. sales: $4.39 billion
Amgen’s Prolia and Xgeva, which share the active ingredient denosumab, have enjoyed a strong market presence since their launch in 2010. Together, they reached blockbuster status early, with combined global sales of $1.22 billion in 2012.
By 2024, both drugs continued to grow globally: Prolia’s sales rose 8% year-over-year to $4.37 billion, while Xgeva increased 5% to $2.23 billion. In the U.S., Prolia and Xgeva generated $4.39 billion combined, with Prolia’s sales up 6% and Xgeva’s down 1%. Prolia was Amgen’s top-selling drug in 2024, with Xgeva ranking third.
The two drugs serve different indications and dosing schedules. Prolia primarily treats osteoporosis in men and postmenopausal women at high fracture risk, while Xgeva is used to prevent skeletal-related events in cancer patients with bone metastases. Denosumab works by binding to RANKL, blocking its interaction with the receptor RANK, thereby inhibiting osteoclast-mediated bone resorption.
The key RANKL antibody patent protecting Prolia and Xgeva expired on February 19, 2025.
Sandoz was the first to receive FDA approval for interchangeable biosimilars referencing Prolia and Xgeva, launching Jubbonti and Wyost in March 2024. However, as is typical with major blockbusters, Amgen initiated patent litigation against Sandoz in March 2023, asserting infringement of 21 patents expiring as late as 2037. The companies settled in March 2024, with Sandoz agreeing to launch its biosimilars in the U.S. no earlier than May 31, 2025, or sooner under certain conditions tied to market competition.
In January 2025, Amgen also settled with Celltrion, permitting the Korean company to launch its denosumab biosimilars in the U.S. as early as June 1, 2025. Celltrion announced FDA approval for these biosimilars earlier that month.
Amgen continues to pursue legal action against Samsung Bioepis, Fresenius Kabi, and Accord BioPharma, with their cases consolidated for coordinated pretrial proceedings in New Jersey federal court.
Meanwhile, Shanghai Henlius Biotech and partner Organon had their biosimilar HLX14 accepted for FDA review in October 2024. Amneal, partnered with Fresenius Kabi’s mAbxience, also submitted two denosumab biosimilars for FDA review recently.
Despite the impending biosimilar competition, Prolia and Xgeva remain significant contributors to Amgen’s portfolio. In the first quarter of 2025, Xgeva sales increased 1% year-over-year to $566 million, though Amgen expects sales erosion later in the year due to biosimilars. Prolia’s first-quarter sales rose 10% to $1.1 billion, driven by volume growth offsetting pricing pressures.
Overall, Amgen’s strategic settlements and ongoing legal efforts aim to manage biosimilar competition while maintaining strong sales momentum for Prolia and Xgeva in a changing market landscape.
4. Entresto
Disease: Heart failureCompany: Novartis
2024 U.S. sales: $4.05 billion
Novartis is preparing for the potential entry of generic versions of Entresto in the U.S. this year, while vigorously defending its blockbuster heart failure drug. Entresto, approved by the FDA in 2015 for heart failure treatment, faces a key patent expiration in July 2025. This patent, covering the sacubitril-valsartan combination, is central to Novartis’ market exclusivity, which the company forecasts will end in mid-2025, subject to ongoing patent and regulatory litigation.
Multiple generic manufacturers—including Torrent, Dr. Reddy’s, Zydus, MSN, Alkem, and Lupin—have secured FDA approvals for their Entresto biosimilars or generics. Since 2020, Novartis has actively pursued legal action against several of these companies, resulting in confidential settlements and mixed legal outcomes.
A focal point of recent patent disputes involves MSN Pharmaceuticals, which received FDA approval for its Entresto generic in July 2024. Novartis responded by suing the FDA, alleging that the approval led to labeling that “inappropriately rewrites Entresto’s approved indication.” The FDA rejected Novartis’ Citizen Petition to block other generics, and a federal judge upheld MSN’s approval in October 2024.
Novartis also sought to block MSN’s generic launch through injunctions, but a Delaware judge denied the request in August 2024. Although Novartis appealed, it again lost in federal court in December. However, in January 2025, the U.S. Court of Appeals for the Federal Circuit ordered MSN to delay its launch “until further notice” while the court reviews Novartis’ efforts to extend patent protection.
In a significant January 2025 ruling, the Federal Circuit upheld the validity of Novartis’ key Entresto patent, reversing an earlier district court decision that had invalidated it. Novartis plans to enforce this patent through its pediatric exclusivity period, which expires in July 2025.
Entresto remains Novartis’ top-selling drug, generating approximately $7.8 billion in net sales in 2024. Beyond patent challenges, the drug is among the first subject to Medicare price negotiations under the Inflation Reduction Act, effective in early 2026. Novartis CEO Vas Narasimhan has expressed confidence that the company can manage the impact of these price reductions, noting that the affected drugs are nearing patent expiration and companies have been preparing alternative revenue streams.
Overall, while Novartis faces mounting generic competition and pricing pressures, the company continues to leverage legal strategies and patent protections to defend Entresto’s market position through mid-2025 and beyond.
5. Soliris
Diseases: Paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), neuromyelitis optica spectrum disorder (NMOSD)Company: AstraZeneca
2024 U.S. sales: $1.52 billion
AstraZeneca’s Soliris has enjoyed nearly two decades of market exclusivity since its 2007 FDA approval for paroxysmal nocturnal hemoglobinuria (PNH). Now, as biosimilar competition looms, AstraZeneca is leveraging its follow-up drug, Ultomiris, to sustain its leadership in rare complement-mediated diseases.
AstraZeneca acquired Soliris through its $39 billion purchase of Alexion Pharmaceuticals in 2021. Since then, Soliris has remained a significant revenue driver, though sales have declined recently as the company has shifted focus to Ultomiris. Approved in 2018 for the same indications, Ultomiris benefits from a longer patent life, with exclusivity extending to 2035. In 2024, Ultomiris surpassed Soliris in global sales, generating $3.9 billion compared to Soliris’ $2.59 billion. AstraZeneca attributes Soliris’ 18% worldwide sales decline to the “successful conversion” of patients to Ultomiris.
Alongside Soliris and Ultomiris, AstraZeneca markets Voydeya, a recently approved add-on therapy, aiming to maintain dominance in the PNH market despite challenges from Novartis’ oral PNH drug Fabhalta and Apellis’ C3 inhibitor Empaveli. Biosimilars have already impacted Soliris sales in Europe, but the U.S. market will face its first biosimilar launches this year.
Amgen’s Soliris biosimilar, Bkemv (eculizumab-aeeb), received FDA approval in May 2024 as the first interchangeable biosimilar for PNH and aHUS. The interchangeable designation allows pharmacy-level substitution without prescriber approval. Under a 2020 settlement with Alexion, Amgen is set to launch Bkemv in the U.S. in the second quarter of 2025. The FDA has confirmed that Bkemv is “highly similar with no clinically meaningful differences” from Soliris and carries the same boxed warning and Risk Evaluation and Mitigation Strategy (REMS) due to the risk of serious meningococcal infections.
Samsung Bioepis’ Epysqli (eculizumab-aagh), the second FDA-approved Soliris biosimilar, gained approval in July 2024 for PNH, aHUS, and later expanded indications to include generalized myasthenia gravis. In January 2025, Teva Pharmaceuticals entered a licensing and commercialization agreement with Samsung Bioepis to market Epysqli in the U.S., while Samsung handles development, manufacturing, and supply. Epysqli is offered at a 30% discount to Soliris’ wholesale acquisition cost and is already marketed in Europe. The FDA has provisionally designated Epysqli as interchangeable once Amgen’s exclusivity expires.
The U.S. launch of Epysqli was announced in April 2025, marking a significant expansion of biosimilar options for patients with rare complement-mediated disorders. Both Bkemv and Epysqli carry the same safety profiles and are subject to REMS programs to mitigate serious infection risks.
AstraZeneca’s strategic transition from Soliris to Ultomiris, combined with the introduction of biosimilars, reflects the evolving competitive landscape in rare disease treatment. While Soliris faces biosimilar erosion, Ultomiris and Voydeya position AstraZeneca to maintain a strong presence in this specialized market.
6. Promacta
Diseases: Thrombocytopenia, aplastic anemiaCompany: Novartis
2024 U.S. sales: $1.18 billion
While much attention surrounds Novartis’ impending loss of exclusivity for its heart failure drug Entresto, two other blockbusters—Promacta and Tasigna—are also set to face generic competition in the U.S. in 2025. For forecasting, Novartis projects all three drugs will lose U.S. market exclusivity by mid-2025, subject to ongoing patent and regulatory developments.
Promacta, originally developed by Ligand and GSK and acquired by Novartis in 2014 as part of a $16 billion oncology portfolio purchase, has steadily grown since its 2008 FDA approval. The drug, known as Revolade in Europe, expanded its label to include first-line aplastic anemia in 2018, the year it first achieved blockbuster status. In 2024, Promacta generated $2.2 billion globally, with $1.2 billion from the U.S., marking a 2% decline attributed by Novartis to reduced proactive promotion.
Promacta is a daily oral therapy for thrombocytopenia and competes primarily with Amgen’s Nplate, a once-weekly injection approved in 2008 for chronic immune thrombocytopenia. Nplate’s 2024 sales reached $1.46 billion, down 1% from the prior year. Other competitors include Sobi’s Doptelet and Rigel Pharmaceuticals’ Tavalisse, which posted sales of $108 million and $105 million respectively in 2024.
The composition-of-matter patent for Promacta expired in the U.S. in July 2025. The FDA granted its first generic approval to Annora in April 2024, awarding a 180-day exclusivity period. In January 2025, a generic from Hetero also received FDA approval. Additional companies with tentative approvals include Actavis, Amneal, and Teva.
Novartis holds multiple patents and exclusivities protecting Promacta, with the last outstanding orphan drug exclusivity set to expire in November 2025. Legal challenges and patent term adjustments continue to shape the timeline for generic entry, with the estimated generic launch date currently around early 2026.
Overall, Promacta remains a key revenue driver for Novartis, but the approaching patent cliff and increasing generic competition are expected to pressure sales in the coming years.
7. Simponi/Simponi Aria
Diseases: Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, polyarticular juvenile idiopathic arthritisCompany: Johnson & Johnson
2024 U.S. sales: $1.08 billion
For the past decade, golimumab—marketed as Simponi (subcutaneous injection) and Simponi Aria (intravenous infusion)—has been a consistent blockbuster for Johnson & Johnson. The drug first surpassed $1 billion in annual global sales in 2014, a few years after its initial FDA approvals in 2009 for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Over the following years, as Simponi gained additional indications, sales steadily increased, peaking at just under $2.28 billion in 2021.
Although revenues have since stabilized, they remain strong, with Simponi generating $2.19 billion globally in 2024, split nearly evenly between U.S. and international markets.
However, Simponi’s market position faces uncertainty as biosimilar competition approaches in the U.S. The U.S. composition-of-matter patent for golimumab expired in 2024, paving the way for biosimilar entrants. While Simponi has not yet faced the extensive biosimilar competition seen by J&J’s Stelara, at least two biosimilars are in development, with the first potentially launching in late 2025 pending FDA approval.
Teva Pharmaceuticals and Alvotech, who previously developed biosimilars for Humira and Stelara, announced in January 2025 that the FDA accepted their biologics license application for their golimumab biosimilar, AVT05, with a decision expected in the fourth quarter of 2025.
Separately, Bio-Thera Solutions is developing a Simponi biosimilar, BAT2506. In February 2025, the company submitted an application for BAT2506 in Europe and granted exclusive U.S. rights to Accord BioPharma, though the drug has not yet been submitted to the FDA.
In response to looming biosimilar competition, J&J continues to support Simponi’s market presence. In December 2024, the company submitted an FDA application to expand Simponi’s label to include children aged 2 and older with moderately to severely active ulcerative colitis, an indication currently approved only for adults.
J&J has not publicly commented on Simponi’s loss of exclusivity in recent earnings calls, which have focused primarily on Stelara’s biosimilar challenges. However, the company completed the takeover of European distribution rights for Simponi and Remicade from Merck in the fourth quarter of 2024. This transition contributed to a 32% year-over-year increase in international Simponi sales during that period, while U.S. sales grew modestly by 1.3%.
Overall, Simponi remains a significant product for J&J, but the expiration of its core patent and the arrival of biosimilars in the U.S. market mark a pivotal moment for the drug’s future growth.
8. Tysabri
Diseases: Multiple sclerosis, Crohn’s diseaseCompany: Biogen
2024 U.S. sales: $920 million
Biogen’s multiple sclerosis (MS) drug Tysabri has faced the prospect of biosimilar competition since the FDA approved Sandoz’s biosimilar, Tyruko, in 2023. After a delay, Sandoz is now preparing for a planned U.S. launch of Tyruko in 2025.
Tysabri, first approved in 2004 for MS and in 2008 for Crohn’s disease, became a blockbuster by 2009. Although its sales have declined from a peak of $2.06 billion in 2021, Tysabri remains a key contributor to Biogen’s MS portfolio, with U.S. sales totaling $920 million in 2024.
Biogen has vigorously defended its market position, filing a 2022 patent lawsuit against Sandoz and its partner Polpharma, accusing them of attempting to “reap the benefits of Biogen’s hard work and success.” Despite these efforts, Tyruko received FDA approval in August 2023 as the first biosimilar to Tysabri for relapsing forms of MS and Crohn’s disease.
While Tyruko is already marketed in England and Germany, its U.S. launch has been delayed due to the need for FDA approval of a companion John Cunningham virus (JCV) antibody test. JCV antibodies are a known risk factor for progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection linked to Tysabri use. Biogen pioneered JCV antibody testing with its STRATIFY assay, approved in 2012 and used alongside Tysabri.
Sandoz developed its own JCV assay, ImmunoWELL, designed to closely match Biogen’s test. The company initially targeted a 2024 U.S. launch but postponed it to 2025, citing longer-than-expected FDA review of the JCV assay. Despite the delay, Tyruko remains a key launch priority for Sandoz in 2025.
In Europe, Tyruko’s introduction has coincided with reports of complications following patient switches from Tysabri, prompting Sandoz to investigate the issue at a London hospital.
Overall, Biogen’s MS sales declined 7% in 2024 amid biosimilar competition to Tysabri in Europe and generic challenges to other MS therapies, leading the company to focus more on new product launches.
9. Tasigna
Disease: Chronic myeloid leukemiaCompany: Novartis
2024 U.S. sales: $848 million
While Novartis’ loss of exclusivity for Entresto dominates headlines in 2025, its chronic myeloid leukemia (CML) therapy Tasigna is also poised to face generic competition this year. Originally approved in 2007, Tasigna’s composition-of-matter patent has expired in the U.S. and Europe, opening the door for generics, Novartis noted in its latest annual report.
Novartis expects generic versions of Tasigna to enter the U.S. market around mid-2025. In 2024, Tasigna generated $848 million in U.S. sales, while global revenue declined 8% to $1.7 billion, a drop attributed to “lower demand and increasing competition” across all regions.
Several companies—including Apotex, MSN Laboratories, and Hetero Labs—have secured tentative FDA approvals for their Tasigna generics. Apotex was the first to receive preliminary approval in January 2024.
Despite limited generic competition so far, Tasigna faces pressure from alternative CML treatments. In November 2024, Azurity Pharmaceuticals received FDA approval for Danziten, a reformulated version of nilotinib that does not require fasting. Azurity’s CEO highlighted that unlike Tasigna, Danziten’s label lacks a boxed warning mandating administration on an empty stomach, offering greater convenience for patients.
Novartis has also engaged proactively with generic manufacturers. In June 2023, the company signed a sublicense agreement via the United Nations’ Medicines Patent Pool, permitting four generic drugmakers to supply Tasigna copies to 44 low- and middle-income countries. This agreement is part of the Access to Oncology Medicines Coalition formed in 2022.
While Tasigna’s core patents have expired or are nearing expiration, several secondary patents and exclusivities remain active, with some extending into the late 2020s. The drug holds multiple orphan drug exclusivities, the last of which expires in 2029, potentially delaying broader generic entry.
Overall, Tasigna’s upcoming patent cliff and expanding generic approvals signal significant market shifts in 2025, challenging Novartis to adapt amid evolving competitive dynamics in CML treatment.
10. Brilinta
Diseases: Acute coronary syndrome, coronary artery disease, acute ischemic stroke, high-risk transient ischemic attackCompany: AstraZeneca
2024 U.S. sales: $751 million
Alongside SGLT2 inhibitor Farxiga, AstraZeneca’s blood thinner Brilinta was launched to drive cardiometabolic growth following the costly loss of exclusivity for Crestor. Initially approved in 2011 to reduce secondary cardiovascular events in patients with acute coronary syndromes, Brilinta’s label expanded in 2015 to extend use beyond the first year. In 2020, it gained further approvals to reduce the risk of first heart attack or stroke in certain high-risk patients and in select stroke populations.
However, Brilinta faced clinical setbacks. In 2016, it failed two phase 3 trials—Socrates and Euclid—in peripheral artery disease (PAD). In Socrates, Brilinta did not outperform aspirin in preventing strokes, heart attacks, or death. In Euclid, it failed to surpass Bristol Myers Squibb and Sanofi’s Plavix in preventing major adverse cardiac events.
When AstraZeneca CEO Pascal Soriot repelled Pfizer’s hostile takeover bid in 2014, he projected Brilinta sales of $3.5 billion by 2023. After the PAD trial failures, the company acknowledged this target was unattainable. Brilinta peaked at $1.59 billion globally in 2020. Its growth was further hampered by COVID-19’s impact on cardiovascular hospitalizations and China’s volume-based procurement (VBP) program, which pressured prices.
Generics are expected to enter the U.S. market in 2025. Brilinta’s main regulatory exclusivity expires on May 9, 2025, with an additional six months of pediatric exclusivity extending to November 9, according to the FDA’s Orange Book. Multiple companies—including Sandoz, Dr. Reddy’s Laboratories, and Torrent Pharmaceuticals—have tentative FDA approvals for their generic versions. AstraZeneca lists 2025 as the expiration year for a key patent on Brilinta.
A pharmacy benefit manager’s report predicted the first U.S. generics would launch in May 2025. AstraZeneca has fought generic challengers in court since 2015, reaching multiple settlements in 2020, 2022, and 2024 to manage market entry timing.
Despite these challenges, AstraZeneca remains optimistic. On its fourth-quarter 2024 earnings call, CEO Soriot expressed confidence in strong 2025 performance despite Brilinta’s impending loss of exclusivity and potential VBP inclusion for Farxiga and roxadustat.
With generics poised to capture significant market share, payers are expected to mandate substitutions, driving rapid uptake of lower-cost alternatives. This transition will require careful management to reassure patients about therapeutic equivalence amid changes in tablet appearance and packaging.
In summary, Brilinta’s patent cliff in mid-2025 marks a turning point, ushering in generic competition that will reshape the U.S. antiplatelet market and challenge AstraZeneca’s cardiometabolic portfolio.
Source & Reference: https://www.fiercepharma.com/special-reports/top-10-drugs-losing-us-exclusivity-2025
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