10 Drugs Losing Exclusivity This Year

A wave of high-profile drugs is set to lose patent protection in 2025. Here’s a closer look at the 10 most anticipated.

While forcing pharmaceutical giants to grapple with lost exclusivity and diminished market share, patent cliffs offer increased access to essential medicines. As competitors develop generic alternatives, patients benefit from reduced costs and improved accessibility.

Stelara (ustekinumab)

New Jersey-based Johnson & Johnson's (NYSE: JNJ) remarkably successful immunology drug Stelara closed in over $6.72 billion in 2024 US sales. On January 1 of this year, however, Amgen (NASDAQ: AMGN) launched competing biosimilar drug Wezlana, following a settlement between the two over a patent infringement claim from J&J that forced the former to delay the launch until this year.

After resolving a patent dispute that had held up its market entry, Wezlana stands among six more biosimilar alternatives that have each gotten FDA approval and are set for launch. With total worldwide sales over $10.3 billion in 2024, J&J’s Stelara remains optimistic amid the deluge of new competition, as CEO Duato projects a 3% annual growth rate for 2025. The company believes it will recoup a portion of Stelara’s lost revenue as patients switch to its newer immunology drug Tremfya, an offering for which JNJ is seeking to add Crohn's disease to a list of existing FDA approvals for psoriatic arthritis and psoriasis.

Eylea (aflibercept)

New York-based Regeneron's (NASDAQ: REGN) ophthalmic powerhouse Eylea generated a substantial $4.77 billion in US sales in 2024, solidifying its position in the treatment of macular degeneration and diabetic retinopathy. However, the landscape is shifting. Biosimilar competitors have now entered the field, challenging Eylea’s formerly unchallenged dominance. This increased competition will put pressure on Eylea’s market share. Investors are now closely monitoring Regeneron’s strategic responses to maintain its position within the market.

Amgen’s Pavblu, the first U.S. biosimilar to Eylea, launched in November and achieved $31 million in sales in its first nine weeks. The launch was enabled by a West Virginia court ruling that favored Amgen, in contrast to earlier decisions blocking the launch of Eylea biosimilars from Biocon, Biogen, and Samsung Bioepis until 2027.

Prolia/Xgeva (denosumab)

Amgen's (NASDAQ: AMGN) bone health franchise, encompassing Prolia and Xgeva, achieved $4.39 billion in US sales during 2024, treating osteoporosis and skeletal-related diseases. As patents expire, the company prepares for generic competition. How Amgen manages the transition, and the degree to which it can protect its market share, is a key concern for shareholders, given Prolia was the company’s highest-selling medicine in 2024, and Xgeva its third.

Amgen's strategy to maximize the drug's potential across different indications has been a key factor in its success, but the transition to competition from generics will be a major test for Amgen's ability to maintain market share within the bone health treatment sector.

Entresto (sacubitril)

Switzerland-based Novartis (NYSE: NVS) is vigorously defending its blockbuster heart failure drug, Entresto (sacubitril/valsartan), against impending generic competition in the U.S., despite its key combination patent set to expire in July 2025. With $4.05 billion in U.S. sales in 2024, Entresto faces potential generic entry from nearly a dozen drugmakers, including Torrent and MSN.

After having pursued numerous lawsuits against generic manufacturers, resulting in confidential settlements and mixed legal outcomes, Novartis' attempts to block MSN's launch through both injunctions and a lawsuit against the FDA alleging improper labeling have been unsuccessful. The U.S. Court of Appeals for the Federal Circuit ordered MSN to delay its generic launch pending further review.

Entresto is one of the first drugs subject to Medicare price negotiations under the Inflation Reduction Act, although Novartis anticipates the impact to be manageable due to the drug's proximity to its patent cliff. And Entresto's journey to becoming a cornerstone heart failure treatment was marked by initial skepticism, followed by compelling clinical data that reshaped treatment guidelines and propelled the drug’s acceptance into the standard of care.

Solaris (eculizumab)

AstraZeneca's (NASDAQ: AZN) rare disease treatment Soliris brought in $1.52 billion in US sales in 2024. Soliris, used to treat rare conditions like paroxysmal nocturnal haemoglobinuria (PNH), faces imminent biosimilar competition in the U.S. after nearly two decades of market exclusivity since its 2007 approval.

Despite generating over $1 billion in 2024 U.S. sales, Soliris' global sales are declining due to AstraZeneca's strategic shift towards its follow-up drug, Ultomiris (ravulizumab), which boasts a 2035 patent expiration and sales that have surpassed those of Soliris globally, indicating a successful patient conversion strategy.

As the company prioritizes the drug’s successor, Ultomiris, while simultaneously leveraging its newly-approved add-on treatment, Voydeya, investors in the UK-based company have renewed confidence in its current portfolio.

Soliris, a drug with a staggering price tag, became a symbol of the ethical dilemmas surrounding rare disease treatments and the dual reality of balancing innovation with maintaining the accessibility of medicines. Biosimilars from Amgen (Bkemv) and Samsung Bioepis (Epysqli) are believed to help increase access to treatments for these rare diseases in ways that Soliris could not, potentially offering relief to patients burdened by the sky-high costs of the drug.

Promacta (eltrombopag)

Novartis' (NYSE: NVS) Promacta, used to treat thrombocytopenia and aplastic anemia, reached $1.18 billion in U.S. sales in 2024 and $2.2 billion globally. Novartis acquired Promacta in 2014 and expanded its indications, achieving blockbuster status in 2018 and surpassing $2 billion in global sales by 2022, turning the drug into a key player in managing platelet counts in patients with chronic liver disease and other conditions.

Despite a slight 2% global sales decline in 2024 due to reduced promotional efforts, Promacta faces increasing generic competition. Annora received the first FDA approval for a Promacta generic in April 2023, securing 180 days of exclusivity, followed by Hetero's approval in January 2024. Other companies with tentative approvals include Actavis, Amneal, and Teva.

Novartis is bracing for significant revenue impacts in 2025 due to the anticipated mid-year loss of U.S. market exclusivity for three blockbuster drugs: Entresto (aforementioned), Promacta, and Tasigna (mentioned below).

Simponi (golimumab)

Johnson & Johnson's (NYSE: JNJ) Simponi, with US sales of $1.08 billion in 2024, is now subject to biosimilar competition. Simponi, available as both a subcutaneous injection and intravenous infusion, achieved blockbuster status in 2014, with peak global sales reaching $2.28 billion in 2021 and remaining around $2.19 billion in 2024.

With Teva Pharmaceuticals and Alvotech developing biosimilar, AVT05, and a potential FDA approval and launch in late 2025, J&J is seeking to expand Simponi's label to include pediatric ulcerative colitis patients. J&J's earnings calls have focused more on Stelara's biosimilar competition, with Simponi's mentions limited to J&J's acquisition of European distribution rights, which resulted in a 32% year-over-year increase in international Simponi sales in Q4 2024.

Tysabri (natalizumab)

Biogen's (NASDAQ: BIIB) multiple sclerosis (MS) treatment, Tysabri, generated $920 million in US sales during 2024, and it set to face imminent biosimilar competition in the U.S. from Sandoz's Tyruko, following FDA approval in 2023.

Tysabri navigated a complex risk-benefit profile, with concerns about rare but serious side effects shaping its usage. The increasing biosimilar competition for Tysabri, coupled with generic pressures on other Biogen MS drugs, contributed to a 7% decline in Biogen's overall MS sales in 2024, prompting the company to focus on new product launches.

Tasigna (nilotinib)

Novartis (NYSE: NVS) faces impending generic competition for its chronic myeloid leukemia (CML) drug, Tasigna, which generated $848 million in U.S. sales in 2024. The projected entry of generics in mid-2025 coincides with a broader trend of declining global Tasigna sales, attributed to "lower demand and increasing competition." Several companies, including Apotex, MSN Laboratories, and Hetero Labs, have already secured tentative FDA approvals for their Tasigna generics, with Apotex achieving the first preliminary green light in January 2024. 2

Novartis' Tasigna, a targeted therapy for chronic myeloid leukemia, represented a significant advancement in cancer treatment, but its high cost raised questions about accessibility.

Brilinta (ticagrelor)

After grossing over $750 million in 2024 US sales, Cambridge (UK)-based AstraZeneca's (NASDAQ: AZN) antiplatelet medication, Brilinta, is now facing generic market entry. The blood-thinning drug initially showed great promise as a key growth driver following Crestor's loss of exclusivity, securing FDA approvals for secondary cardiovascular event prevention in 2011 and expanding its label in 2015 and 2020 to include primary prevention and stroke patients.

However, clinical setbacks, notably failed Phase 3 trials in peripheral artery disease (PAD) in 2016, dashed hopes of achieving the ambitious $3.5 billion sales target set by CEO Pascal Soriot, with peak global sales ultimately reaching only $1.59 billion in 2020. Sales were further hampered by COVID-19's impact on hospitalizations and China's volume-based procurement (VBP) program, and with generic competition expected in the U.S. by 2025, AstraZeneca is now shifting its focus to other medications like Farxiga after Brilinta’s use began being debated in the context of bleeding risk and cost-effectiveness.

As companies like Novartis and Astrazeneca (both of whom have multiple drugs that face generic competition this year) navigate the turbulent landscape and strategize for maintaining market share, a closer look finds that the impact of these patent cliffs extends beyond immediate revenue loss, forcing a fundamental reassessment of long-term R&D investment while simultaneously demanding effective communication of the value proposition for an updated, post-exclusivity portfolio.

The data for this article has been obtained from the FDA’s publication regarding Approved Drug Products with Therapeutic Equivalence Evaluations, evaluating patent and exclusivity information. Read the FDA’s Orange Book here.