2025 Pharmaceutical Pipeline: Major Patent Expirations Set to Transform Drug Market with Generics and Biosimilars
核心洞察
The US pharmaceutical market is poised for significant change in 2025 as several blockbuster drugs including Xarelto, Entresto, and Stelara face patent expirations, opening the door to generic and biosimilar competition.
Multiple biosimilars for ustekinumab (Stelara) are entering the market in 2025, with Wezlana already launched in January as the first interchangeable biosimilar, while other major drugs like ticagrelor and denosumab will also face competition.
The pharmaceutical pipeline continues to expand with innovative therapies for cancer and neurological disorders, alongside the Medicare Drug Price Negotiation program which will further impact pricing dynamics for high-cost medications.
2025 is shaping up to be a transformative year for the pharmaceutical industry as several blockbuster medications lose patent protection and face generic and biosimilar competition. This shift promises to reshape the market landscape while potentially improving medication affordability and access for patients.
Major Patent Expirations and Generic Competition
Twenty small molecule drugs are expected to face generic competition in 2025, including several blockbuster agents with annual sales exceeding $1.5 billion. Among the most significant patent expirations:
Rivaroxaban (Xarelto) - This direct-acting oral anticoagulant will see its solid oral formulation patent expire in May 2025. The FDA has already approved the first generic versions of the 2.5 mg tablets in March 2025, specifically for reducing major cardiovascular and thrombotic events in patients with coronary artery disease (搜索) and peripheral artery disease (搜索).
Sacubitril/Valsartan (Entresto) - This heart failure (搜索) medication is expected to face generic competition as early as mid-2025 following the expiration of a key combination patent in July. Multiple manufacturers have already received FDA approval to market generic versions, including Alembic Pharmaceutical Limited and Laurel Labs Limited. A recent appellate court decision ruled against Novartis, weakening its ability to delay generic market entry.
Ticagrelor (Brilinta) - Originally launched with high expectations as part of AstraZeneca's cardiometabolic pipeline strategy, ticagrelor never reached its projected $3.5 billion annual revenue target, peaking at $1.59 billion globally in 2020. Generic versions are expected to enter the US market in 2025, likely prompting formulary changes and payer-mandated substitutions.
Biosimilar Wave for Major Biologics
The biologics market is also experiencing significant change, with several important products facing biosimilar competition:
Ustekinumab (Stelara) - This cornerstone therapy for autoimmune conditions such as plaque psoriasis (搜索), psoriatic arthritis (搜索), Crohn disease (搜索), and ulcerative colitis (搜索) saw its primary composition-of-matter patent expire in September 2023. The first biosimilar, Wezlana (ustekinumab-auub), launched on January 1, 2025, with an FDA interchangeability designation allowing for automatic substitution at the pharmacy level. Six additional FDA-approved biosimilars are expected to enter the market throughout 2025, including products from Teva (搜索), Sandoz, Fresenius Kabi, Accord, Biocon Biologics, and Celltrion.
Denosumab (Prolia) - Used for treating osteoporosis (搜索) in postmenopausal women at high risk for fracture, denosumab's primary US patent expired in February 2025. Sandoz's biosimilars, denosumab-bbdz (Jubbonti) and denosumab-bbgn (Wyost), were approved in March 2024 and are expected to launch May 31, 2025, under a settlement with Amgen. Samsung Bioepis' biosimilars, denosumab-bexm (Ospomyv) and denosumab-bkzt (Xbryk), received approval in February 2025.
Patent Thickets and Legal Challenges
The path to market for generics and biosimilars is not without obstacles. Leslie Fish, PharmD, RPh, senior vice president of pharmacy at IPD Analytics, highlighted several issues preventing certain products from coming to market, particularly legal challenges. These include:
- Companies choosing to launch products at risk
- Delayed launches as part of settlement agreements
- Skinny labels preventing generics from accessing the originator's full market
- Patent thickets, where originator manufacturers obtain subsequent patents on a product after it's been on the market
"It's like baking a cake. You want to put a patent on your cake, but you not only have a patent on the cake. You have a patent on that particular wooden spoon that you stir it with. You have a patent on the oven that you used it with. The patents end up working [to extend exclusivity] together and that's how these patent thickets occur," Fish explained.
Pipeline Innovation Continues
Despite the focus on patent expirations, pharmaceutical innovation continues to advance. Nine new drug applications (NDAs) are awaiting FDA approval under the 505(b)(2) pathway, including three therapies for migraine, two for hypertension, one for chronic kidney disease, one for fibromyalgia, one nasal agent for anaphylactic reactions, and one for deep vein thrombosis or acute pulmonary embolism.
Several branded medicines are also seeking new indications, including brexpiprazole (Rexulti) for posttraumatic stress disorder, tirzepatide (Zepbound) for heart failure (搜索) in patients with obesity, and finerenone (Kerendia) for heart failure and chronic kidney disease.
Maria M. Lowe, PharmD, BCPS, associate vice president of pharmaceutical intelligence at the Institute for Clinical and Economic Review, highlighted anticipated agents in development, including gene therapies for epidermolysis bullosa, a glycogen-like peptide-2 agonist for short bowel syndrome, therapies for Fabry disease, regimens for hypercholesterolemia, and treatments for Duchenne muscular dystrophy.
Medicare Drug Price Negotiation Impact
Adding another layer of complexity to the pharmaceutical landscape is the Medicare Drug Price Negotiation program established by the Inflation Reduction Act of 2022. The first negotiated prices will take effect in 2026 for 10 Part D drugs, with another 15 Part D drugs already selected for 2027 pricing implementation. Many of the drugs included—such as apixaban, rivaroxaban, sacubitril/valsartan, ustekinumab, and empagliflozin—are also scheduled to lose patent protection in the near future.
Negotiated prices under the program apply only to brand-name versions of drugs that do not yet face generic or biosimilar competition. If a generic or biosimilar product is approved and marketed, CMS can suspend or terminate the negotiation process for that brand-name drug. This dynamic may significantly impact therapy selection for Medicare beneficiaries and influence prescribing trends, formulary decisions, and patient counseling.
Implications for Healthcare Providers and Patients
For healthcare providers, these market changes will require careful management of formulary transitions and patient education. Pharmacists will play a crucial role in:
- Ensuring continuity of care during product switches
- Educating patients about therapeutic equivalence
- Navigating state-dependent substitution regulations for biosimilars
- Understanding payer coverage changes and cost implications
As the pharmaceutical landscape evolves, the intersection of patent expirations, biosimilar competition, and government price negotiations will continue to reshape medication access and affordability, potentially benefiting patients while creating new challenges for healthcare systems to navigate.