A Pharmacist’s Guide to Blockbuster Patent Expirations: 2025 and Beyond

Introduction

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This year is shaping up to be a turning point in the pharmaceutical landscape, with several blockbuster drugs losing their patent protection and opening the floodgates for generics and biosimilars. These medications, many of which generate billions in annual revenue, have long held exclusive positions on pharmacy shelves. Now, as their exclusivity ends, a new chapter begins in the race to bring more affordable alternatives to the market.

This transition isn’t without resistance. Behind the scenes, legal battles are being waged as brand-name manufacturers fight to delay competition through patent litigation and regulatory maneuvers. But the writing is on the wall: generic and biosimilar challengers are gaining momentum. For community pharmacists, this shift brings new responsibilities and opportunities, from managing inventory changes to counseling patients on alternative therapies. Understanding which drugs are on the cusp of losing exclusivity is essential for preparing both practice and patients for what lies ahead.

Ticagrelor (Brilinta; AstraZeneca)

Ticagrelor (Brilinta; AstraZeneca) was originally launched with high expectations. It was part of AstraZeneca’s cardiometabolic pipeline strategy aimed at offsetting revenue lost after the patent expiration of rosuvastatin (Crestor; AstraZeneca).¹ Approved by the FDA in 2011 to reduce the risk of cardiovascular events in patients with acute coronary syndromes, ticagrelor later received label expansions that broadened its use beyond the first year of therapy and into primary prevention settings for high-risk individuals.²

However, despite these developments, the product's commercial trajectory was tempered by clinical and market setbacks. Two phase 3 trials, SOCRATES and EUCLID, failed to demonstrate superiority over aspirin and clopidogrel (Plavix; Bristol Myers Squibb/Sanofi), respectively, in patients with peripheral artery disease.³ These disappointments, combined with a decline in cardiovascular hospitalizations during the COVID-19 pandemic and the impact of China’s volume-based procurement pricing strategy, curtailed growth. Although AstraZeneca once targeted $3.5 billion in annual revenue for ticagrelor by 2023, the product peaked at $1.59 billion globally in 2020 and never approached its initial forecast.⁴

Now, as generic versions are expected to enter the US market in 2025, pharmacists should anticipate formulary changes and payer-mandated substitutions. Ticagrelor was frequently positioned as a preferred oral P2Y12 inhibitor in some hospital-based protocols, and its generic availability may encourage outpatient continuity at a reduced cost. As with other agents in its class, adherence and bleeding risk remain critical counseling points.

Sacubitril/Valsartan (Entresto; Novartis)

With the expiration of a key combination patent scheduled for July 2025, sacubitril and valsartan (Entresto; Novartis) is expected to face generic competition in the United States as early as midyear. Novartis acknowledged this in its 2024 annual report, projecting a potential loss of exclusivity around mid-2025, though it emphasized that this forecast is subject to ongoing litigation and regulatory developments.¹ A recent appellate court decision ruled against the company, weakening its ability to delay generic market entry.⁵ Multiple manufacturers have already received FDA approval to market generic versions, including Alembic Pharmaceutical Limited, Laurel Labs Limited, and others.⁶

These approvals set the stage for staggered market launches and changes in payer dynamics, with insurers likely to favor generic substitution. Patients stabilized on the branded formulation may raise concerns over differences in tablet appearance or packaging; counseling will be essential to reassure patients of therapeutic equivalence.

Rivaroxaban (Xarelto; Bayer)

Rivaroxaban (Xarelto; Bayer), a direct oral anticoagulant (DOAC) widely prescribed for preventing stroke, venous thromboembolism, and recurrent cardiovascular events, is approaching its final patent expiration in 2025. The solid oral formulation patent, including pediatric exclusivity, is scheduled to expire in May 2025. In anticipation, the FDA approved the first generic versions of rivaroxaban 2.5-mg tablets in March 2025, indicated for reducing major cardiovascular and thrombotic events in patients with coronary artery disease and peripheral artery disease.⁷

In contrast, apixaban (Eliquis; Bristol Myers Squibb and Pfizer), another leading DOAC, has a more complex patent landscape. Although certain patents are set to expire in 2026, court rulings have delayed generic competition in the US until at least 2028. Bristol Myers Squibb expects generic entry for Eliquis to begin on April 1, 2028.⁸

Pharmacists should prepare for the introduction of generic rivaroxaban formulations, which will impact inventory management and prescribing trends. Ensuring continuity in patient adherence and confirming dose accuracy across varying tablet strengths will be essential.

Ustekinumab (Stelara; Janssen Biotech)

Ustekinumab (Stelara; Janssen Biotech) has been a cornerstone in the management of autoimmune conditions such as plaque psoriasis, psoriatic arthritis, Crohn disease, and ulcerative colitis. The primary composition-of-matter patent expired in September 2023, with additional patents extending into the 2030s. Following a settlement between Janssen and Amgen, the first biosimilar referencing Stelara, Wezlana (ustekinumab-auub), launched on January 1, 2025, and is currently distributed exclusively through Nuvaila.⁹ Wezlana holds an interchangeability designation from the FDA, allowing for automatic substitution at the pharmacy level without prescriber intervention. The product's approval was based on a randomized phase 3 trial demonstrating similar safety and efficacy to the reference product in patients with moderate to severe plaque psoriasis.⁹

Wezlana is the first of 7 biosimilars expected to enter the market in 2025. Additional FDA-approved biosimilars include ustekinumab-aekn (Selarsdi; Teva), ustekinumab-ttwe (Pyzchiva; Sandoz), ustekinumab-aauz (Otulfi; Fresenius Kabi), ustekinumab-srlf (Imuldosa; Accord), ustekinumab-kfce (Yesintek; Biocon Biologics), and ustekinumab-stba (Steqeyma; Celltrion).^10-12 Clinical guidelines often reserve ustekinumab for patients who have not responded to conventional systemic therapies or TNFα inhibitors due to its favorable safety profile and convenient dosing. Pharmacists should anticipate insurance-driven transitions and state-dependent substitution regulations. Counseling on biosimilar efficacy and safety will be crucial for patient confidence and prescriber alignment.

Pharmacists should anticipate insurance-driven transitions and state-dependent substitution regulations. Automatic substitution requires an FDA-designated interchangeable biosimilar.^13,14 Counseling on biosimilar efficacy and safety will be crucial for patient confidence and prescriber alignment.

Denosumab (Prolia; Amgen)

Denosumab (Prolia; Amgen) is approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture. Its primary US patent expired February 19, 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.¹⁵ Samsung Bioepis’ biosimilars, denosumab-bexm (Ospomyv) and denosumab-bkzt (Xbryk), were approved in February 2025.¹⁶

Biosimilar entry will influence payer coverage and may prompt switching protocols. Pharmacists must educate patients on administration and monitor for formulary transitions. Substitution rules vary by state and hinge on FDA interchangeability status.¹⁷

Medicare Drug Price Negotiation and Its Impact on Therapy Selection

The Inflation Reduction Act (IRA) of 2022 introduced sweeping reforms to Medicare drug pricing, including provisions that allow the Centers for Medicare & Medicaid Services (CMS) to negotiate prices for certain high-cost, single-source brand-name drugs. 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.^18,19 Many of the drugs included—such as apixaban, rivaroxaban, sacubitril and valsartan, ustekinumab, and empagliflozin (Jardiance; Boehringer Ingelheim)—are also scheduled to lose patent protection in the near future, raising important questions around therapy selection and market dynamics.

Negotiated prices under the IRA apply only to the brand-name versions of drugs that do not yet face generic or biosimilar competition. If a generic or biosimilar product is approved and marketed on a bona fide basis, CMS can suspend or terminate the negotiation process for that brand-name drug.²⁰ However, if the negotiated price is finalized and a generic enters later, the brand-name product will remain on the negotiated pricing list for the remainder of the price applicability year but will be removed from subsequent cycles.²⁰

This dynamic may impact how prescribers and payers approach therapy selection for Medicare beneficiaries. On one hand, generics typically offer lower prices than branded therapies. On the other hand, if a negotiated brand-name drug becomes competitively priced, some plans may continue to cover it preferentially—especially if therapeutic familiarity or limited supply of the generic exists. Pharmacists should be aware that all negotiated drugs must be included on Medicare Part D formularies across all strengths and formulations, ensuring continued access regardless of payer preference.²⁰

With more biosimilars and generics expected in the years ahead, the intersection of patent expirations and IRA price negotiations will increasingly influence prescribing trends, formulary decisions, and patient counseling. Pharmacists will play a key role in evaluating cost-effectiveness, understanding plan-specific coverage, and guiding patients through the implications of switching or staying on branded therapies.

Conclusion

The years ahead will test the adaptability and clinical leadership of pharmacists as many familiar brand-name therapies lose exclusivity and give rise to generics and biosimilars. While these changes hold promise for cost savings and broader access, they also introduce layers of complexity involving substitution rules, patient expectations, and shifting payer strategies. Pharmacists must remain vigilant, staying abreast of both regulatory developments and evolving clinical evidence. By proactively managing these transitions, community pharmacists can ensure continuity of care, optimize therapeutic outcomes, and reinforce their essential role in the medication-use process amid a rapidly transforming pharmaceutical landscape.

REFERENCES

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2. Brilinta [package insert]. AstraZeneca; November 2024. Accessed April 16, 2025. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/565ceafd-fbe3-4573-9c39-19280af566ec/565ceafd-fbe3-4573-9c39-19280af566ec_viewable_rendition__v.pdf

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8. Investor Statement on Eliquis Revenue Under IRA. Bristol Myers Squibb. Accessed April 16, 2025. https://www.bms.com/investor-statement-on-eliquis-revenue-under-ira.html

9. Jeremias S. Welcome Wezlana: the first Stelara biosimilar to launch in the US. The Center for Biosimilars. January 31, 2025. Accessed April 16, 2025. https://www.centerforbiosimilars.com/view/welcome-wezlana-the-first-stelara-biosimilar-to-launch-in-the-us

10. Jeremias S. FDA approvals Steqeyma: the seventh Stelara biosimilar. The Center for Biosimilars. December 18, 2024. Accessed April 16, 2025. https://www.centerforbiosimilars.com/view/fda-approves-steqeyma-the-seventh-stelara-biosimilar

11. FDA approves Yesintek, sixth Stelara biosimilar; launch slated for February. Healio. December 2, 2024. Accessed April 16, 2025. https://www.healio.com/news/rheumatology/20241202/fda-approves-yesintek-sixth-stelara-biosimilar-launch-slated-for-february

12. FDA Approves Third Stelara Biosimilar. Managed Healthcare Executive. Updated July 1, 2024. Accessed April 16, 2025. https://www.managedhealthcareexecutive.com/view/fda-approves-third-stelara-biosimilar

13. Humphreys S. Understanding interchangeable biosimilars at the federal and state levels. AJMC. 2023;29(7):SP545-SP548. doi:10.37765/ajmc.2023.89419

14. FDA updates guidance on interchangeability. News release. FDA. Updated June 20, 2024. Accessed April 16, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-guidance-interchangeability

15. Biosimilars of denosumab. Generics and Biosimilars Initiative. Updated December 11, 2020. Accessed April 16, 2025. https://gabionline.net/biosimilars/general/Biosimilars-of-denosumab

16. Approval Alert: Samsung Bioepis’ Denosumab Biosimilars Second to be Approved in US. News release. Pearce IP. February 13, 2025. Accessed April 16, 2025. https://www.pearceip.law/2025/02/13/approval-alert-samsung-bioepis-denosumab-biosimilars-second-to-be-approved-in-us/

17. Sandoz reaches agreement with Amgen resolving all patent litigation related to its US denosumab biosimilars. News release. Sandoz. April 30, 2024. Accessed April 16, 2025. https://www.investors.sandoz.com/sandoz-reaches-agreement-amgen-resolving-all-patent-litigation-related-its-us-denosumab-biosimilars/

18. Medicare Drug Price Negotiation. Centers for Medicare and Medicaid Services. Updated March 17, 2025. Accessed April 16, 2025. https://www.cms.gov/inflation-reduction-act-and-medicare/medicare-drug-price-negotiation

19. Cubanski J. FAQs about the Inflation Reduction Act’s Medicare Drug Price Negotiation Program. KFF. January 23, 2025. Accessed April 16, 2025. https://www.kff.org/medicare/issue-brief/faqs-about-the-inflation-reduction-acts-medicare-drug-price-negotiation-program/

20. Medicare Drug Price Negotiation Program: Final Guidance, Implementation of Sections 1191-1198 of the Social Security Act for Initial Price Applicability Year 2027 and Manufacturer Effectuation of the Maximum Fair Price in 2026 and 2027. Email from Meena Seshamani, CMS Deputy Administrator and Director of the Center for Medicare. October 2, 2024. Accessed April 16, 2025. https://www.cms.gov/files/document/medicare-drug-price-negotiation-final-guidance-ipay-2027-and-manufacturer-effectuation-mfp-2026-2027.pdf