Nilotinib Hydrochloride

iStock, photoschmidt Merck’s Keytruda may be the most talked about drug facing loss of exclusivity but it’s far from the only one, as several of the industry’s top-performers are losing key market protections. Some companies are more prepared than others. Biopharma is being battered by patent headwinds that are the strongest they’ve been in nearly 15 years. That’s according to a report last month from analyst firm William Blair, which estimates that from 2023 through the end of 2025, nearly 50 products will have lost patent protections—in turn eroding the aggregate sales of these drugs from $162.8 billion in 2025 to just $67 billion in 2029. “We believe the biggest headwind to large pharma revenue growth over the next five years is loss of exclusivity,” William Blair analysts wrote in the report. The patent cliff is exactly that: a cliff. Take AbbVie’s Humira, for instance. The immunology juggernaut is one of the most high-pro to go off patent in recent years after topping the list of pharma’s highest selling drugs for much of its blissful patent-protected period. AbbVie recorded sales of $21.24 billion in 2022. The year after, sales were $14.04 billion and last year just $8.99 billion. To patch the hole, AbbVie has leaned on its new immunology stars, Skyrizi and Rinvoq, which brought in $11.72 billion and $5.97 billion globally in 2024, respectively. Five industry powerhouses will see the same challenge in the coming years, as potential biosimilar and generic competition threaten sales. According to William Blair, the loss will affect assets that accounted for more than 30% of the collective revenues from Bristol Myers Squibb, Pfizer, AstraZeneca, Novartis and Regeneron in 2024. In this article, BioSpace looks at five pharma players—and one honorable mention—facing the greatest loss of sales in the coming years and how they’re planning to replace the revenue. Merck Set to Lose Exclusivity for Keytruda, Seminal PD-1 Inhibitor Assets at risk : Lenvima (2025), Januvia and Janumet (2026), Lynparza (2027), Gardasil/Gardasil 9 (2028) and Keytruda (2028) Perhaps the most talked about patent cliff belongs to Merck’s blockbuster cancer therapy Keytruda, one of the industry’s highest-earning assets with more than $29 billion in sales last year. Keytruda faces a key patent expiry in 2028. To help shore up the drug’s sales, Merck is gearing up for regulatory discussions about its subcutaneous formulation of the PD-1 blocker. If successful, the product’s launch could lessen the grade of the patent cliff the company inevitably faces. Aside from subcutaneous Keytruda, Merck is leaning on its pulmonary hypertension therapy Winrevair, which according to William Blair will be the pharma’s “main driver of growth,” expecting $4.9 billion in sales in 2029. Other Merck assets set to encounter patent headwinds in the coming years include the cancer drug Lenvima later this year, Gardasil/Gardasil 9 in 2028, the diabetes drugs Januvia and Janumet in 2026 and the cancer therapy Lynparza in 2027. Bristol Myers Squibb Cuts Costs and Jobs in Face of Three Impending Cliffs Assets at risk : Yervoy (2025), Eliquis (2026) and Opdivo (2028) As in the case of Regeneron, BMS is set to lose key protections for one its most valuable assets. Eliquis, an anticoagulant for the prevention of stroke, made over $13 billion in 2024. Ahead of the loss of exclusivity in 2026, several generics have already secured the FDA’s approval. These include copycats from Mylan Pharmaceuticals and Micro Labs Limited, which the FDA greenlit in December 2019 . BMS and its partner Pfizer have put up a strong legal effort to stall these generics, securing a critical court win in August 2020 that would let them keep the market to themselves until 2026. Still, the pressure is on for BMS to find alternative sources of revenue, especially because its cancer therapy Yervoy faces loss of exclusivity even sooner—this year. Yervoy brought in $2.5 billion for the pharma in 2024. According to William Blair, BMS is unprepared for the cliffs its facing, “despite several recent notable acquisitions, there is not much to get excited about in Bristol Myers’ late-stage pipeline,” the firm wrote. BMS’s most standout asset is the PD-1 blocker Opdivo, which likewise faces key expiries in 2028, though a recently approved subcutaneous formulation could help buoy growth through this point and beyond. Instead of beefing up its pipeline, BMS has chosen to weather the storm with cost-cuts. In April 2024, the pharma kicked off a sweeping realignment program —which includes around 2,200 layoffs—with an eye toward saving up to $1.5 billion through 2025. In its full-year 2024 business report earlier this month, the company tacked another $2 billion to the cost-cutting goal, which it hopes to realize through 2027. Eliquis Tops Pfizer’s List of Patent Problems Asset at risk : Prevnar (2026), Ibrance (2027), Xtandi (2027) and Eliquis (2028) Eliquis’ loss of exclusivity could be even more painful for Pfizer , the prospects of which William Blair called “bleak” in its report. In 2024, Eliquis emerged as Pfizer’s top-performing asset, growing 10% year-on-year operationally to bring in $7.4 billion . But the product faces loss of exclusivity in April 2028, with several generics waiting to eat into its sales. Compounding the company’s revenue problem is the fact that Eliquis was named among the first 10 drugs subject to price negotiations with the Centers for Medicare & Medicaid Services (CMS) prescribed by the Inflation Reduction Act (IRA), with the discounted negotiated price to go into effect in 2026. Pfizer has several other assets that are set to lose key patent protections in the coming years, too, including the pneumonia shot Prevnar in 2026 and the cancer drugs Ibrance and Xtandi, both in 2027. Erosion in sales is just one of Pfizer’s problems, which also include an activist investor jockeying for control and an unreliable COVID-19 market dynamics. There’s also what William Blair called an “underwhelming legacy pipeline.” Seemingly aware of its precarious position, Pfizer sought to shore up its bottom line with an aggressive and sweeping cost-cutting measure. The savings program announced in October 2023 was designed to help the company lower its spend by $3.5 billion last year, while a more recent round in May 2024 set a $1.7 billion savings target by the end of 2027. Aside from cost-cuts, the pharma is also banking on several 2025 catalysts—including up to four regulatory decisions—that could position the pharma for better growth in coming years, according to its fourth-quarter business report . Commercially, Pfizer is leaning heavily on its antibody-drug conjugate Padcev, which CEO Albert Bourla told investors was “an important growth driver.” The company is expecting additional data for Padcev later this year that could open a path for approval in muscle-invasive bladder cancer. If approved, that indication “would nearly triple the total addressable patients in the U.S.,” Bourla said. AstraZeneca’s Plan for Reaching $80B in Revenue Despite Expiries Asset at risk : Farxiga (2025), Soliris (2025) In May 2024, AstraZeneca unveiled an ambitious plan to deliver $80 billion in total annual revenue by 2030—a goal that could be crippled when Farxiga loses key patent protections later this year. In 2024, the drug brought in $7.7 billion , corresponding to 31% year-on-year growth at constant currencies. Soliris, a key rare disease asset that brought in nearly $2.6 billion in 2024, is also facing loss of exclusivity and is expected to face biosimilar challenge this year. Still, the pharma appears well-positioned to hit its 2030 target. As per William Blair, AstraZeneca has done a “commendable job” of building out its product portfolio, particularly in the oncology space. Enhertu, a Daiichi Sankyo-partnered antibody-drug conjugate (ADC), recently won broad approval in breast cancer. Enhertu will retain crucial patent protections past 2030, according to William Blair. Other cancer standouts include Tagrisso and Imfinzi, which respectively made $6.58 billion and $4.72 billion in 2024. AstraZeneca also boasts its clinical pipeline, which could bear fruit in the near-future. In a media call ahead for the pharma’s fourth-quarter earnings report, Chief Finance Officer Aradhana Sarin called 2025 an “unprecedented catalyst-rich period” for AstraZeneca. In particular, the company is awaiting key readouts for several of its products, including not only Enhertu and Imfinzi but also the recently approved Datroway and asthma treatment Fasenra. AstraZeneca is also expecting crucial data for new assets such as camizestrant for different cancers and baxdrostat for hypertension. “The value of our pipeline has been increasing, and now we have more than 90 late-stage studies underway, with an average peak-year revenue potential of over $1 billion,” Sarin said. Novartis Struggles to Maintain Entresto’s Exclusivity Assets at risk : Entresto (2025), Xolair (2025), Jakafi (2026), Cosentyx (2029) and Tafinlar (2030) Novartis ’ patent problems escalated in 2024. The heart failure drug Entresto, which made $7.8 billion last year, is set to lose market exclusivity in July 2025 . The pharma started efforts to guard its place in the market as early as September 2022, when it filed a citizen Pptition to the FDA asking the regulator not to approve drug applications referencing Entresto and specific patents related to it. But last July, the FDA denied the petition, noting that it is possible for generic drugs to sidestep Entresto’s patents with labeling tweaks. The same month, the FDA signed off on MSN Pharmaceuticals’ generic version of Entresto. Those decisions have since opened a legal saga for Novartis, which most recently secured a last-minute stay against MSN’s copycat, preventing its market entry while the pharma’s patent complaint remains open. In its fourth-quarter and full-year 2024 earnings call last month, company executives expressed confidence that Novartis would be able to smoothly weather Entresto’s loss of exclusivity in mid-2025. The company expects to “secure pediatric exclusivity” for Entresto, which could potentially help soften the blow of generics this year, CEO Vas Narasimhan said during the call. Aside from the heart failure drug, Novartis is also facing down patent expirations for Xolair in 2025, Jakafi in 2026, Cosentyx in 2029 and Tafinlar in 2030. Ilaris, indicated for auto-inflammatory diseases, lost key protections last year, while chronic myeloid leukemia drug Tasigna became open to generic erosion in 2023. Much of Novartis’ resilience through the patent expiries will come from fiscal discipline, Chief Financial Officer Harry Kirsch explained during the call. Honorable Mention: Regeneron’s High-Dose Eylea Not Making Up for LOE Asset at risk : Eylea (2024) Regeneron is already in the throes of a major patent expiry for its blockbuster eye disease drug Eylea, which in 2024 was the pharma’s top-performing asset with $5.97 billion in sales in the U.S. But last May, the company lost key protections for the drug, thereby opening it up to considerable copycat competition. And of these, there are several. The same month Eylea went off patent, the FDA signed off on two interchangeable biosimilars, Biocon Biologics’ Yesafili and Samsung Bioepis and Biogen’s Opuviz. A few months later, Novartis spinoff Sandoz also won the regulator’s go-ahead for its own biosimilar called Enzeevu. To help protect Eylea’s place in the market, Regeneron has taken many of its competitors to court. In December 2023, the pharma sued Samsung Bio for alleged patent infringement. Regeneron also has a case against Sandoz, seeking to block the generics developer from marketing its biosimilar. The pharma has also developed a high-dose (HD) version of Eylea to keep the product’s competitive edge. The product earned the FDA greenlight in August 2023, but uptake has been slow. In the fourth quarter of 2024, Eylea HD’s sales came in at $305 million, below analyst expectations of $336 million. In the pharma’s earnings call, CEO Leonard Schleifer urged investors to “look beyond” its Eylea franchise, noting that “our strategy is not to be solely dependent on any one thing.” In 2025, Regeneron is looking forward to the launch of its anti-IL-4/IL-13 antibody Dupixent in chronic obstructive pulmonary disease, as well as several key data readouts.

In the MOTION Phase 3 study, ROMVIMZA met primary endpoint of improved objective response rate (ORR) compared to placebo and all key secondary endpoints with statistically significant and clinically meaningful improvements in quality-of-life measures, and demonstrated well-tolerated safety profile OSAKA, Japan & WALTHAM, MA, USA I February 14, 2025 I Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; “Ono”) announced that the U.S. Food and Drug Administration (FDA) has approved ROMVIMZA™ (vimseltinib), a kinase inhibitor, for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity. The FDA previously granted Fast Track designation and Priority Review for ROMVIMZA, which was developed by Deciphera Pharmaceuticals, Inc. (“Deciphera”), a wholly owned subsidiary of Ono. “The approval of ROMVIMZA provides a new, much-needed, well-tolerated, and effective treatment option for people suffering from TGCT,” said Hans Gelderblom, M.D., Ph.D., Chair of the Department of Medical Oncology at Leiden University Medical Center. “TGCT adversely affects the lives of patients, causing significant pain, limited mobility, and stiffness. The MOTION Phase 3 study demonstrated ROMVIMZA’s ability to shrink tumors along with being the first well-tolerated agent to demonstrate significant improvement in a number of other important quality-of-life measures without any observed liver injury as seen with other approved TGCT treatment. ROMVIMZA is a differentiated treatment that has the potential to address the significant unmet needs of the TGCT community.” “The FDA approval of ROMVIMZA for TGCT is a crucial advancement for the TGCT community and we believe ROMVIMZA has the potential to become the new standard of care for people with TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity. This is also an important milestone for our organization, as it is the second approved therapy discovered using Deciphera’s proprietary switch-control kinase inhibitor platform,” said Ryota Udagawa, President and Chief Executive Officer of Deciphera Pharmaceuticals. “I’d like to extend my gratitude to the patients, families, caregivers, and healthcare providers who contributed to the success in ROMVIMZA’s clinical studies. Their commitment, along with the dedication of the Deciphera and Ono teams, enabled us to advance this impactful new treatment, which we look forward to delivering to patients.” TGCT is a rare, non-malignant tumor that forms within or near joints. TGCT arises from the dysregulation of the CSF1 gene, resulting in an overproduction of CSF1. If left untreated or if the tumor repeatedly recurs, it can lead to damage and degeneration in the affected joint and surrounding tissues, potentially causing significant disability. The FDA approval was based on the efficacy and safety results from the pivotal Phase 3 MOTION study of ROMVIMZA in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed), compared to placebo, as well as the Phase 1/2 study of ROMVIMZA. In MOTION, ROMVIMZA demonstrated a statistically significant and clinically meaningful ORR at Week 25 in the intent-to-treat (ITT) population, as assessed by blinded independent radiologic review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo (40% in ROMVIMZA arm vs 0% in placebo arm, p <0.0001). The primary endpoint was supported by statistically significant and clinically meaningful improvements in active range of motion, patient-reported physical functioning, and patient-reported pain observed in the vimseltinib arm compared to the placebo arm at week 25. The safety profile of ROMVIMZA is manageable and consistent with results previously disclosed in the Phase 1/2 clinical trial. Deciphera Pharmaceuticals plans to make ROMVIMZA commercially available in the U.S. next week. Learn more at www.ROMVIMZA.com . In July of 2024, the Company announced the marketing authorization application (MAA) for ROMVIMZA for the treatment of patients with TGCT was accepted and is under review by the European Medicines Agency (EMA). Deciphera is committed to supporting TGCT patients and providers in navigating coverage and access to ROMVIMZA. As part of that commitment, Deciphera AccessPoint TM , a patient support program, is available to provide comprehensive access and financial assistance programs for eligible patients. For more information, visit DecipheraAccessPoint.com or call 1-833-4DACCES (1-833-432-2237), Monday-Friday, 8:00 AM to 8:00 PM Eastern Time (ET). About MOTION Study The MOTION study is a two-part, randomized, double-blind, placebo-controlled Phase 3 clinical study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). The primary endpoint of the study is an objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by blinded independent radiologic review (IRR) per using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo. The secondary endpoints include ORR per tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain, all assessed at Week 25. This study consists of two Parts. In Part 1, patients were randomized to receive either vimseltinib or placebo for 24 weeks. In Part 2, patients randomized to placebo in Part 1 have the option to receive vimseltinib, and all patients receive vimseltinib for a long-term period in an open-label setting. ROMVIMZA (vimseltinib) capsules INDICATIONS AND USAGE ROMVIMZA is indicated for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hepatotoxicity Embryo-Fetal Toxicity: Allergic Reactions to FD&C Yellow No.5 (Tartrazine) and No. 6 (Sunset Yellow FCF): Increased Creatinine without Affecting Renal Function: Adverse Reactions: The most common (≥20%) adverse reactions, including laboratory abnormalities that occurred in patients receiving ROMVIMZA were increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT. Drug Interactions: Lactation: Advise females not to breastfeed during treatment with ROMVIMZA. Please see the accompanying full Prescribing Information . About Tenosynovial Giant Cell Tumor (TGCT) TGCT is a rare disease caused by a translocation in colony-stimulating factor 1 (CSF1) gene resulting in overexpression of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion. TGCT is a rare, non-malignant tumor that develops inside or near joints. TGCT is caused by dysregulation of the CSF1 gene leading to overproduction of CSF1. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. Although non-malignant, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients, surgical resection will potentially cause worsening functional limitation or severe morbidity, systemic treatment options are limited and a new therapeutic option for TGCT is needed. About Deciphera Pharmaceuticals Inc. (As of June 11, 2024, Deciphera became a member of Ono Pharmaceutical Co., Ltd.) Deciphera is a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer. We are leveraging our proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology to develop a broad portfolio of innovative medicines. In addition to advancing multiple product candidates from our platform in clinical studies, QINLOCK ® (ripretinib) is Deciphera’s switch-control inhibitor approved in many countries including the European Union and the United States for the treatment of fourth-line gastrointestinal stromal tumor (GIST). ROMVIMZA™ (vimseltinib) is a kinase inhibitor approved in the United States for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity. For more information, visit www.deciphera.com and follow us on LinkedIn and Twitter (@Deciphera). SOURCE: Ono Pharmaceutical