Merck Faces Patent Battle with Halozyme Over Latest Keytruda Injection

Merck’s plan to extend Keytruda’s market dominance with a new injectable version faces a major hurdle. Halozyme Therapeutics has accused Merck of infringing its patents on a hyaluronidase enzyme used for drug delivery. The dispute threatens Merck’s strategy to maintain sales after Keytruda’s intravenous patents expire. In response, Merck is challenging the validity of Halozyme’s patents, setting the stage for a high-stakes legal battle.

Hyaluronidase Enzyme Patents Raise Questions about Injectable Keytruda Claims

Halozyme Therapeutics alleges that Merck’s new subcutaneous formulation of Keytruda infringes on its patented hyaluronidase enzyme technology for drug delivery. The claim threatens Merck’s efforts to transition Keytruda to an injectable format as patents for the intravenous version near expiration. Merck, however, disputes the validity of Halozyme’s patents, signaling an intense legal battle that could shape the future of its blockbuster cancer drug.

Merck told Reuters, “We strongly believe that any Halozyme patents attempting to cover this variant are invalid,” adding that it has already filed invalidity petitions with the U.S. patent office. In November, researchers found Merck’s injectable Keytruda to be equally effective as the IV version, which generated $29.5 billion in sales in 2024.

Merck has partnered with South Korea-based biopharmaceutical firm Alteogen to utilize a hyaluronidase enzyme variant, enabling large-volume subcutaneous (under-the-skin) drug administration.

Meanwhile, Halozyme, a competitor of Alteogen, also employs hyaluronidase enzymes for injectable drug development, supporting treatments from Roche, Johnson & Johnson, and Pfizer, among others. Halozyme prefers to establish licensing agreements with companies using its intellectual property for drug delivery but has declined to comment on potential litigation. Merck is still conducting clinical trials for the injectable Keytruda and anticipates launching it by early 2026. 

FDA Approves Keytruda for Priority BLA Review

Merck announced that the Food and Drug Administration (FDA) has accepted for priority review a supplemental Biologics License Application (sBLA) for Keytruda (pembrolizumab). The application seeks approval for its anti-programmed cell death ligand 1 (anti-PD-1) therapy for patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The proposed regimen includes Keytruda as a neoadjuvant treatment, followed by adjuvant therapy with standard radiotherapy (with or without cisplatin) and continued as a single agent. 

The FDA has set a target action date of June 23, 2025, under the Prescription Drug User Fee Act (PDUFA). The sBLA is supported by Phase 3 KEYNOTE-689 trial data (NCT03765918), which showed statistically significant improvements in event-free survival (EFS) and major pathological response (mPR) compared to adjuvant radiotherapy alone, with a consistent safety profile.

Merck Seeks Keytruda Expansion Under Project Orbis

The review falls under Project Orbis, an FDA initiative for simultaneous oncology drug reviews across multiple countries, including Israel, Canada, Australia, Singapore, Brazil, and Switzerland. Dr. Marjorie Green, Merck’s head of oncology clinical development, emphasized the urgent need for new treatment options for LA-HNSCC, as current standards have remained unchanged for over two decades.

“Based on the compelling results of the KEYNOTE-689 trial, we hope to reduce the risk of recurrence and disease progression in earlier stages of disease. We look forward to working with the FDA to potentially bring Keytruda to these patients as soon as possible.” said by Green.

With this, Merck aims to reduce recurrence and disease progression at earlier stages of the disease. Regulatory agencies across multiple global markets, including the U.S., Europe, China, and Japan, have already approved Keytruda as a monotherapy and in combination therapies for metastatic or unresectable, recurrent HNSCC.

The dispute highlights the competitive landscape around hyaluronidase enzyme-based drug delivery systems, with Merck partnering with Alteogen and Halozyme working with other major pharmaceutical companies.

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Author

Steven Chung