Merck’s plans to expand the reach of its blockbuster cancer drug Keytruda with a new subcutaneous (injectable) formulation are encountering a significant obstacle. Halozyme Therapeutics has accused Merck of infringing on its patents related to the hyaluronidase enzyme, which is critical for drug delivery. This dispute could jeopardize Merck’s strategy to maintain Keytruda’s market dominance as the patents for its intravenous (IV) version approach expiration.
Legal Battle Over Hyaluronidase Enzyme Patents
Halozyme claims that Merck’s new injectable version of Keytruda infringes its patented technology for hyaluronidase enzymes, which are used to facilitate the delivery of drugs through subcutaneous injections. This challenge threatens Merck’s efforts to transition Keytruda into an injectable format, potentially extending its market life after the expiration of its IV patents. In response, Merck has vehemently disputed the validity of Halozyme’s patents, signaling an impending and high-stakes legal showdown that could significantly impact the future of its cancer treatment.
Merck stated, “We strongly believe that any Halozyme patents attempting to cover this variant are invalid,” and confirmed it has already filed petitions with the U.S. Patent Office to challenge the patents’ legitimacy. Meanwhile, Merck continues clinical trials for the injectable version of Keytruda and anticipates its launch by early 2026.
The injectable form of Keytruda has shown promising results in clinical trials, with researchers finding it to be as effective as the traditional IV version, which generated $29.5 billion in sales in 2024. To bring the injectable version to market, Merck has partnered with South Korea-based biopharmaceutical company Alteogen, which has developed a variant of the hyaluronidase enzyme that enables large-volume subcutaneous administration.
Halozyme’s Role and Broader Industry Implications
Halozyme, which competes with Alteogen, also develops hyaluronidase enzyme-based drug delivery systems for injectable treatments. The company’s technology is already used in products from major pharmaceutical players like Roche, Johnson & Johnson, and Pfizer. While Halozyme prefers to establish licensing agreements for its intellectual property, it has not publicly commented on the potential for litigation with Merck.
The ongoing legal battle could have broader implications for the pharmaceutical industry’s use of hyaluronidase enzymes in drug delivery. If Merck is forced to halt its use of Halozyme’s technology, it could reshape the landscape of injectable treatments for a variety of drugs, not just Keytruda.
FDA Review for Keytruda’s New Indication
In addition to the ongoing patent dispute, Merck announced that the FDA has accepted a supplemental Biologics License Application (sBLA) for Keytruda, seeking approval for its use as a neoadjuvant treatment for patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The application is supported by Phase 3 KEYNOTE-689 trial data, which showed significant improvements in event-free survival (EFS) and major pathological response (mPR) compared to standard adjuvant therapy alone.
The FDA has set a target action date of June 23, 2025, for this application, under the Prescription Drug User Fee Act (PDUFA). The review also falls under the FDA’s Project Orbis, which facilitates simultaneous reviews of oncology drugs across multiple countries, including Israel, Canada, Australia, and others.
Merck’s Expanding Keytruda Portfolio
Merck is also seeking to expand the use of Keytruda under Project Orbis, with a focus on reducing recurrence and disease progression in earlier stages of LA-HNSCC. Dr. Marjorie Green, Merck’s head of oncology clinical development, emphasized the need for new treatment options for LA-HNSCC, given that current standards have not changed for over 20 years. “We look forward to working with the FDA to potentially bring Keytruda to these patients as soon as possible,” said Green.
Keytruda is already approved for use in metastatic and unresectable recurrent HNSCC in combination with other therapies, and Merck hopes the new indication will provide additional treatment options for patients with earlier-stage disease.
The Competitive Landscape
This legal dispute underscores the competitive environment surrounding hyaluronidase enzyme-based drug delivery technologies. While Merck has teamed up with Alteogen for its injectable Keytruda, Halozyme’s technology is used by other major pharmaceutical companies, and the outcome of the dispute could have far-reaching effects on the future of injectable drug delivery systems.
As Merck fights to extend the market life of Keytruda, the legal and regulatory developments will play a crucial role in determining the drug’s trajectory in the years to come.
