Merck, Halozyme dig in for injectable Keytruda patent fight

Both Merck & Co. and Halozyme are holding their ground in a freshly unveiled patent dispute surrounding the New Jersey pharma’s under-the-skin version of its blockbuster cancer drug Keytruda.

Halozyme alleges that Merck’s new formulation of Keytruda infringes on its technology involving the use of a protein called human hyaluronidase to enable subcutaneous delivery of drugs.

The California-based company is trying to get Merck on board with a licensing arrangement, but it’s prepared to resort to lawsuits if that attempt fails, Halozyme CEO Helen Torley said Wednesday at the TD Cowen 45th Annual Healthcare Conference.

For its part, Merck has filed petitions to invalidate certain Halozyme patents in dispute, a company spokesperson told Fierce Pharma.

Both companies are not flinching—at least publicly.

“We can come at this from a very strong [position of] strength,” Torley said at the TD Cowen event.

“We strongly believe any Halozyme patents that attempt to cover this variant are invalid,” the Merck spokesperson said, adding the company has “confidence in our legal position.”

Subcutaneous Keytruda represents Merck’s solution to expand access to the popular PD-1 inhibitor and preserve some of its revenue as the original intravenous infusion version is expected to lose patent protection in 2028.

In an accelerated timeline, Merck aims to launch the new formulation in 2025, CEO Rob Davis said in January at the J.P. Morgan Healthcare Conference. Detailed clinical data in non-small cell lung cancer, unveiled in November, showed that subcutaneous Keytruda matched up to its IV form on two pharmacokinetic endpoints.

Merck sees a significant market opportunity for subcutaneous Keytruda. The company has projected that the biggest demand for a subcutaneous formulation will come from patients with early-stage cancers, who often receive PD-1/L1 inhibitors like Keytruda as a single agent, or in indications where the drug is combined with oral therapies.

By Merck’s estimate, those types of uses will together represent about 50% of the total Keytruda patient population by 2028.

To develop the new product, Merck licensed a hyaluronidase variant from Alteogen. Called ALT-B4, the variant was independently developed by Alteogen scientists, and its sequence is not disclosed in any Halozyme patent, the Merck spokesperson noted.

Halozyme’s claim stems from its Mdase group of modified human hyaluronidases, which the company publicized in October. Halozyme came up with its Mdase tech to sign more partners who may not be able to tap into the company’s well-established Enhanze subcutaneous drug delivery platform thanks to existing exclusive licensing pacts.

The Mdase portfolio includes about 100 patents with protection extending into 2032 in Europe and 2034 in the U.S., according to Halozyme.

“Halozyme has been working on inventing the hyaluronidases for more than 20 years. That really does give us a very strong position as a group who were making claims and getting patents filed,” Torley said.

“Because of that wealth of experience and the breadth of patents […] that’s what really gives us the confidence that we are going to prevail, and that the other companies who are developing modified hyaluronidases are infringing,” she continued. “Nobody was working in this field for the many years we were getting these 100 patents issued.”

Halozyme made a name in the biopharma world with Enhanze, which has been used in multiple products. One such drug is Bristol Myers Squibb’s rival subcutaneous PD-1 inhibitor, Opdivo Qvantig, which won an FDA approval at the end of 2024. Enhanze and Mdase are separate bodies of intellectual property and do not affect each other, Halozyme’s general counsel Mark Snyder stressed during the TD Cowen event.

According to Snyder, Merck has filed with the U.S. Patent and Trademark Office seeking an administrative review of seven Mdase patents. The agency will likely decide whether to take up the case by June. Halozyme believes that the case won’t move forward because the patents are “not subject to challenge in the way that Merck” has presented its case, Snyder said at the TD Cowen event.

For now, Halozyme’s hope is that the two sides can shake hands on a licensing pact. Referencing past deals on Enhanze, Torley said a potential Mdase deal would take a milestones-royalties structure, with royalty rates in a range of 3% to 7%, which Torley said is “a very reasonable starting place.”

If that turns out to be a dead end, Snyder said Halozyme is prepared to seek an injunction in a lawsuit to prevent Merck from selling subcutaneous Keytruda.