Merck's Subcutaneous Keytruda Shows Promise in Lung Cancer, Faces Patent Hurdle

Merck & Co.'s efforts to develop a more convenient formulation of its blockbuster cancer drug Keytruda have yielded positive results, potentially paving the way for FDA approval. However, the pharmaceutical giant faces a patent dispute that could complicate its plans for commercialization.

Subcutaneous Keytruda Matches IV Formulation in Phase 3 Trial

Merck's subcutaneous (SC) formulation of Keytruda has demonstrated noninferiority to the original intravenous (IV) version in a pivotal phase 3 trial. The study, known as 3475A-D77, evaluated both formulations in combination with chemotherapy for patients with newly diagnosed metastatic non-small cell lung cancer.

The trial met its dual primary endpoints, showing comparable blood concentration measurements between the SC and IV versions. Specifically, the SC formulation was noninferior in terms of overall drug exposure during the first cycle of treatment and steady-state trough concentration during cycle 3. The geometric mean ratios for these endpoints were 1.14 and 1.67, respectively, both exceeding the 0.8 threshold for noninferiority.

Efficacy data from the trial, while descriptive and not statistically powered for comparison, showed similar results between the two formulations. After a median follow-up of 9.6 months, the risk of disease progression or death was comparable, with a marginal 5% advantage for the IV version. Interestingly, patient survival results favored the SC formulation, showing a 19% improvement.

Convenience and Administration Benefits

The subcutaneous formulation of Keytruda offers significant advantages in terms of administration time and convenience. In the clinical trial, the median injection time for Keytruda SC was just two minutes, compared to the typical 30-minute infusion time for the IV version.

A prospective analysis revealed that patient time in the treatment chair was nearly halved with the SC injection, from 117 minutes with IV to 59 minutes with SC. This calculation excluded chemotherapy administration time. Healthcare providers also benefited, with a 46% reduction in time spent on preparation, administration, and patient monitoring for the SC version.

Marjorie Green, head of oncology global clinical development at Merck Research Laboratories, emphasized the potential impact of this development, stating, "If approved, we are excited about the potential of subcutaneous [Keytruda] to become a new meaningful treatment option that may increase access and save time needed for administration compared to IV Keytruda."

Patent Dispute with Halozyme Threatens Commercialization

While Merck aims to launch Keytruda SC this year, pending FDA approval, the company faces a significant hurdle in the form of a patent dispute with drug delivery specialist Halozyme Therapeutics. The conflict centers around the human hyaluronidase protein used in the SC formulation, which Halozyme alleges infringes its Mdase portfolio of patents.

Merck licenses the protein, called berahyaluronidase alfa, from Alteogen and has filed a petition with the U.S. Patent and Trademark Office to challenge seven of Halozyme's patents. Halozyme, for its part, has expressed interest in reaching a licensing agreement with Merck and has indicated willingness to seek an injunction to prevent commercialization if a deal cannot be reached.

This legal battle could potentially delay or complicate Merck's plans to bring the subcutaneous version of Keytruda to market, despite the positive clinical results and pending FDA decision, expected by September 23, 2025.