Merck & Co. has announced positive results from a Phase 3 clinical trial evaluating a subcutaneous formulation of its blockbuster cancer immunotherapy, Keytruda (pembrolizumab). The trial demonstrated that the under-the-skin injection achieved comparable drug levels in the blood as the currently available intravenous (IV) formulation in patients with non-small cell lung cancer (NSCLC).
The study, designed to assess the pharmacokinetics, safety, and efficacy of the subcutaneous Keytruda, met its primary endpoint by showing that blood concentrations of the drug were similar between the two formulations at periodic time checks, including just before the next dose administration. Merck stated that secondary measures of safety and efficacy were "generally consistent" between the subcutaneous and IV versions.
The development of a subcutaneous formulation is crucial for Merck as it faces the impending patent expiration of IV Keytruda in the U.S. in 2028. A subcutaneous version, protected by new patents, offers a more convenient administration route for patients, potentially sustaining revenue from the drug, which generated nearly $22 billion in sales in the first nine months of 2024.
The subcutaneous Keytruda combines pembrolizumab with an enzyme developed by Alteogen, a South Korean biotech company, to enhance absorption and dispersion in the body. The Phase 3 trial specifically enrolled patients with NSCLC, the largest indication for Keytruda, and administered both formulations in combination with chemotherapy.
Other pharmaceutical companies are also developing subcutaneous versions of their immunotherapies. Roche's subcutaneous Tecentriq has already received FDA approval, and Bristol Myers Squibb awaits an FDA decision on its subcutaneous Opdivo. These subcutaneous formulations utilize an enzyme developed by Halozyme.
While Keytruda holds a dominant position in the front-line NSCLC setting, the subcutaneous formulation aims to maintain its market share against potential biosimilar competition following the 2028 patent expiration. Several biosimilar manufacturers, including Sandoz, Samsung Bioepis, Amgen, and Celltrion, are actively developing their own versions of pembrolizumab.
