Merck posts early clinical data on subcutaneous Keytruda, setting stage for further studies 

Merck has presented early clinical data on subcutaneous formulations of its blockbuster checkpoint inhibitor Keytruda. The data drop is an early step in an ongoing effort to reformulate Keytruda ahead of the anticipated expiration of U.S. patents in 2028.

Keytruda and rival checkpoint inhibitors are currently given intravenously. However, as in other parts of the biologics industry, there is some interest in moving to subcutaneous formulations that reduce the burden on patients. Pfizer is a big proponent of the approach, having taken subcutaneous PD-1 drug sasanlimab into phase 3 late in 2019, but market leader Merck is also active. 

Merck began a phase 1 trial to test two different concentrations of the pembrolizumab antibody in subcutaneous formulations in melanoma patients in 2018. The researchers presented data from the study at the American Association for Cancer Research Annual Meeting.

Investigators randomized advanced melanoma patients to take a 200-mg intravenous dose and two 285-mg subcutaneous doses—one of each concentration—in a crossover design during the first three treatment cycles. The study gathered pembrolizumab concentration data from 31 people.

Merck said the pharmacokinetics of the two subcutaneous formulations were similar. The estimated bioavailability was 64%. The figure is consistent with the bioavailability data for other subcutaneously administered antibodies, which the researchers said range from 50% to 85%. Pfizer linked sasanlimab to a subcutaneous bioavailability of around 60%.

Buoyed by the finding, the researchers outlined plans to assess subcutaneous formulations in other tumor types. The plans are part of a broader strategy of identifying ways of improving the benefits of Keytruda to patients and healthcare systems, which is gathering pace ahead of the loss of U.S. patent protection in 2028.

“We’ll look at different subcutaneous options. We’ll look at different co-formulation options. Each of those have different IP associated with them. Where we’re adding distinct patient and system value, we’ll pursue that IP appropriately,” Michael Nally, chief marketing officer at Merck, said at an event last month.