Merck KGaA Halts BTK Inhibitor Development Post-MS Trial Failures

Merck KGaA discontinued the development of their BTK inhibitor, evobrutinib, intended for treating multiple sclerosis (MS), as noted in their fourth quarter 2023 financial results. CEO Belén Garijo confirmed the official termination of the program during an investor call.

In December 2023, Merck KGaA announced that two Phase III trials assessing the safety and efficacy of evobrutinib did not achieve their primary endpoints, which aimed at reducing the annualized relapse rates in MS patients. Despite this setback, Garijo remained optimistic about the company's standing in the healthcare sector, expressing confidence in its overall strategic position.

The discontinuation of the evobrutinib program incurred a cost of €95 million ($103.8 million), attributed to a one-time payment. Additionally, Garijo highlighted that there will be no prelaunch expenses for evobrutinib, unlike the previous year.

This was not the first challenge Merck KGaA faced with their BTK inhibitor. In April 2023, the FDA imposed a clinical hold on the Phase III trial after two patients exhibited liver injury symptoms. Consequently, new patient enrollment was halted, and dosing for participants who had been on treatment for less than 70 days was discontinued.

The class of BTK inhibitors, including Merck KGaA’s evobrutinib, has faced several issues. Before Merck's Phase III failures, Roche’s BTK inhibitor for MS also encountered a clinical hold by the FDA due to potential liver injury cases. In particular, two patients in Roche’s Phase III study of fenebrutinib exhibited elevated hepatic transaminase levels post-dosing.

Other BTK inhibitors have similarly faced partial clinical holds from the FDA.

While dealing with these hurdles, Merck KGaA has explored other areas in their research initiatives. In January 2023, the company broadened its colorectal cancer treatment capabilities by securing two assets from Inspirna for an upfront payment of $45 million. Additionally, on a recent Monday, Merck KGaA entered into a research collaboration with C4 Therapeutics, investing $16 million upfront and potentially over $740 million in milestone payments to discover two targeted protein degraders aimed at addressing crucial oncogenic proteins.