In a setback for Merck KGaA, the company’s promising drug candidate for multiple sclerosis (MS), evobrutinib, failed to outperform an existing treatment in pivotal Phase 3 trials. The EVOLUTION trials revealed that evobrutinib did not achieve the primary goal of reducing annualized relapse rates in relapsing MS patients when compared to Sanofi’s Aubagio, a competitor approved by the FDA in 2012.
Despite the disappointing outcome, Merck KGaA highlighted that evobrutinib’s safety profile remained consistent with earlier studies. Danny Bar-Zohar, the global head of research and development and chief medical officer for Merck KGaA’s healthcare sector, expressed the company’s commitment to healthcare innovation despite the trials’ results. “We are very disappointed with the results, but we continue to advance our strategy in healthcare, focusing on our marketed portfolio and internal pipeline, complemented by external innovation, with the aim of bringing more medicines to patients, faster,” he stated.
The news of the trial results prompted a 14% drop in Merck KGaA’s shares and cast doubt on the potential of Bruton’s tyrosine kinase (BTK) inhibitors in treating MS and chronic inflammation. This drug class has recently attracted significant interest, with pharmaceutical giants such as Sanofi, Novartis, and Roche’s Genentech investing in BTK inhibitor candidates. However, the journey has not been without challenges.
For instance, Genentech’s BTK inhibitor, fenebrutinib, encountered a partial clinical hold by the FDA in November due to liver enzyme elevations in two trial participants. This led to a pause in enrolling new patients in the U.S. Phase 3 trial. Similarly, evobrutinib’s trial enrollment was temporarily halted by the FDA in April over concerns about potential liver injury.
Merck KGaA has pledged to conduct a thorough analysis of the EVOLUTION trial data. However, the results have raised significant questions about the future of BTK inhibitors in the MS treatment landscape, particularly after evobrutinib had been viewed as a highly anticipated and promising new therapy.
“The first drug in the novel BTKi class, evobrutinib, was potentially more effective at slowing disability accumulation compared to approved therapies,” said Sandra Teoh, senior research manager at Ipsos, last fall. “The Phase 3 readout anticipated later this year should clarify whether evobrutinib can compete with the big hitters in the market, the anti-CD20s.”
With evobrutinib’s future uncertain, Merck KGaA will now refocus on other assets in its pipeline. The company has been active, recently acquiring preclinical biotech Caraway Therapeutics in November.
