Merck KGaA’s highly anticipated experimental multiple sclerosis (MS) drug failed to meet its primary endpoint in two Phase 3 trials, the company announced this week.
The EVOLUTION trials found that the drug, evobrutinib, didn’t meet its primary endpoint of reducing annualized relapse rates in patients with relapsing MS compared to Sanofi’s Aubagio, a current MS treatment that was originally approved by the Food and Drug Administration in 2012.
Merck KGaA noted the overall safety and tolerability of the drug was consistent with previous trials.
“While we are very disappointed with the results, we continue to advance our strategy in healthcare with a focus on progressing our marketed portfolio and internal pipeline, complemented by external innovation, with the aim of bringing more medicines to patients, faster,” said Danny Bar-Zohar, global head of research and development and chief medical officer for the healthcare business sector at MerckKGaA, in a statement. .
The results triggered Merck KGaA’s shares to drop 14% Wednesday and opened up doubts about the potential of BTK inhibitors in treating MS and chronic inflammation, an area that has seen plenty of ambition lately.
Sanofi, Novartis and Roche’s Genentech have all sought to invest in BTK inhibitor candidates recently, but they’ve also experienced occasional setbacks.
At the end of November, the FDA placed a partial clinical hold on Genentech’s BTK inhibitor fenebrutinib due to two cases of high liver enzymes in patients enrolled in the trial. Genentech said in a statement that it would pause enrolling new patients into its Phase 3 trial in the U.S.
In April, evobrutinib faced a similar issue when the FDA paused enrollment of new patients in the Phase 3 trial due to concerns, again, about liver injury.
Merck KGaA said it would complete a full evaluation of the EVOLUTION data, but the latest results leave large question marks around the future of the BTK inhibitor space for MS, especially after evobrutinib had garnered a significant amount of anticipation and promise.
“Evobrutinib is the first drug in the novel BTKi class, which are potentially more effective at slowing disability accumulation when compared to approved therapies,” noted Sandra Teoh, senior research manager at Ipsos, in the 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.”Merck will now have to turn its attention to other pipeline assets, though it’s had a busy fall regardless – most recently completing an acquisition of preclinical biotech Caraway Therapeutics in November.
