Merck KGaA BTK inhibitor beats placebo in phase 2 multiple sclerosis trial

Merck kgaa
Compared to placebo, evobrutinib delivered reductions in the recently-inflamed lesions. (Image: Merck KGaA)

A phase 2a trial of Merck KGaA’s BTK inhibitor evobrutinib has hit its primary endpoint. The prospect chalked up the win by reducing gadolinium-enhancing T1 lesions by more than placebo, but Merck has yet to quantify the difference or say how it fared against rival multiple sclerosis drug Tecfidera.

Those gaps in the information released so far leave critical questions about the safety and efficacy of evobrutinib unanswered. But Merck presented the results it has seen as a positive for evobrutinib. If that interpretation stands up to scrutiny, the trial will boost a key drug in Merck’s midphase pipeline that is advancing in multiple major immunological conditions.

Investigators enrolled 267 patients with relapsing multiple sclerosis in the trial and randomized them to receive one of three doses of evobrutinib, placebo or Tecfidera for 24 weeks. After 24 weeks, patients in the placebo arm switched to the low dose of evobrutinib for the remainder of the trial.

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Merck was primarily interested in how evobrutinib performed over that initial, 24-week period. Compared to placebo, evobrutinib delivered "clinically meaningful" reductions in the recently-inflamed lesions that characterize multiple sclerosis relapses. Those declines were seen at the four time points from 12 to 24 weeks that served as the study’s primary endpoint.

Merck said the trial met its primary endpoint but made no mention of statistical significance, instead calling the reductions “clinically meaningful,” and is yet to provide p values. Other missing pieces of the data include the quantification of evobrutinib’s effect on lesions, a comparison between Merck’s experimental drug and Biogen’s Tecfidera and any insights into adverse events.

Those gaps leave preclude critical assessments of Merck’s interpretation of the results.

“We are encouraged by these early positive results of evobrutinib in relapsing MS," Luciano Rossetti, head of global R&D at Merck’s biopharma business, said in a statement. "The trial will continue so as to further inform our clinical development strategy for evobrutinib in MS."

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The early look at the data is one of a series of upcoming readouts that will dictate whether Merck’s excitement about the potential of evobrutinib is justified. A phase 2 trial of the BTK inhibitor in systemic lupus erythematosus is due to deliver data late next year. And Merck is also testing the drug in a phase 2b rheumatoid arthritis trial. 

Collectively, the trials will dictate whether evobrutinib advances into a multi-indication phase 3 trial program or withers before reaching that stage. In September, Merck said it was considering strategic partnerships and financing to realize the full potential of evobrutinib.

Merck is a notable proponent of the use of BTK inhibitors to treat immunological disorders but it is far from the only firm to pick up on research linking such drugs to effects on immune cell signalling. Principia Biopharma has built its clinical-phase pipeline upon the idea while snagging a $40 million upfront from Sanofi for an earlier-stage asset.