Merck pummelled as MS hope evobrutinib dies in phase 3

Dmitriy Gutarev

Germany’s Merck KGaA is facing a big hole in its late-stage pipeline after multiple sclerosis (MS) candidate evobrutinib missed the mark in two phase 3 trials, spelling the end of the programme and wreaking havoc with its share price.

In a statement, the drugmaker said that in the two EVOLUTION studies – evolutionRMS 1 and 2 – BTK inhibitor evobrutinib did not meet the primary objective of reducing annualised relapse rates (ARR) in patients with relapsing multiple sclerosis (RMS) when compared to oral teriflunomide.

Evobrutinib was one of a handful of drugs in the BTK inhibitor class vying to become a new oral therapy for MS and, as a frontrunner in that effort, its demise hands an advantage to rivals including Roche/Genentech’s fenebrutinib, Novartis’ remibrutinib, Sanofi’s tolebrutinib, and Biogen/InnoCare’s orelabrutinib.

It was the first BTK inhibitor to show proof-of-concept in relapsing MS in a phase 2 trial reported in 2019, reducing the cumulative number of brain lesions over time compared to placebo.

Merck said that ARR for oral teriflunomide was lower than has been seen in other recent phase 3 trials, which made it harder for evobrutinib to show an advantage, but that will be small comfort to the company as it works through the data for future publication.

“With evobrutinib, our aim was to address the significant unmet need of smouldering MS in addition to strong relapse control for people living with this condition,” commented Danny Bar-Zohar, chief medical officer for Merck’s healthcare business.

“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,” he added.

There’s little doubt that losing evobrutinib is a heavy blow, given that Merck had been predicting sales of the drug could top $1 billion per year, despite some concerns that it could cause liver damage. Earlier this year, the FDA imposed a partial clinical hold on the drug preventing new patients from being enrolled into studies.

Merck acknowledged at an R&D update last year that it had a pressing need to bolster its pipeline, particularly through external ‘bolt-on’ partnership deals, and get drugs through development and onto the market more quickly. It set a target of launching a new product every 18 months.

Shares in Merck fell 13% in the wake of the announcement.

Image by Dmitriy Gutarev from Pixabay