Merck KGaA announced that its two phase 3 clinical trials investigating key pipeline candidate evobrutinib did not meet primary endpoints of reducing annualized relapse rates (ARR) in people with relapsing multiple sclerosis.
The EVOLUTION clinical trial program consists of two randomized, double-blind phase 3 studies — evolutionRMS 1 and evolutionRMS 2 — evaluating Merck's Bruton’s tyrosine kinase (BTK) inhibitor, oral evobrutinib, twice-daily versus oral teriflunomide (Sanofi's Aubagio), once-daily in people with relapsing MS.
A blockbuster hopeful, evobrutinib is designed to modulate B cell responses such as proliferation and antibody and cytokine release, with the idea that the BTK inhibitor can reach the central nervous system to target neuroinflammation at its source.
But according to Merck, in the evolutionRMS 1 trial, the ARRs were the same for both evobrutinib and teriflunomide and in the second trial, evolutionRMS 2, the ARRs were 0.15 for evobrutinib versus 0.14 for teriflunomide.
Merck was hoping the drug would best Sanofi's older oral pyrimidine synthesis inhibitor, Aubagio, first approved in 2012. Sanofi is also betting on BTK inhibitors in MS, with its own candidate, tolebrutinib. Sanofi jumped into the BTK space back in 2020, when it paid $3.7 billion to buy Principia Biopharma.
The drugmaker ran into a snag in June 2022, when the FDA placed phase 3 studies of tolebrutinib in multiple sclerosis and myasthenia gravis on partial clinical hold as a result of drug-induced liver injury that was identified with drug exposure — a similar issue faced by Merck when the EVOLUTION trials were put on hold back in April.
But despite the setback, Sanofi expects to submit tolebrutinib to regulators next year. Roche’s Genentech is also studying a BTK inhibitor, fenebrutinib in relapsing MS, with an anticipated submission date of 2026.
