Merck KGaA is back with another update on the durability of its BTK inhibitor evobrutinib, sharing data that show the effect on relapse rates lasts for at least five years. But with the program on partial clinical hold and phase 3 data imminent, the update may soon be overshadowed by other developments.
Germany-based Merck offered participants in its 48-week phase 2 trial the chance to join an open-label extension after it wrapped up the double-blind portion of the study. Since then, researchers have tracked the effect of 75-mg twice-daily evobrutinib dosing on patients with relapsing multiple sclerosis. Merck now has 240 weeks, almost five years, of data on more than 100 participants in the extension study.
The drugmaker used the ECTRIMS-ACTRIMS meeting in Milan to share (PDF) updated data. The overall pooled annualized relapse rate (ARR) was 0.11 in the latest analysis, compared to 0.08 at Week 24 at the twice-daily dose in the randomized study. ARR on placebo at Week 24 was 0.37.
Merck provided further evidence that evobrutinib delivers lasting benefits by analyzing the proportion of patients who were free from relapses and disability progression. The company found 87.1% of people had no clinical worsening in Year 5.
Safety is a key concern for evobrutinib and other BTK inhibitors. The FDA has imposed a series of partial clinical holds on candidates in the class over liver injury concerns, but the safety profile in the relatively small phase 2 extension looks fairly clean. Around 3% of subjects experienced serious treatment-related adverse events.
Merck and its rivals for the BTK inhibitor opportunity have typically encountered the liver injury risk as they have tested their molecules in larger patient populations. The FDA put a partial hold on evobrutinib in April, by when Merck had already completed enrollment in its phase 3 program. Merck is scheduled (PDF) to post phase 3 data by the end of the year. Sanofi recently delayed phase 3 readouts until 2024.