ACTRIMS 2023: Evobrutinib safely keeps relapse rates low after 4 years
Data comes from Phase 2 trial testing therapy against placebo, Tecfidera
Evobrutinib, an experimental BTK inhibitor being developed for people with relapsing forms of multiple sclerosis (MS), continues to be well tolerated and is showing low relapse rates after four years of treatment.
That’s according to new data spanning a Phase 2 trial (NCT02975349) that tested evobrutinib against a placebo and the approved MS treatment Tecfidera (dimethyl fumarate), and its open-label extension study where all the participants are receiving evobrutinib.
The new findings will be presented today at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, Feb. 23-25 virtually and in San Diego, California.
The poster, titled, “Efficacy and Safety of the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib for Relapsing Multiple Sclerosis Over 3.5 Years of Treatment: An Ongoing Phase II Open-Label Extension,” was led by researchers at Merck KGaA (known as EMD Serono in North America) the company developing evobrutinib.
“This new long-term data complements previously presented data demonstrating evobrutinib’s impact on novel markers indicative of progression independent of relapse, such as slowly expanding lesions. Together, these data highlight evobrutinib’s potential to deliver a safe and highly efficacious option for people living with [relapsing MS],” said Jan Klatt, senior vice president and head of development unit neurology and immunology at Merck, in a company press release.
Evobrutinib is an investigational oral treatment designed to block the Bruton’s tyrosine kinase (BTK) protein, which is essential for B-cells — immune cells implicated in the development of MS — to survive and function. It’s expected to dampen inflammation and slow disease progression by reducing B-cell numbers and lowering other immune cell types’ activation.
The Phase 2 clinical trial enrolled 267 patients with either relapsing-remitting MS (RRMS) or active secondary progressive MS (SPMS).
Effectiveness, safety of evobrutinib
The participants were randomly assigned to one of five groups. Three groups received evobrutinib at different doses — 25 mg once daily, 75 mg once daily, or 75 mg twice daily. The other two groups were given a placebo or Tecfidera and were used as controls.
Participants in the evobrutinib and Tecfidera groups received their assigned treatment for 48 weeks (nearly one year), while those in the placebo arm received it for 24 weeks and were then switched to 25 mg of evobrutinib.
Results from the trial showed the 75 mg twice daily dose of evobrutinib significantly reduced MS disease activity after 24 weeks, with patients having significant decreases in the number of lesions with active inflammation and relapse rates compared with those on a placebo.
After a year of treatment, patients with the higher dose had a mean of 0.11 relapses per year, while those on a placebo had 0.37 relapses a year in the first 24 weeks before switching to evobrutinib.
After completing the placebo-controlled part, participants were invited to join the trial’s open label extension, wherein all received 75 mg evobrutinib once daily for a year, on average, before switching to the 75 mg twice daily dose.
Data shared at the ACTRIMS Forum, spanning 228 weeks in the trial and extension part, showed relapse rates continued to fall after four years of treatment.
Regardless of their assigned treatment in the randomized part, patients saw a mean of 0.13 relapses a year throughout the four years. The initial rate in the extension part was 0.19 relapses a year with 75 mg evobrutinib once daily, but it lowered even further to 0.1 relapses a year after the switch to 75 mg twice daily.
Relapse rates remained low for those who received the highest dose from the start — 0.12 relapses a year at week 228.
Evobrutinib continued to be well tolerated throughout the four years. Most side effects were mild to moderate, with seven patients (3.3%) having a serious treatment-emergent side effect. There was no increase in side effects after patients switched to the highest dose in the extension part.
Two ongoing Phase 3 trials — EVOLUTION RMS1 (NCT04338022) and EVOLUTION RMS2 (NCT04338061) — are comparing the safety and effectiveness of evobrutinib against Aubagio (teriflunomide), an approved MS treatment, in more than 1,800 participants.
“We look forward to presenting detailed results from our fully enrolled Phase III clinical trials in the near future,” Klatt said.
Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2023 Feb. 23-25. Go here to see the latest stories from the conference. Follow along on Facebook, Twitter, and Instagram for live updates using the hashtag #actrims2023.