The EVOLUTION phase 3 clinical trials showed evobrutinib did not meet its primary endpoint of annualized relapse rate for up to 156 weeks compared to oral teriflunomide. Why?
Merck’s press release on the Evobrutinib vs Teriflunomide phase 3 EVOLUTION trials says more about teriflunomide than evobrutinib, but they do raise questions about all the other Bruton Tyrosine Kinase Inhibitors (BTKi) in clinical trials in MS and other autoimmune diseases.
05 DEC 2023 | DARMSTADT, GERMANY
“Results from the EVOLUTION clinical trials showed evobrutinib did not meet its primary endpoint of annualized relapse rate for up to 156 weeks compared to oral teriflunomide in both studies.
Merck, a leading science and technology company, today announced that its two Phase III EVOLUTION clinical trials (evolutionRMS 1 and evolutionRMS 2) investigating the efficacy and safety of evobrutinib did not meet their primary endpoints of reducing annualized relapse rates (ARR) in people with relapsing multiple sclerosis (RMS) compared to oral teriflunomide (0.11 vs. 0.11 in evolutionRMS 1 and 0.15 for evobrutinib vs. 0.14 for teriflunomide in evolutionRMS 2, p=NS in both trials). Of note, teriflunomide ARR values were lower than reported in other recent Phase III studies. The overall safety and tolerability profile was consistent with results from the previously reported Phase II trial. The company will complete a full evaluation of the data from the EVOLUTION clinical trials and will work with investigators on the future presentation and publication of the results.”
Teriflunomide clearly performed much better than expected and surprised Merck. Why?
I changed my mind about teriflunomide several years ago. I now think teriflunomide is the most underrated DMT in our therapeutic armamentarium. I also predict it will eventually become one of the most used MS DMTs once its alternative mode of action becomes widely known, we understand its efficacy profile, and we change how we use it in MS. There are several reasons for this.
Teriflunomide is much more effective as a DMT than we realize
As we reinterpret old data and new data emerge, it is clear that when we go beyond focal inflammation (relapses and MRI activity), teriflunomide is much more effective than we would expect based on its impact on relapses and MRI activity. Despite reducing relapses by, on average, a third, teriflunomide has a remarkably robust effect on disability progression and slows the accelerated brain volume loss due to MS.
The head-2-head studies of ofatumumab and ublituximab (anti-CD20 therapies) against teriflunomide show that despite both anti-CD20 agents being superior to teriflunomide in suppressing relapses and focal MRI activity, only ofatumumab was more effective than teriflunomide when it came to reduced disability worsening. The latter difference, however, was very small and not clinically significant. The difference was mainly driven by relapse-associated worsening (RAW), as the absolute differences between ofatumumab and teriflunomide on PIRA (progression independent on relapse activity) are small (EAN 2020). Please note that ublituximab was no better than teriflunomide on disability progression (see figures below). When assessing the more objective brain volume loss, an integrator of end-organ damage, teriflunomide, was equivalent to both these agents in slowing MS-related accelerated brain volume loss (BVL) (see figure by clicking here as well as much more to read).
======================================
Stay informed with MS information, news and resources. Sign-up Here: https://bit.ly/3NkMIeR
Visit the MS Views and News articles and videos archives: https://wwwmsviewsandrelatednews.blog
Visit us on Facebook: www.facebook.com/msviewsandnews
Visit us on Twitter (X): www.twitter.com/MSViewsandNews
Visit us on Instagram: www.instagram.com/msviewsandnews