The vice president of Global Program Leadership in Neurology and Immunology at EMD Serono discussed the recent long-term phase 2 data on evobrutinib presented at CMSC 2020.
Robert Henderson, PhD
Last week, phase 2 data presented at the 2020 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC 2020) showed that 75-mg evobrutinib maintained its efficacy and safety over the long-term in the treatment of patients with relapsing multiple sclerosis (MS).1
The phase 2 randomized controlled trial (NCT02975349) included 213 patients (79.8% of the 267 randomized) who were treated for 108 weeks, which consisted of the 48-week main study and 60-week open-label extension. Those who received EMD Serono’s investigational, oral, highly selective Bruton's tyrosine kinase (BTK) inhibitor had an annualized relapse rate (ARR) of 0.11 (95% CI, 0.04—0.25) at Week 48, and 0.12 (95% CI, 0.06–0.22) for the full 108-week period. Evobrutinib was also considered generally well-tolerated, maintaining its known safety profile during the open-label extension period, with transient elevated liver aminotransferases, which was reported in the 48-week double-blind period, not observed in the extension.2
To find out more about the data and what the clinical community can take away from the findings, NeurologyLive spoke with Robert Henderson, PhD, vice president, Global Program Leadership, Neurology and Immunology, EMD Serono.
Robert Henderson, PhD: There are several key takeaways for physicians related to the long-term safety and efficacy data on evobrutinib presented at both EAN and CMSC. Investigational evobrutinib is the first and only BTK inhibitor to demonstrate high and sustained efficacy through 108 weeks in clinical studies. ARR results in the double-blind phase of the study were maintained over the open-label extension (OLE), with patients receiving evobrutinib 75mg BID in the double-blind phase showing an ARR of 0.11 at Week 48, and of 0.12 for the 108-week period.
Additionally, no new safety signals were identified in the 60-week OLE, which is consistent with data seen in more than 1,200 patients who have received evobrutinib to date, across MS and other conditions. We are encouraged by this breadth of consistent safety data, including no increase of serious infections, as well as no LFT elevations during the OLE.
Finally, it provides even further information on the impact of BTK occupancy related to efficacy. Modeling data shows that greater than 95% BTK occupancy at trough is necessary in nearly all patients to achieve highest efficacy and this can be best achieved with BID dosing.
These data add to the growing, promising body of evidence related to efficacy and safety for investigational evobrutinib. There is a significant unmet need in multiple sclerosis treatment — there is a need for more efficacious oral therapies and especially with regards to impact on disease progression. In addition, there is further opportunity to advance on the benefit-risk of efficacious therapies with respect to systemic side effects and serious infections. The growing body of evidence suggests that evobrutinib has the potential to address these needs of MS patients by a novel mechanism of action, addressing both the adaptive and innate pathobiology of MS.
Evobrutinib is entering phase 3 trials following the results of the phase 2 clinical trial, which met its primary endpoint over 24 weeks of treatment. The two new trials, EVOLUTION RMS 1 and 2 are multi-center, randomized, parallel-group, double-blind, double-dummy, active-controlled studies of evobrutinib with teriflunomide, in participants with RMS. Each trial’s primary endpoint is patients’ ARR after 96 weeks of treatment. Secondary endpoints include the appearance of new or enlarging T2 lesions assessed by MRI scans and progressing disability as measured by the Expanded Disability Status Scale (EDSS). The phase 3 EVOLUTION studies will be starting shortly.
Transcript edited for clarity. For more coverage of CMSC 2020, click here.
1. Montalban C, Arnold DL, Weber MS, et al. Efficacy and Safety of the Bruton’s Tyrosine Kinase Inhibitor (BTKI) Evobrutinib in Relapsing Multiple Sclerosis over 108 Weeks: Open-Label Extension to a Phase 2 Study. Int J MS Care. 2020;22(2 Suppl). Late-Breaking Abstract.
2. New Late-Breaking Data at EAN Indicate Evobrutinib is the First BTK Inhibitor to Report Efficacy and Safety in MS Over 108 Weeks [press release]. Rockland, MA: EMD Serono; Published May 23, 2020. Accessed May 26, 2020. biospace.com/article/releases/new-late-breaking-data-at-ean-indicate-evobrutinib-is-the-first-btk-inhibitor-to-report-efficacy-and-safety-in-ms-over-108-weeks