Abstract: Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis over 2.5 Years of the Open-Label Extension to a Phase II Trial (2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

DMT02
Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis over 2.5 Years of the Open-Label Extension to a Phase II Trial

Thursday, June 2, 2022: 2:50 PM

Woodrow Wilson D (Gaylord National Resort & Convention Center)

Xavier Montalban, MD PhD , Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d’Hebron, Barcelona, Spain

Jerry S Wolinsky, MD , McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX

Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, Montréal, QC, Canada, NeuroRx Research, Montréal, QC, Canada

Martin S Weber, MD , Institute of Neuropathology and Department of Neurology, University Medical Center, University of Göttingen, Göttingen, Germany

Ivan Staikov, MD PhD , Department of Neurology, Acibadem City Clinic Tokuda Hospital, Sofia, Bulgaria

Karolina Piasecka-Stryczynska, PhD , Department of Neurology and Cerebrovascular Diseases, Poznań University of Medical Sciences, Poznań, Poland

Davorka Tomic, PhD , Ares Trading SA, an affiliate of Merck KGaA, Darmstadt, Germany, Eysins, Switzerland

Emily C Martin, PhD , EMD Serono, Billerica, MA

Kristina H Holmberg, PhD , EMD Serono, Billerica, MA

Hans Guehring, MD , The healthcare business of Merck KGaA, Darmstadt, Germany

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Background: Evobrutinib—a covalent, central nervous system (CNS)-penetrating Bruton’s kinase inhibitor—was well tolerated and effective at reducing gadolinium-enhancing lesions in a double-blind, randomized Phase II trial in patients with relapsing multiple sclerosis (pwRMS; NCT02975349).

Objectives: Report the safety and efficacy of evobrutinib over 2.5 years in an open-label extension (OLE).

Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25 mg once-daily at W24), evobrutinib 25 mg, 75 mg once-daily, 75 mg twice-daily, or open-label dimethyl fumarate (DMF; 240 mg twice-daily). At W48, patients could enter the OLE (DMF: 4–8W washout); evobrutinib 75 mg once-daily (median ~48W), then 75 mg twice-daily. The latest available OLE data are reported here.

Results: Of 267 DBP patients, 213 (80%) entered the OLE; 164 (61%) completed ≥132W of OLE treatment. Treatment-emergent adverse events (TEAEs) were reported by 165/213 patients (77.5%); 59 (27.7%) had a treatment-related TEAE. Six serious TEAEs were deemed treatment-related. Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%); 3 were fatal (COVID-19 pneumonia [n=2] and E. coli sepsis [n=1]; not considered treatment-related). At OLE W120, most patients had IgG (91%), IgA (88%), and IgM (82%) levels within normal ranges. Overall mean CD19+ B-cell levels were 0.218x10⁶ cells/mL (OLE baseline) and 0.122x10⁶ cells/mL (OLE W96). ALT/AST elevations were observed only in patients previously receiving DMF/evobrutinib 25 mg and occurred within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, but without clinical signs and symptoms. Based on all available OLE data, ARR was 0.12 (95% CI 0.07–0.20) for patients receiving 75mg twice-daily in the DBP.

Conclusions: Evobrutinib safety and efficacy data over 2.5 years in pwRMS continue to show acceptable tolerability and maintained efficacy, with no new safety signals.

Role of the Study Sponsor: This study was sponsored by EMD Serono Research and Development Institute, Inc. The study sponsor was involved in the study design, collection, analysis, and interpretation of data, and was involved in the decision to submit the abstract for publication.

DMT02 Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis over 2.5 Years of the Open-Label Extension to a Phase II Trial

DMT02
Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis over 2.5 Years of the Open-Label Extension to a Phase II Trial