Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary progressive Multiple Sclerosis

Objective: To report ongoing safety evaluations from ocrelizumab clinical trials and open-label extensions (OLEs) up to September 2017. Background: Ongoing safety reporting on disease-modifying therapies for multiple sclerosis (MS) is crucial to understanding the long-term benefit–risk profile. Data are reported from patients receiving ocrelizumab in one Phase II study in relapsing-remitting MS (RRMS; NCT00676715), two identical Phase III trials in relapsing MS (RMS; OPERA I/II [NCT01247324]/[NCT01412333]) and the Phase III trial in primary progressive MS (PPMS; ORATORIO [NCT01194570]) and their extensions. Design/Methods: Ocrelizumab recipients received 600 mg doses intravenously every 24 weeks in OPERA I/II (96 weeks; first dose: 2×300 mg infusions split by 14 days) and ORATORIO (≥120 weeks; all doses split). Patients in the Phase II study received 600 mg or 2000 mg infusions through Week 24 (both doses split); treatment through Week 96 was ocrelizumab 600 mg (patients starting on 600 mg dose and those receiving placebo or interferon beta-1a 30μg) or 1000 mg (those starting on ocrelizumab 2000 mg). Comparators were placebo (ORATORIO and Phase II) and interferon beta-1a (44μg subcutaneous/three times weekly [OPERA] or 30μg intramuscular/weekly [Phase II]). Patients completing controlled-treatment periods could enroll in the OLE with ocrelizumab 600 mg/24 weeks. Data presented are from ocrelizumab recipients including those switching from comparators. Long-term safety data will continue to be reported on a regular basis. Results: As of February 2017, 2,301 patients with MS received ocrelizumab, resulting in 7,748 patient-years of exposure. Reported rates per 100 patient-years (95% confidence interval) were as follows: adverse events (AEs), 226 (222–229); serious AEs, 7.18 (6.59–7.80); infections, 71.3 (69.5–73.2); serious infections, 1.86 (1.57–2.19); and malignancy 0.454 (0.316–0.632). Updated cross-trial information using a September 2017 data-cut will be presented. Conclusions: The updated safety profile in the ocrelizumab MS all-exposure population is generally consistent with that seen during the controlled-treatment period in the RMS and PPMS populations. Study Supported by: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK. Disclosure: Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon, Bionure, Molecular Stethoscope. Dr. Hauser has received compensation for serving on the Board of Directors of Neurona. Dr. Kappos has received research support from Bayer HealthCare Pharmaceuticals, Biogen, F. Hoffmann-La Roche Ltd and Genentech,Novartis, Research grants from: the European Union, Roche Research Foundation, Swiss Multiple Sclerosis Society and Swiss National Research Foundation. Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi and Teva Pharmaceutical. Dr. Koendgen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I am an Employee of F.Hoffann-La Roche. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I am an Employee of F.Hoffmann-La Roche. Dr. Marcillat has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I am an Employee of F.Hoffmann-La Roche. Dr. Pradhan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I am an Employee of Genentech Inc. Dr. Wormser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has served on advisory boards and data monitoring or steering committees, has held consulting agreements or has received speaker honoraria from AbbVie, Alkermes, Biogen, Bionest, Clene Nanomedicine, EMD Serono, Forward Pharma, MedDay, Pharmaceuticals, Nov. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from royalties for monoclonal antibodies out-licensed to Chemicon International through UTHealth.