Two-year results of the Phase IIIb CHORDS study evaluating ocrelizumab effectiveness and safety in patients with relapsing-remitting multiple sclerosis who had a suboptimal response with prior disease-modifying therapy (2906)

Objective: To report the 2-year Phase IIIb CHORDS study (NCT02637856) results evaluating ocrelizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and suboptimal response to previous disease-modifying therapy (DMT). Background: Ocrelizumab was superior to interferon β-1a in patients with relapsing MS (OPERA I and II). Evaluating ocrelizumab effectiveness in patients with suboptimal response to DMT is needed. Design/Methods: The CHORDS intention-to-treat (ITT) population (N=608) had suboptimal response (≥1 relapse, ≥1 T1 gadolinium-enhancing lesion(s) or ≥2 new/enlarging T2 lesions) to previous DMT after stable use (≥6 months). Patients received ocrelizumab 600 mg every 24 weeks for ≤96 weeks. The primary endpoint was the proportion of patients free of protocol-defined clinical or MRI activity (event), evaluated in a modified ITT population which imputed patients who terminated early for lack of efficacy or death as had an event and excluded patients who discontinued for other reasons without an event. Key secondary endpoints included annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change from baseline. Safety was assessed in the ITT population. Results: A total of 555 patients completed treatment (baseline mean [SD] duration since first MS symptom and diagnosis, 5.4 [3.24] and 4.2 [3.03] years, respectively). At Week 96, 48.1% of patients were free of protocol-defined events. Most did not experience protocol-defined relapse (89.6%), any T1 gadolinium-enhancing lesions (95.5%) or new/enlarging T2 lesions (59.5%) or 24-week confirmed disability progression (89.6%). The ITT adjusted ARR was 0.046. Seventy-one relapses were observed (Year 1, 50; Year 2, 21). At Week 96, most patients had stable ( Conclusions: This analysis demonstrates ocrelizumab treatment responses over 2 years in patients with RRMS who are relatively early in the disease course and experienced suboptimal response to another DMT. Disclosure: Dr. Weinstock-Guttman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, , Novartis, Genentech, EMD Serono, Abbvie, Mallickrodt, Bristol Myers.. Dr. Weinstock-Guttman has received research support from Biogen, Novartis, Genentech, and EMD Serono..Dr. Bermel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Genentech, Novartis. Dr. Bermel has received royalty, license fees, or contractual rights payments from intellectual property underlying the Multiple Sclerosis Performance Test, currently licensed to Qr8 Health and Biogen. Dr. Bermel has received research support from Biogen, Genentech, and Novartis. Dr. Csoboth has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Cutter has received personal compensation from AMO Pharma, Argenix, Atara Bio-therapeutics, Axon, Biogen, BioLineRx, Bio-therapeutics, Brainstorm Cell Therapeutics, Charleston Laboratories, Inc., Click Therapeutics, Genentech, Genzyme, GW Pharma, Horizon Pharmaceuticals, Klein Buendel Inc., MedDay, MedImmune, Merck, Merck/Pfizer, Neurim, Novartis OPKO Biologics, Orphazyme, Pythagoras, Inc, Reata Pharmaceuticals, Receptos/ Celgene, Sanofi- Aventis, Roche, SciFluor, Somahlution, Teva Pharma-ceuticals, TG Therapeutics, UTHealth Houston Teva NeuroscienceDr. Freedman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Serono Canada, Genzyme, Merck Serono, Novartis, F. Hoffmann-La Roche Ltd, Sanofi-Aventis and Teva Canada Innovation. Dr. Freedman has received compensation for serving on the Board of Directors of Actelion, Bayer Healthcare, Biogen Idec, Clene Nanomedicine, F. Hoffmann-La Roche Ltd, Merck Serono, MedDay Pharmaceuticals, Novartis and Sanofi-Aventis. Dr. Freedman has received research support from Genzyme Canada. Dr. Leist has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience. Dr. Leist has received research support from received consultancy fees or clinical research grants from Acorda, Bayer, Biogen, Daiichi, EMD Serono, Novartis, ONO, Pfizer, Teva Neuroscience. Dr. Ma has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Musch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Reder has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, F. Hoffmann-La Roche Ltd, Genentech, Inc., Merck Serono, Novartis and TG Therapeutics. Dr. Reder has received personal compensation in an editorial capacity for MedLink. Dr. Reder has received research support from Bayer, Biogen, F. Hoffmann-La Roche Ltd, Genentech, Inc., Mallinckrodt, Merck Serono and Novartis. Dr. Stankiewicz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Genzyme, Genentech, Inc., EMD Serono, Novartis, and Celgene.Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for consulting, scientific advisory boards, or other activities with Alkermes, Actelion, Acorda Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanof. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from Royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.