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5th Joint triennial congress of the European and Americas Committees
for Treatment and Research in Multiple Sclerosis
Amsterdam, The Netherlands
19.10.2011 - 22.10.2011 |
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Immunomodulation 1Thursday, October 20, 2011, 15:30 - 17:00Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis: week 96 results of a phase II, randomised, multicentre trialL. Kappos, D. Li, P. Calabresi, P. O'Connor, A. Bar-Or, F. Barkhof, M. Yin, D. Leppert, R. Glanzmann, J. Tinbergen, S.L. Hauser (Basel, CH; Vancouver, CA; Baltimore, US; Toronto, Montreal, CA; Amsterdam, NL; San Francisco, US)
Background: Ocrelizumab (OCR) is a humanised mAb targeting CD20 on B cells. In a phase II trial in RRMS, OCR led to a reduction of Gd+ lesions (primary endpoint) by >=89%, and of annualized relapse rate (ARR) by >=73% at wk 24, compared with placebo. Here we report the wk 96 data.
Methods: At baseline, 220 RRMS patients (pts) had been randomised 1:1:1:1 to receive iv OCR (days 1, 15) for a total dose of 600 mg (A), 2000 mg (B), placebo (C), or open-label weekly IFNbeta-1a 30 ug im (D). At wk 24, 48 and 72 all pts were treated with OCR: groups A, C and D received 600 mg per cycle; group B received 1000 mg at wk 24 and 48, and switched to 600 mg at wk 72. Results: 183 pts completed the wk 96 treatment period.
Efficacy: ARR was 0.18 [95% CI: 0.11-0.31] and 0.22 [0.13-0.35] for groups A and B for wks 0-96. In groups A and B, 67.3% and 76.4% had no relapses and no confirmed EDSS progression from wk 0-96 (“clinical disease activity free”); 78.2% and 80.0% of pts had been relapse-free. Only a small proportion of pts had 12 wk-confirmed EDSS progression at wk 96 (A: 12.7%; B: 7.3%; C: 13.0%; D: 9.3%). In an exploratory analysis, ARRs were reduced between wks 24-96 in pts switched from placebo to OCR (group D) from 0.64 to 0.20 [0.12-0.33], and in those switched from IFN to OCR (group C) from 0.36 to 0.16 [0.09-0.28]. At wk 96 there were no Gd-enhancing T1 lesions in all groups (A-D). In group B, one pt had 1 newly enlarging T2 lesion and another had 2 new T2 lesions. Total brain volume was reduced by 1.1/1.2% in Groups A/B, from wk 12-96. Safety: There was no imbalance in the total number of serious adverse events across all groups over 96 wks. Serious infection rates were similar for groups A and B (1.97 [0.49-7.98] and 1.93 [0.48-7.71] events/100 pt-yr) and did not increase with OCR retreatment. Infusion-related reactions were more common after the 1st OCR infusion, but decreased to placebo levels in subsequent infusions.
Conclusions: OCR effects of reducing Gd-enhancing lesions and ARR were well maintained over 96 wks. Switching from IFN or placebo to OCR resulted in similar sustained benefits.
LK has received grant support through the University Hospital Basel from Acorda Therapeutics Inc., Actelion Pharmaceuticals Ltd, Advancell, Allozyne, Barofold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, Boehringer Ingelheim, CSL Behring, Geneuro, Genmab, GlaxoSmithKline, Glenmark, Merck Serono, MediciNova, Novartis, Sanofi-Aventis, Santhera Pharmaceuticals, Shire Plc, Roche, Teva, UCB, and Wyeth; also from the Swiss MS Society, the Swiss National Research Foundation, Europen Union, Gianni Rubato, Roche and Novartis Foundations. DL is the Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Angiotech, Bayer, Berlex-Schering, Bio-MS, Centocor, Daiichi Sankyo, Genentech, Hoffmann-LaRoche, Merck-Serono, Perceptives, Schering-Plough, Teva Neurosciences, Sanofi-Aventis, and Transition Therapeutics. He has also acted as a consultant to Genzyme and Novartis. PC has received personal compensation for consulting and serving on scientific advisory boards from; Biogen-IDEC, Teva, Abbott, Vaccinex, and Novartis; and has received research funding from companies Biogen-IDEC, Teva, EMD-Serono, Abbott, Vertex, Genentech, and Bayer. PO has received support in the form of consultation fees or study grant support from the following companies: Bayer, Biogen Idec, EMD Serono, Novartis, Sanofi Aventis, Actelion, Eli Lilly, Genentech, Roche, and Warburg Pincus. A B-O has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from: Bayer, Bayhill Therapeutics, Berlex, Biogen-IDEC, BioMS, Diogenix, Eli-Lilly, Genentech, GSK, Guthy-Jackson/GGF, Merck-Serono, Novartis, Ono Pharmacia, Roche, Sanofi Aventis, Teva Neuroscience, and Wyeth. FB has has recieved consultancy fees from Merck-Serono, Novartis, Roche, Synthon BV, Bayer Schering Pharma and Sanofi-Aventis. MY is a full-time employee of Genentech, Inc. DL is an employee of F. Hoffmann – La Roche Ltd a member of the Roche Group. DL is an employee of Genentech, Inc., a member of the Roche Group. RG is an employee of Genentech, Inc., a member of the Roche Group. JT is an employee of F. Hoffmann – La Roche Ltd a member of the Roche Group. SH has the following conflicts of interest: Pfizer, Wyeth, Roche, Receptos, BioMarin.
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