DX39
Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Stephen L Hauser, MD , University of California, San Francisco, San Francisco, CA
Ludwig Kappos, MD , University Hospital Basel, University of Basel, Basel, Switzerland
Xavier Montalban, MD, PhD , Vall d’Hebron University Hospital, Barcelona, Spain
Harold Koendgen, MD PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Carrie Li, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Carole Marcillat, Pharm. D , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Ashish Pradhan, MD , Genentech, Inc., South San Francisco, CA
David Wormser, MSc, MPhil PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX
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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 (OCR) 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.

Objectives:

To report ongoing safety evaluations from OCR clinical trials and open-label extensions (OLEs) up to September 2017.

Methods:

OCR 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 2,000 mg infusions through Week 24 (both doses split); treatment through Week 96 was OCR 600 mg (patients starting on 600 mg dose and those receiving placebo or interferon beta-1a (IFN β-1a) 30 μg) or 1,000 mg (those starting on OCR 2,000 mg). Comparators were placebo (ORATORIO and Phase II) and IFN β-1a (44 μg subcutaneous/three times weekly [OPERA] or 30 μg intramuscular/weekly [Phase II]). Patients completing controlled treatment periods could enroll in the OLE with OCR 600 mg/24 weeks. Data presented are from OCR 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 OCR, 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.