Abstract: Prespecified Subgroup Analyses of Ocrelizumab Efficacy in Patients with Primary Progressive Multiple Sclerosis from the Phase III Oratorio Study (2018 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

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Prespecified Subgroup Analyses of Ocrelizumab Efficacy in Patients with Primary Progressive Multiple Sclerosis from the Phase III Oratorio Study

Thursday, May 31, 2018

Exhibit Hall A (Nashville Music City Center)

Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX

Xavier Montalban, MD, PhD , Division of Neurology, University of Toronto, Toronto, ON, Canada

Stephen L Hauser, MD , University of California, San Francisco, San Francisco, CA

Ludwig Kappos, MD , University Hospital Basel, University of Basel, Basel, Switzerland

Laura Julian, PhD , Genentech, Inc., South San Francisco, CA

Marianna Manfrini, MD PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland

Shibeshih Belachew, MD, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland

Fabian Model, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland

Stanislas Hubeaux, MSc , F. Hoffmann-La Roche Ltd, Basel, Switzerland

Amit Bar-Or, MD , University of Pennsylvania, Philadelphia, PA

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Background:

Ocrelizumab (OCR), a humanized, CD20⁺ B cell-selective monoclonal antibody, showed superior efficacy vs placebo (PBO) in patients with primary progressive multiple sclerosis (PPMS) in the Phase III ORATORIO study (NCT01194570). The primary endpoint was 12-week confirmed disability progression (CDP).

Objectives:

To evaluate the effects of OCR vs PBO on clinical and imaging outcomes in prespecified subgroups of patients with PPMS from the ORATORIO study.

Methods:

Patients were randomized (2:1) to OCR 600 mg or PBO every 24 weeks for ≥120 weeks and until a prespecified number of CDP events occurred. The treatment effect of OCR on 12-week CDP was analyzed in prespecified, baseline characteristic-based subgroups (age, sex, region, body mass index, body weight, Expanded Disability Status Scale score, T1 gadolinium-enhancing [T1 Gd⁺] lesions, prior MS disease-modifying treatment, and duration of MS since symptom onset). Additional analyses of clinical and imaging outcomes were performed for subgroup comparisons that showed a trend for differences in treatment effect (nominal interaction p<0.3 on the primary endpoint). Univariate and multivariate analyses were based on Cox regression, negative-binomial regression or mixed models of repeated measures, depending on outcome. The study was not powered to demonstrate efficacy within subgroups or differences between subgroups.

Results:

No differences in the magnitude of OCR treatment effect on the primary endpoint between all prespecified subgroups were statistically significant in univariate or multivariate Cox regression analyses (all interactions p>0.05; OCR n=487; PBO n=244). Numerical differences in treatment effect were observed within subgroups based on sex, T1 Gd⁺ lesions and age (interaction p<0.3). On 12-week CDP, males seemed to derive more benefit; however, male and female patients benefited from OCR on key clinical and imaging secondary and exploratory endpoints. Although the effect of OCR was generally larger in patients with baseline T1 Gd⁺ lesions and/or at a younger age, older patients and those with no baseline T1 Gd⁺ lesions also derived benefit across key endpoints. The differences observed between age subgroups might be partially due to the higher prevalence of MRI features of acute inflammatory activity in younger patients.

Conclusions:

Directionally consistent point estimates favoring ocrelizumab vs PBO were seen across all clinical and MRI endpoints in prespecified subgroups of the ORATORIO study.

DX42 Prespecified Subgroup Analyses of Ocrelizumab Efficacy in Patients with Primary Progressive Multiple Sclerosis from the Phase III Oratorio Study

DX42
Prespecified Subgroup Analyses of Ocrelizumab Efficacy in Patients with Primary Progressive Multiple Sclerosis from the Phase III Oratorio Study