Ocrelizumab Efficacy in PPMS Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase III, Placebo-Controlled Trial
Objectives: To evaluate the efficacy of OCR in patients with PPMS with and without T1 gadolinium-enhancing (Gd+) lesions at baseline in a Phase III, randomized, double-blind, placebo-controlled study (ORATORIO).
Methods: A total of 732 patients were randomized (2:1) to receive OCR 600 mg via intravenous (IV) infusions as two 300-mg infusions 14 days apart or placebo (PBO) every 24 weeks for ≥120 weeks until a prespecified number of 12-week confirmed disability progression (CDP) events occurred. Key eligibility criteria included: age 18-55 years, PPMS diagnosis (2005 revised McDonald criteria), and Expanded Disability Status Scale (EDSS) score of 3.0-6.5. The primary endpoint was time to onset of 12-week CDP. Secondary endpoints included time to onset of 24-week CDP and change in total T2 lesion volume from baseline to 120 weeks. Subgroup analyses evaluated these outcomes in patients with and without T1 Gd+ lesions at baseline.
Results: Compared with PBO, OCR significantly reduced risk of 12-week CDP by 24% (hazard ratio [HR]=0.76; p=0.0321), 24-week CDP by 25% (HR=0.75; p=0.0365), and T2 lesion volume (−3.4% with OCR vs +7.4% with PBO [p<0.0001]). T1 Gd+ lesions were present at baseline in 27.5% of OCR-treated patients vs 24.7% of PBO-treated patients. In patients with and without T1 Gd+ lesions at baseline, respectively, OCR reduced the risk of 12-week CDP by 35% (HR=0.65 [95% CI: 0.40–1.06]; p=0.0826) and 16% (HR=0.84 [95% CI: 0.62–1.13]; p=0.2441); the risk of 24-week CDP by 33% (HR=0.67 [95% CI: 0.40–1.14]; p=0.1417) and 19% (HR=0.81 [95% CI: 0.59–1.10]; p=0.1783); and total T2 lesion volume by −3.8% (95% CI: −7.0 to −0.5) with OCR vs 12.0% (95% CI: 7.2–17.1) with PBO (p<0.001) and −3.1% (95% CI: −5.0 to −1.1) with OCR vs 6.1 % (95% CI: 3.3–9.0) with PBO (p<0.001).
Conclusions: In ORATORIO, OCR reduced clinical and MRI disease activity vs PBO, including in patient subgroups with and without T1 Gd+lesions at baseline.
Supported by F. Hoffmann-La Roche Ltd.