High-dose ocrelizumab has no additional benefit in PPMS

The phase 3b GAVOTTE trial confirmed the favourable benefit-risk profile of the approved 600-mg dose of ocrelizumab for patients with primary-progressive MS (PPMS). The results showed that increasing the dose to 1,200/1,800 mg did not improve control of disability progression.

Ocrelizumab is approved at 600 mg every 6 months for relapsing MS and PPMS. A post-hoc analysis of the phase 3 ORATORIO study (NCT01194570) suggested that higher serum concentrations were associated with reduced confirmed disability progression (CDP) without affecting safety. Based on this observation, the phase 3b, multicentre, randomised, double-blind, parallel-group GAVOTTE study (NCT04548999) was initiated to compare the efficacy and safety of a higher ocrelizumab dose (1,200/1,800 mg) with the approved 600 mg dose in PPMS.

Prof. Stephen Hauser (University of California, CA, USA) presented the results [1]. A total of 753 participants were randomised 2:1 to receive high-dose ocrelizumab (1,200 mg for participants <75 kg or 1,800 mg for participants ≥75 kg) or 600 mg every 24 weeks for ≥120 weeks. The primary endpoint was the time to onset of composite confirmed disease progression (cCDP), defined as a 12-week confirmed increase from baseline in any of the following: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FW) with a ≥20% increase, or 9-Hole Peg Test (9PHT) with a ≥20% increase.

At baseline, the mean age was 43 years, 53.1% of the participants were female, the mean weight was 72 kg, and the mean EDSS score was 4.5. High-dose ocrelizumab did not reduce the risk of disability progression compared with 600 mg (HR 0.95; 95% CI 0.76-1.18; P=0.64). In the high-dose and the 600-mg group, the EDSS score was 26.0 and 29.6, respectively (HR 0.86; 95% CI 0.65-1.15; P=0.32); the T25FW score was 38.7 and 41.8, respectively (HR 0.93; 95% CI 0.73-1.18; P=0.55); and the 9PHT score was 13.8 and 14.3, respectively (HR 0.96;95% CI 0.64-1.44; P=0.85). None of the secondary endpoints, including disability, cognition, brain volume, and neurofilament light (NfL), showed a significant benefit of higher-dose ocrelizumab. The increased dose, however, led to a greater depletion of CD19+ B cells. Safety outcomes were comparable across groups, with no new signals observed.

1. Hauser S, et al. Efficacy and safety of a body-weight–adjusted high dose of ocrelizumab vs standard dose in PPMS: primary results of the Phase IIIb GAVOTTE study. O129, ECTRIMS 2025 Congress, 24-26 September 2025, Barcelona, Spain.

Medical writing support was provided by Michiel Tent.

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Posted on 30 September 202530 September 2025