High-dose ocrelizumab has no additional benefit in PPMS

The phase 3b GAVOTTE trial confirmed the favourable risk–benefit profile of the approved 600 mg dose of ocrelizumab for patients with primary-progressive multiple sclerosis (PPMS). The results showed that increasing the dose to 1,200 or 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 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 or 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 disability 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 (9HPT) 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 for both arms. High-dose ocrelizumab did not reduce the risk of disability progression compared with 600 mg (see Figure). The EDSS, T25FW, and 9HPT scores in the high-dose and the 600 mg dose groups are also shown.

Figure: No reduced risk of disability progression with high-dose ocrelizumab in PPMS [1]



9HPT, 9-Hole Peg Test; cCDP, composite confirmed disability progression; EDSS, Expanded Disability Status Scale; PPMS, primary-progressive multiple sclerosis; T25FW, Timed 25-Foot Walk Test.

None of the secondary endpoints, including disability measured as 24-week CDP or 23-week confirmed Progression Independent Relapse Activity (cPIRA), cognition (Multiple Sclerosis Walking Scale [MSWS] or  Symbol Digit Modalities Test [SDMT] worsening), brain volume or thalamic volume loss, and neurofilament light chain, showed a significant benefit of higher-dose ocrelizumab. The increased dose, however, led to a greater depletion of CD19+ B cells. Using a very low threshold for depletion of ≤0.4 cells, the difference was 10.8% (30.8 vs 20.0%). 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.

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Posted on 25 November 202525 November 2025