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Ravulizumab significantly reduced relapses in AQP4+ NMOSD

Presented by
Dr Sean Pittock, Mayo Clinic, MN, USA
In a placebo-controlled study, ravulizumab, a monoclonal antibody against  complement C5, was highly effective in reducing the risk of relapse in patients with anti-aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD). No relapses were observed over a median follow-up of 73.5 weeks in the open-label, phase 3, externally-controlled CHAMPION-NMOSD trial. Ravulizumab, given every 8 weeks because of long-half life, was well tolerated.

A placebo-controlled trial studying ravulizumab in NMOSD was deemed unethical because of the availability of eculizumab and other medications, explained Dr Sean Pittock (Mayo Clinic, MN, USA) [1]. A non-inferiority trial was unfeasible due to the rarity of AQP4+ NMOSD. Instead, the CHAMPION-NMOSD trial (NCT04201262) used the placebo group from the PREVENT trial (NCT01892345) investigating eculizumab. Propensity scores were used to account for potential confounders introduced by this comparator. Ravulizumab binds the same complement component 5-epitope as eculizumab, but has a longer elimination half-life, allowing for an extended dosing interval of 8 rather than 2 weeks.

Participants aged 18 years or older received a weight-based, IV loading dose of ravulizumab (2,400–3,000 mg) on day 1, followed by weight-based maintenance doses (3,000–3,600 mg) on day 15 and once every 8 weeks thereafter. The 58 participants on ravulizumab and 47 on placebo had a mean follow-up of 73.5 and 36.0 weeks, respectively.

The study met its primary endpoint, which was the time to first adjudicated, on-trial relapse and relapse-risk reduction (RRR). There were 0 on-trial relapses in the ravulizumab group versus 20 in the placebo group (P<0.0001), representing an RRR of 98.6%. The percentage of relapse-free participants at 48 weeks was 100% with ravulizumab and 63% with placebo. A key secondary efficacy endpoint, the adjudicated on-trial annualised relapse rate (ARR), was 0.00 with ravulizumab. This was superior to a predefined comparator ARR of 0.25 as well as the ARR of 0.42 in the placebo group (see Table for all secondary outcomes).

Table: Secondary endpoint results of the CHAMPION-NMOSD trial [1]

aBecause statistical significance for clinically important change from baseline in EQ-5D score was not met, P-values for the subsequent lower-ranking secondary endpoints are not significant; therefore, nominal P-values are presented.

ARR, annualised relapse rate; CI, confidence interval; EDSS, Expanded Disability Status Scale; HAI, Hauser Ambulation Index; N/A, not applicable; SD, standard deviation; VAS, visual analogue scale.

Ravulizumab was well tolerated, with a safety profile consistent with that of eculizumab. No unexpected patterns were observed in the treatment-emergent adverse events, which were reported in 93.1% versus 95.7% of participants in the experimental and placebo group, respectively. Serious adverse events were seen in 13.8% versus 55.3% of the participants. There were 2 cases of meningococcal infection in the ravulizumab group, which recovered with no sequelae. Their occurrence does highlight the need for close monitoring and risk evaluation.

  1. Pittock SJ. Efficacy and safety of ravulizumab in adults with anti-aquaporin-4 antibody positive neuromyelitis optica spectrum disorder: outcomes from the phase 3 CHAMPION-NMOSD trial. Abstract O051, ECRIMS 2022, 26–28 October, Amsterdam, the Netherlands.

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