Ravulizumab Superior in Preventing On-Trial Relapse in Subgroups of NMOSD

Michael Levy, MD, PhD

In a prespecified analysis of the CHAMPION-NMOSD (NCT04201262) open-label, phase 3 study, findings displayed ravulizumab (Ultomiris; Alexion) was superior in antiaquaporin (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) compared with placebo in prespecified subgroups by age, sex, race and geographic region.¹

The treatment was superior in preventing on-trial relapse in monotherapy (HR, 0.021; 95% CI, 0–0.176; relapse risk reduction [RRR], 97.9%; P <.0001) and immunosuppressive therapy (IST) groups (HR, 0.031; 95% CI, 0–0.234; RRR, 96.9%; P <.0001) compared with placebo based on time to first adjudicated on-trial relapse. Notably compared with placebo, significant differences were observed in patients who had previously received rituximab (n = 20; RRR, 93.7%; P = .0078) or not (n = 38; RRR, 98.1%; P <.0001).

These findings were presented as an abstract presentation at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by Michael Levy, MD, PhD, an associate professor at Harvard Medical School. The analysis evaluated the efficacy of the regimen in clinically relevant patients including ravulizumab monotherapy, concomitant IST use, age, sex, geographic region, and prior rituximab use.

In the CHAMPION-NMOSD trial, researchers evaluated the efficacy and safety of ravulizumab in 58 adult patients with anti-AQP4 NMOSD who had at least 1 attack or relapse in the 12 months prior to the screening visit. The participants also had Expanded Disability Status Scale scores of 7 or less, had a body weight of at least 40 kg at trial entry, and they were allowed to stay on stable supportive immunosuppressive therapy for the duration of the trial.

Adult patients received a weight-based intravenous loading dose of ravulizumab (2400–3000 mg), then a maintenance dose on day 15 (3000–3600 mg) and every 8 weeks following. The PREVENT trial (NCT01892345) placebo arm and eculizumab (Soliris; Alexion) availability precluded concurrent placebo control were used as an external comparator.

In the prespecified efficacy subgroup analyses of the trial, the primary end point was time to first adjudicated on-trial relapse. Additionally, across all of the subgroups, safety outcomes were analyzed. At baseline, 30 of 58 patients treated with ravulizumab received monotherapy, and 28 out of 58 recieved concomitant IST of either steroid (n = 12), azathioprine (n = 7), mycophenolate mofetil (n = 6) or other (n = 3). Notably, no patients treated with ravulizumab experienced a positively adjudicated on-trial relapse. As for the safety profile, it was consistent with that of patients on the treatment across other approved indications.

In the trial, treatment-emergent adverse events (AEs) were reported in 93.1% of patients on ravulizumab and serious AEs in 13.8% of patients. Two vaccinated patients had a meningococcal infection (2.4 out of 100 patient-years). Those affected patients recovered with no sequelae and 1 continued with the trial, no deaths were reported. The efficacy and safety data continued consistently with the primary treatment period despite the longer follow-up (median treatment duration, 90.9 weeks).

Originally FDA-approved in 2018, ravulizumab is indicated to treat adults with paroxysmal nocturnal hemoglobinuria. Later, in 2021, that indication was expanded to include children and adolescents. The regimen binds the same complement component 5 epitope as eculizumab and its longer half-life enables an extended dosing interval, at 8 weeks versus 2 weeks.

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REFERENCES
1. Levy M, Pittock S, Michael Barnett et al. Efficacy subgroup analyses from the phase 3 CHAMPION-NMOSD trial in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts. Abstract 003.