The agency requested modifications to the REMS program, seeking validation of patients’ meningococcal vaccination status and prophylactic administration of antibodies prior to giving ravulizumab treatment.
The FDA has issued a complete response letter (CRL) to AstraZeneca for the supplemental biologics license application (sBLA) of ravulizumab (Ultomiris) as a potential treatment for patients with neuromyelitis optica spectrum disorder (NMOSD). In its response, the agency did not raise concerns about the provided evidence for the therapy, rather it requested modifications to enhance the Risk Evaluation and Mitigation Strategy (REMS) program.1
According to an announcement from the company, the requested modifications are in reference to validate patients’ meningococcal vaccination status or prophylactic administration of antibodies prior to receiving treatment. AstraZeneca is expected to work with the FDA to determine the next steps for the REMS modifications and will not need any additional analysis or reanalysis of the phase 3 CHAMPION-NMOSD study (NCT04201262), the supporting trial for ravulizumab’s sBLA. Ravulizumab remains an approved treatment for patients with NMOSD in the European Union, Japan, and other countries.
In CHAMPION-NMOSD, ravulizumab, a long-acting C5 complement inhibitor, met its primary end point of time to first on-trial relapse, with no relapses observed in 58 patients with anti-aquaporin-4 NMOSD over a 73-week treatment period. Previously approved as a medication for myasthenia gravis (gMG), the therapy demonstrated statistically significant and clinically meaningful reductions in the risk of relapse compared with those on placebo from the external PREVENT trial (NCT01892345), a phase 3 study that evaluated eculizumab (Soliris; Alexion), an FDA-approved treatment for NMOSD.2
CHAMPION-NMOSD was an open-label, multicenter trial that evaluated the efficacy and safety of ravulizumab in patients with anti-AQP4 NMOSD who had at least 1 attack or relapse in the 12 months prior to the screening visit. These patients also had Expanded Disability Status Scale scores of 7 or less, had body weight of at least 40 kg at trial entry, and were allowed to stay on stable supportive immunosuppressive therapy for the duration of the trial. On day 1, patients received a single weight-based loading dose of ravulizumab, followed by regular weight-based maintenance dosing beginning on day 15, every 8 weeks.
The FDA approved ravulizumab for the treatment of gMG in early 2022, using findings from the phase 3 CHAMPION MG trial (NCT03920293) as the supporting data. Indicated for patients with gMG who are antiacetylcholine receptor-antibody positive, the approval was notable in several ways, as ravulizumab became the first approved long-acting C5 complement inhibitor for this patient population.3,4
In CHAMPION MG, treatment with ravulzumab resulted in rapid and sustained improvement of symptoms in patients with gMG for up to 26 weeks. At the end of the treatment period, investigators observed statistically significant differences in the primary end point of Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared with placebo (–3.1 vs 1.4; P <.001).