The approval is supported by phase 3 data which showed statistically significant differences on MG-ADL and QMG scores relative to placebo following 26 weeks of treatment.
The FDA has approved ravulizumab (Ultomiris; Alexion), a terminal compliment C5 inhibitor, for the treatment of patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. With the decision, ravulizumab becomes the first approved long-acting C5 complement inhibitor for this patient population.1
The approval was based on data from the phase 3 CHAMPION MG trial (NCT03920293), in which treatment with ravulizumab 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 improvements on 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).2
Primary investigator James F. Howard, MD, distinguished professor of neuromuscular disease, University of North Carolina School of Medicine, said in a statement that, “despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy."1
Results from CHAMPION-MG were recently published in the New England Journal of Medicine Evidence and presented at the 2022 American Academy of Neurology Annual Meeting. In this phase 3, double-blind study, patients on the study drug received body weight-based doses of 2400 to 3000 mg induction on day 1, then 3000 to 3600 mg every 8 weeks on day 15. Patients had AChR antibody positive gMG and were allowed to be on stable-dose AChR and immunosuppressant therapy throughout the study.
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Change in Quantitative Myasthenia Gravis (QMG) total scores, a secondary end point, showed statistically significant improvements following ravulizumab treatment compared with placebo (P <.001). The least squares estimate of the mean QMG change was –2.8 (95% CI, –3.7 to –1.9) in the ravulizumab group and –0.8 (95% CI, –1.7 to 0.1) in the placebo group (P <.001). QMG total scores improved by 5 points or more in a significantly greater proportion of ravulizumab-treated patients than of those receiving placebo (30.0% vs 11.3%; P = .005).2
"gMG takes a physical and emotional toll on those living with the disease. We are grateful for continued innovation and research into new treatment and dosing options to meet the needs of more patients and reduce the treatment burden," Samantha Masterson, chief executive officer, Myasthenia Gravis Foundation of America, said in a statement.1 "With the approval of ULTOMIRIS, we’re excited that MG patients now have another option to consider as part of their personalized treatment strategies that may offer more convenience and improve muscle weakness."
In CHAMPION-MG, the proportion of patients who experienced adverse events (AEs) or AEs related to the study drug were similar between the treatment groups. There were no notable differences in the types of AEs, with the most frequent event being headache, experienced by 16 patients (19%) in the ravulizumab group and 23 (26%) in the placebo group. Serious AEs were reported in 23% and 16% in the ravulizumab and placebo groups, respectively, the most frequent of which were related to worsening of MG and COVID-19. Two serious AEs (dysphasia and tendonitis) in 2 ravulizumab-treated patients and 4 (cellulitis [2 cases], herpes zoster infection, and infusion-related reaction) serious AEs occurred in the placebo group and were considered treatment-related.
"Since bringing forward the first complement inhibitor, we’ve continued to listen to the community and focused innovation on the needs of gMG patients," Marc Dunoyer, chief executive officer, Alexion, said in a statement.1 "We’re proud to deliver on this commitment with today’s approval. ULTOMIRIS, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms.”
Ravulizumab is currently approved in the US for the treatment of adults and children 1 month and older with paroxysmal nocturnal hemoglobinuria. It is also approved in the US and Japan for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy in adult and pediatric patients, as well as in the European Union for the treatment of adults and children with a body weight of at least 10 kg with aHUS.