FDA Approves Ravulizumab-cwvz for Generalized Myasthenia Gravis

The FDA has approved ravulizumab-cwvz (Ultomiris; Alexion, AstraZeneca) for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. Ravulizumab-cwvz is now the first and only long-acting C5 complement inhibitor for the treatment of gMG to gain FDA approval.

Approximately 80% of patients with gMG are AChR antibody-positive, according to AstraZeneca. gMG is a rare, chronic, autoimmune neuromuscular disease that causes a loss of muscle function and severe weakness.

“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,” said Samantha Masterson, chief executive officer, Myasthenia Gravis Foundation of America (MGFA), in a press release. “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.”

Ravulizumab-cwvz works by inhibiting the C5 protein in the terminal complement cascade, which when activated in an uncontrolled manner causes the body to attack its own healthy cells. The drug is administered intravenously every 8 weeks following a loading dose.

The FDA approval was based on positive findings from the phase 3 CHAMPION-MG trial, which found that ravulizumab-cwvz was superior to placebo in change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at week 26, a patient-reported scale assessing the ability to perform daily activities, which was the primary endpoint of the study.

“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,” said CHAMPION-MG trial lead primary investigator James F. Howard, Jr, MD, Department of Neurology at The University of North Carolina School of Medicine, in a press release.

CHAMPION-MG was a randomized, double-blind, placebo-controlled, multicenter 26-week trial that enrolled 175 patients across North America, Europe, Asia-Pacific, and Japan. Patients must have had a confirmed myasthenia gravis diagnosis at least 6 months before the screening visit with a positive serologic test for anti-AChR antibodies, MG-ADL total score of at least 6 at trial entry, and MGFA Clinical Classification Class II to IV at screening.

Patients were permitted to stay on stable standard of care treatments, with a few exceptions, for the duration of the randomized control period.

The investigators randomized the patients 1:1 to receive either a single weight-based loading dose of ravulizumab-cwvz followed by regular weight-based maintenance dosing beginning on day 15 every 8 weeks, or to receive placebo for a total of 26 weeks. The primary endpoint of change from baseline in the MG-ADL total score at week 26 was evaluated, with secondary endpoints measuring improvement in disease-related and quality-of-life measures.

The safety profile of ravulizumab-cwvz was comparable to placebo and consistent with what was previously observed in phase 3 trials of the drug in in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. The most common adverse events reported were upper respiratory tract infection and diarrhea.

Those who finished the randomized control period were eligible to continue into the ongoing open-label extension period to determine the safety and efficacy of ravulizumab-cwvz.

“Ultomiris, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms. As presented at the 2022 American Academy of Neurology Annual Meeting, Ultomiris has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to Soliris every two weeks,” said Marc Dunoyer, Alexion chief executive officer, in a press release.

Reference

Ultomiris approved in the US for adults with generalised myasthenia gravis. AstraZeneca. News release. April 27, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-approved-in-the-us-for-adults-with-generalised-myasthenia-gravis.html