The US Food and Drug Administration (FDA) has accepted and placed on priority review an application for approval of Ultomiris (ravulizumab-cwvz) to treat adults with generalized myasthenia gravis (gMG).
The FDA has set April through June as the target date for its decision.
Ultomiris is a monoclonal antibody designed to block activation of the complement cascade, a part of the immune system believed to drive gMG.
Developed by Alexion Pharmaceuticals, now part of AstraZeneca, it is the company’s second complement antibody. Soliris (eculizumab), the first, is approved to treat gMG in adults who test positive for anti-acetylcholine receptor (AChR) antibodies in the United States, Europe and Japan.
“Soliris was the first new treatment approved for this devastating disease in approximately 60 years, and this case for Ultomiris demonstrates Alexion’s continued commitment to improving outcomes for patients with gMG,” said Marc Dunoyer, CEO of Alexion, in a press release.
The claim is supported by data from the phase 3 CHAMPION MG trial (NCT03920293), which evaluated the safety and efficacy of Ultomiris compared to placebo in 175 adults with gMG and without prior inhibitor therapy. of the complement.
Patients were randomized to receive Ultomiris or placebo for 26 weeks (approximately six months). Those who have completed this randomized trial phase could join its ongoing, open-label extension study, and continue or start receiving Ultomiris for up to two years.
The primary goal of CHAMPION MG was to modify the activities of daily living in MG (MG-ADL), a validated measure of the severity of MG reported by patients from study start through week 26.
All included patients were positive for antibodies targeting the acetylcholine receptor, the most common cause of MG, and their mean total MG-ADL score was 9 (range 6 to 24) at the start of the study, a benchmark measurement. Most were white (73%), with an average age of 55.6 years, and about half were female.
Ultomiris was administered by infusion into the bloodstream every eight weeks after an initial loading dose in the trial. Soliris, on the other hand, is given as an infusion every two weeks after an initial loading dose, and its FDA label carries a black-boxed warning of a risk of potentially fatal meningococcal bacterial infection.
The trial achieved its primary goal, with results showing that patients treated with Ultomiris had a statistically significant drop in MG-ADL scores – by 3.1 points on average – compared to those on placebo, whose scores fell. an average of 1.4 points at 26 weeks. The benefits of treatment, as reflected in MG-ADL scores, were seen as early as one week after starting treatment.
The Quantitative Myasthenia Gravis (QMG) score, a clinician-reported measure of disease severity, also confirmed the benefits of Ultomiris, with three times as many patients showing at least a five-point decrease in QMG score, indicating marked improvements.
“The Phase III trial shows that Ultomiris can help a wider range of patients, including those with milder symptoms or who are earlier in their treatment journey,” Dunoyer said.
Benefits were maintained for up to 52 weeks in patients in the main trial who completed 26 weeks of treatment in its extension study, and no cases of meningococcal infection were observed during this extended period. , Alexion reported.
Measures to assess fatigue and health-related quality of life generally showed trends in favor of Ultomiris over placebo, but these differences were not statistically significant.
Safety data was consistent with Phase 3 studies of Ultomiris in other disorders, with the most common side effects being headache, diarrhea and nausea. Serious adverse events were reported in two patients on Ultomiris and four on placebo, and two patients on Ultomiris died during the trial – one due to COVID-19 and the other after a brain hemorrhage or bleeding in the brain.
Regulators in the European Union and Japan are currently reviewing similar applications for approval of Ultomiris in the treatment of gMG.
Ultomiris is approved to treat atypical hemolytic uraemic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH) in the United States, Europe and elsewhere. These two rare diseases are characterized by abnormal activation of the complement system, leading to excessive destruction of red blood cells.