AstraZeneca Announces Long-Term Efficacy of Ultomiris in Phase 3 CHAMPION-MG Trial for Generalized Myasthenia Gravis

Translation | newborn

Recently, AstraZeneca announced the long-term follow-up results from the open-label extension (OLE) phase of the Phase III CHAMPION-MG trial. The data showed that: Ultomiris (ravulizumab), a long-acting C5 complement inhibitor, demonstrated sustained efficacy in adult patients with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) antibodies. During the 60-week treatment period, patients experienced improvements in activities of daily living, muscle strength, and quality of life. Throughout the analysis, Ultomiris was well-tolerated.

gMG is a rare, debilitating chronic autoimmune neuromuscular disorder that can lead to loss of neuromuscular function and severe weakness. It is estimated that 85% of gMG patients are anti-AChR antibody positive. Ultomiris, a second-generation long-acting C5 complement inhibitor, was acquired by AstraZeneca in December 2020 for $39 billion through the acquisition of Alexion. It works by inhibiting the C5 protein in the terminal part of the complement cascade.

It is reported that Ultomiris has been approved for the treatment of two rare diseases: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Currently, the new indication application for Ultomiris in the treatment of gMG is under review by U.S. and EU regulatory agencies.

In the CHAMPION-MG trial, 99.4% of patients (n=161) entered the OLE after the 26-week Randomized Controlled Period (RCP), during which all patients received Ultomiris treatment. At the data cutoff, 113 patients had reached Week 60. The efficacy analysis included all patients who received ≥1 dose of Ultomiris during the OLE.

At OLE Week 60, there were statistically significant improvements in patient functional activity, muscle strength, and quality of life metrics compared to baseline (defined as the start of Ultomiris treatment), including the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score (-4.0 [95% CI: -4.8, -3.1], p<0.0001).

Moreover, patients transitioning from placebo (n=83) to Ultomiris treatment showed a rapid relief of similar degree and time course as those treated with Ultomiris during the RCP.

Specifically, for patients treated with Ultomiris for 60 weeks, the changes in scores on multiple scales relative to the RCP baseline are as follows:

During the OLE period of the CHAMPION-MG trial, the safety and tolerability of Ultomiris were consistent with the known safety profile of Ultomiris observed during the RCP period and in other approved indications. The most common adverse events (occurring in ≥10% of 169 patients treated with Ultomiris during the RCP and/or OLE periods) were headache (16.6%) and diarrhea (13.6%).

Reference Source: ULTOMIRIS (ravulizumab-cwvz) demonstrated sustained improvements in functional activities and quality of life in adults with generalized myasthenia gravis through 60 weeks