Japan Approves AstraZeneca’s Complement Inhibitor For Rare Muscle Disorder

AstraZeneca has announced the approval of Ultomiris (ravulizumab) in Japan to treat adult patients with generalized myasthenia gravis (gMG), a rare autoimmune disorder that causes muscle weakness. 

A C5 complement inhibitor, Ultomiris is indicated for gMG patients who test positive for anti-acetylcholine (AChR) antibody and whose symptoms are hard to control with intravenous immunoglobulin therapy (IVIg) or plasmapheresis. Japan’s regulator has also indicated that the treatment may be considered for patients who cannot receive high-dose IVIg or plasmapheresis due to complications. 

What Is Myasthenia Gravis (gMG)?

Most people with gMG (around 80%) produce anti-AChR antibodies that bind to signal receptors in the connection point between nerve cells and the muscle cells they control. The binding activates the complement cascade, one of the body’s defenses against infection, causing the immune system to attack the connection point. This leads to inflammation and breakdown of communication between the brain and muscles, causing muscle weakness and loss of function. It is estimated that 22,000 people live with gMG in Japan. 

A Long-Acting C5 Complement Inhibitor

Ultomiris inhibits the C5 complement protein in the complement cascade to prevent the immune system from over-activating. The Japanese approval for Ultomiris is based on results from its global Phase 3 study, Champion-MG, which showed that the drug was superior to placebo in enhancing the patients’ abilities to perform daily activities. Long-lasting clinical benefits from the drug were observed in an extended follow up lasting through 60 weeks. 

“The approval of Ultomiris is an important advance for the gMG community in Japan, offering patients and physicians a new long-acting C5 inhibitor that has demonstrated sustained improvement in activities of daily living through 60 weeks, with fewer infusions per year over current treatment,” said Hiroyuki Murai, MD, PhD, Professor and Chairman, Department of Neurology, School of Medicine, International University of Health and Welfare, Narita, Japan. 

In Champion-MG, the safety profile of Ultomiris was comparable to placebo and consistent with safety results from the drug’s Phase 3 trials in paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS), two other indications it has been approved of. Common side effects of Ultomiris include nausea, headache and diarrhoea.

Results from the Champion-MG trial were published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting in April.

The Japanese approval follows a similar nod from the US FDA in April for Ultomiris for anti-AChR antibody-positive gMG. In Europe, an approval for the same indication seems likely as the drug was recently recommended as an add-on to standard therapy for anti-AChR-positive gMG.

Besides gMG, Ultomiris is approved in the US, the EU and Japan for certain patients with PNH or aHUS, and is being investigated in additional hematology and neurology indications. 

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Joy Lin

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