RARE Daily

FDA Approves AstraZeneca’s Ultomiris for Adults with Generalized Myasthenia Gravis

April 28, 2022

The U.S. Food and Drug Administration approved AstraZeneca’s Alexion Rare Diseases’ Ultomiris for the treatment of adult patients with generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, which represents 80 percent of people living with the disease.

Photo: Marc Dunoyer, CEO of Alexion

Photo: Marc Dunoyer, CEO of Alexion

This FDA action marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of generalized myasthenia gravis (gMG).

“Ultomiris, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms,” said Marc Dunoyer, CEO of Alexion. “Ultomiris has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to Soliris every two weeks.”

Generalized myasthenia gravis (gMG) is a rare, debilitating, chronic, autoimmune neuromuscular disease characterized by loss of muscle function and severe muscle weakness. Eighty percent of people with gMG are AChR antibody positive meaning they produce specific antibodies (anti-AChR) that bind to signal receptors at the neuromuscular junction (NMJ), the connection point between nerve cells and the muscles they control. This binding activates the complement system, which is essential to the body’s defense against infection, causing the immune system to attack the NMJ, which leads to inflammation and a breakdown in communication between the brain and the muscles. gMG can occur at any age, but it most commonly begins for women before the age of 40 and for men after the age of 60. Initial symptoms may include slurred speech, double vision, droopy eyelids, and lack of balance; these can often lead to more severe symptoms as the disease progresses such as, impaired swallowing, choking, extreme fatigue and respiratory failure.

The FDA approval was based on positive results from the global, randomized, placebo-controlled CHAMPION-MG phase 3 trial, which showed early effect and lasting improvement in activities of daily living with the potential to reduce treatment burden with dosing every 8 weeks.

The trial enrolled 175 patients across North America, Europe, Asia-Pacific, and Japan. Participants were required to have a confirmed myasthenia gravis diagnosis at least six months prior to the screening visit with a positive serologic test for anti-AChR antibodies, MG-ADL total score of at least 6 at trial entry and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening. Patients could stay on stable standard of care medicines, with a few exceptions, for the duration of the randomized control period.

Patients were randomized 1:1 to receive Ultomiris or placebo for a total of 26 weeks. Patients received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint of change from baseline in the MG-ADL total score at Week 26 was assessed along with multiple secondary endpoints evaluating improvement in disease-related and quality-of-life measures. Ultomiris was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.

Patients who completed the randomized control period were eligible to continue into an open-label extension period evaluating the safety and efficacy of Ultomiris, which is ongoing.

“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 James Howard, Jr., Department of Neurology at The University of North Carolina School of Medicine and lead primary investigator in the CHAMPION-MG trial.

In the trial, the safety profile of Ultomiris was comparable to placebo and consistent with that observed in phase 3 trials of Ultomiris in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The most common adverse reactions in patients receiving Ultomiris were upper respiratory tract infection and diarrhea.

Regulatory submissions for Ultomiris for the treatment of gMG are currently under review with multiple health authorities, including in the European Union and Japan.

Ultomiris is also approved in the U.S., EU and Japan for the treatment of certain adults and children with PNH, and for certain adults and children with aHUS to inhibit complement-mediated thrombotic microangiopathy.

Author: Rare Daily Staff

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