Japan Approves Vyvgart for Adults With Refractory gMG
Vyvgart will be available to generalized MG patients, regardless of antibody status, who are refractory, which means they have failed to respond to steroids or nonsteroidal immunosuppressive therapies.
The announcement comes on the heels of Vyvgart’s recent approval by the U.S. Food and Drug Administration (FDA) to treat adults with generalized MG who carry anti-acetylcholine receptor (AChR) antibodies, the most common type of MG-causing antibody. The therapy is also under review in Europe, with an approval decision expected in the second half of this year.
“People living with gMG around the world continue to experience severe disease burden despite treatment with commonly-used therapies,” Tim Van Hauwermeiren, CEO of Argenx, said in a press release. “Our commercial teams are ready and motivated to be serving as many people as possible who are living with this debilitating disease and we look forward to collaborating with the Japanese government to enable patient access.
“With today’s approval of Vyvgart in Japan, the recent U.S. FDA approval, and ongoing review of our application in Europe, we continue to advance rapidly toward achieving our goal of delivering this innovative, targeted treatment option globally,” Van Hauwermeiren added.
MG is characterized by debilitating muscle weakness caused by the immune system mistakenly producing antibodies that attack certain proteins essential for nerve-muscle communication. Generalized MG is a more severe form of the disease, whereby patients may experience weakness in multiple muscle groups.
Vyvgart is designed to block the neonatal Fc receptor (FcRn), a protein that normally protects antibodies circulating in the bloodstream from degradation. By blocking FcRn, the therapy aims to lower the levels of disease-driving antibodies.
“We are extremely proud to deliver the first-and-only approved FcRn blocker in Japan to a broad population of gMG patients, regardless of antibody status,” Van Hauwermeiren noted.
Argenx’s approval was backed by data from the Phase 3 ADAPT trial (NCT03669588) that assessed Vyvgart’s efficacy and safety in 167 adults with generalized MG, including 129 who were positive for anti-AChR antibodies.
In addition to their current standard treatments, participants were randomly assigned to receive 10 mg/kg of Vyvgart, administered by weekly infusion over four weeks, with a maximum of three treatment cycles — or a placebo — for 26 weeks (about six months).
Meeting the trial’s primary objective, more than half of anti-AChR antibody-positive patients treated with Vyvgart responded to treatment compared with placebo (68% vs. 30%). Treatment response was defined as a two-point (or more) sustained reduction on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, a standardized measure of MG symptom severity.
Vyvgart was also superior to placebo among participants who did not test positive for anti-AChR antibodies.
Based on the Quantitative Myasthenia Gravis (QMG) scale to quantify disease severity, there were significantly more responders — defined as those experiencing a minimum sustained reduction of three points on the QMG score — among patients treated with Vyvgart compared with placebo (63% vs. 14%).
The percentage of adverse events was similar in Vyvgart-treated participants and in those given a placebo. The most common side effects in ADAPT were headache (32% vs. 29% placebo), respiratory tract infection (33% vs. 29% placebo), and urinary tract infection (10% vs. 5% placebo).
Almost all ADAPT participants (90%) chose to enter the open-label extension study ADAPT+ (NCT03770403) to continue treatment with Vyvgart for up to three years. Long-term safety and tolerability data from ADAPT+ are expected in mid-2023.