FDA Approves Vyvgart for Adults With Most Common Form of gMG
Vyvgart (efgartigimod) has been approved by the U.S. Food and Drug Administration (FDA) to treat adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive, the therapy’s developer, Argenx, announced.
According to Argenx, this patient group represents about 85% of all with generalized MG.
“Today is the start of a new era for argenx and the gMG community as we honor our commitment to bring forward an innovative treatment option for people living with this debilitating disease,” Tim Van Hauwermeiren, CEO of Argenx, said in a company press release. “The approval of Vyvgart represents many achievements: our first approved product; the first-and-only FDA-approved neonatal Fc receptor blocker; and the first approved therapy designed to reduce pathogenic IgGs, an underlying driver of gMG.”
Samantha Masterson, president and CEO of the Myasthenia Gravis Foundation of America, added: “The gMG community has long-awaited the FDA approval of Vyvgart, especially for those patients who struggle with basic personal tasks such as speaking, chewing and swallowing food, brushing teeth and hair, and in some severe cases, breathing. We thank argenx for its continued commitment to the gMG patient community, which led them to deliver this much-needed new treatment option with the potential to change the lives of many gMG patients.”
A decision on efgartigimod’s approval in Europe is expected by mid-2022. The therapy is also under review by regulators in Japan, and Argenx’s partner Zai Lab is planning to seek approval in China soon.
MG is caused by the body’s immune system erroneously attacking healthy muscle cells, with attacks driven by proteins called antibodies.
Vyvgart is designed to block the activity of a protein called the neonatal Fc receptor (FcRn), which normally helps protect certain antibodies from being broken down. By blocking FcRn, the therapy works to lower levels of disease-driving antibodies.
Argenx’s request for approval was supported by data from the Phase 3 ADAPT (NCT03669588) trial that evaluated efgartigimod’s safety and efficacy in 167 adults with generalized MG. Of this group, 129 patients were positive for antibodies against the acetylcholine receptor (anti-AChR antibodies), the most common type of MG-causing antibody.
Trial participants were given Vyvgart (10 mg/kg) or a placebo for 26 weeks (about six months). The treatment was administered in single weekly infusion cycles over four weeks, with a maximum of three rounds of treatment over the study’s course.
Additional analyses showed that more than half of anti-AChR antibody-positive patients given Vyvgart (68% according to the latest data) responded to the treatment, defined as a two-point or greater drop on the Myasthenia Gravis Activities of Daily Living (MG-ADL), a standardized measure of MG symptoms severity. Their response was sustained for at least one month after a first treatment round.
Most ADAPT patients (90%) chose to continue or start treatment in its open-label extension study, called ADAPT+ (NCT03770403), evaluating the long-term safety and tolerability of Vyvgart. ADAPT+ is due to end in June 2023.
Rates of adverse events were similar among treated adults and those on a placebo. Vyvgart’s most common side effects (affecting 10% or more of patients) are respiratory tract infections, headache, and urinary tract infection.
“The approval of Vyvgart is a significant step forward toward treating gMG, a disease that, up until a few years ago, had no approved therapies,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in its release. “Now those living with AChR ab+ gMG will have the choice of another effective disease modifying therapeutic.”
Soliris (eculizumab), by Alexion Pharmaceuticals, was approved as an infusion treatment for anti-AChR antibody-positive gMG adults in Europe and the U.S. in 2017. It works by blocking part of the immune system called the terminal complement cascade.
Vyvgart is soon expected to be available in the U.S., Argenx stated in its release.
While its U.S. list price was not disclosed, the company reported having “reached agreements in principle with several national and regional commercial payers to structure a value-based agreement. The agreements are meant to provide predictability of cost for payers and appropriate access for patients.”
“Generalized myasthenia gravis … affects each patient differently which can create variability in dosing and the resulting cost per patient,” said Steve Miller, MD, executive vice president and chief clinical officer at Cigna, a global health service company collaborating with Argenx for the launch of Vyvgart.
“Argenx has put forth an innovative, value-based approach to contracting that will help payers with cost predictability as they face the challenge of ensuring real-world dosing remains affordable. This was a direct result of early engagement between argenx and Evernorth [Cigna’s health services division] leading up to approval,” Miller added.
A recent analysis by the Institute for Clinical and Economic Review (ICER) — a nonprofit group that assesses the costs and benefits of medications in the U.S. — estimated that efgartigimod would be cost-effective at $18,300–$28,400 per year.
In order to support affordable access to Vyvgart, Argenx is launching “My Vyvgart Path,” a program that offers patients and clinicians support, product education, and financial assistance information, among other resources.