New Phase 3 Trial Data Support Efficacy of Efgartigimod for Generalized MG

Treatment with Argenx‘s investigational therapy efgartigimod leads to significant and early reductions in the severity of generalized myasthenia gravis (gMG), regardless of the presence of antibodies against acetylcholine receptor (AChR), according to results from a Phase 3 clinical trial.

Trial findings were presented earlier this month at the Myasthenia Gravis Foundation of America 2020 Virtual Scientific Session.

“These new data on the magnitude and repeatability of response continue to support the potential of efgartigimod as a meaningful treatment for gMG patients,” Wim Parys, MD, Argenx’s chief medical officer, said in a press release.

According to the company, it remains on track to submit an application seeking efgartigimod’s approval to the U.S. Food and Drug Administration by the end of the year.

MG is caused by the immune system targeting the body’s healthy muscle cells. This immunological attack is driven by a type of antibody called immunoglobulin G (IgG). Most commonly, MG-driving autoantibodies specifically target the AChR protein, impairing the communication between nerve endings and muscle cells.

Efgartigimod is designed to block the activity of a protein known as neonatal Fc receptor. This protein normally prevents IgG from breaking down. By blocking it, efgartigimod is expected to decrease levels of IgG in the body.

The Phase 3 ADAPT trial (NCT03669588), sponsored by Argenx, tested the safety and effectiveness of efgartigimod in 167 adults with gMG. Of these participants, 129 were positive for antibodies against AChR, and about two-thirds were women.

Participants were randomly assigned to either 10 mg/kg of efgartigimod (mean age 14.4) or a placebo (mean age 15), infused directly into the bloodstream, for 26 weeks, or nearly six months. Efgartigimod was given in addition to the patients’ ongoing treatments. For the first four weeks, participants received weekly infusions, after which treatment schedules were individualized based on each participant’s clinical response.

To measure treatment efficacy, participants in the trial regularly filled out two standardized questionnaires that measure the severity of MG symptoms: the Myasthenia Gravis Activities of Daily Living (MG-ADL) and the Quantitative MG (QMG).

For the purposes of the trial, participants were deemed “responders” on the MG-ADL if they experienced a two-point improvement lasting at least four weeks. Responders on the QMG experienced a minimum three-point improvement over at least the same period.

Previously reported top-line results showed that, compared with the placebo group, significantly more anti-AChR-positive participants given efgartigimod were responders, based on both the MG-ADL (67.7% vs. 29.7%) and the QMG (63.1% vs. 14.1%), supporting the therapy’s efficacy. The therapy was well tolerated, with a similar frequency of adverse events reported by participants on efgartigimod or the placebo.

“Efgartigimod demonstrated in ADAPT that it is well-tolerated and that patients can experience clinically meaningful improvements in key measures of function and strength following treatment, including, in some, the achievement of minimal symptom expression,” said James F. Howard Jr., MD, a professor at the University of North Carolina at Chapel Hill School of Medicine and principal investigator of the ADAPT trial.

The newly reported results shed further light on the magnitude of the experimental treatment’s effect. After four weeks, 55.6% of the anti-AChR-positive participants treated with efgartigimod experienced a five-point or more improvement on the MG-ADL score, and 50% saw a six-point or more improvement on the QMG score. Substantially fewer participants given a placebo experienced such improvements — 11.7% for MG-ADL and 5.2% for QMG.

About a third (33.9%) of efgartigimod-treated participants experienced a QMG improvement of nine points, a benefit not seen with the placebo.

In addition, among anti-AChR-positive participants, the proportion of responders was similar after the first and second treatment cycles. Significantly more participants given efgartigimod than a placebo were responders after the first (67.7% vs. 29.7%) and second (70.6% vs. 25.6%) cycles, illustrating the repeatability of the treatment response.

A subsequent analysis indicated that nine (47.4%) AChR-negative participants given efgartigimod were responders on both the MG-ADL and QMG, compared with four (21.1%) AChR-negative participants on the placebo.

Data indicate that efgartigimod does decrease IgG levels: In anti-AChR-positive participants, total IgG levels decreased by a mean maximum of 61.3% after four weeks, and levels of anti-AChR antibodies lowered by 57.6%. Similar overall IgG results were seen in AChR-negative individuals.

“These exciting results suggest that efgartigimod as a new potential therapy for gMG could have a real impact on some of the daily limitations that patients face,” Howard said.