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More patients with myasthenia gravis who were treated with the investigational agent efgartigimod achieved a sustained improvement in a scale of activities of daily living compared with patients who were given placebo, a researcher reported.

Of patients with generalized myasthenia gravis and anti-acetylcholine receptor antibody (AChR-Ab) positivity in a phase III study, 67.7% receiving efgartigimod achieved at least a 2-point improvement in their Myasthenia Gravis-Activities of Daily Living (MG-ADL) score after the first cycle of treatment, compared with 29.7% of those receiving placebo (P<0.0001), reported James Howard, MD, of the University of North Carolina School of Medicine in Chapel Hill.

"About 84% of the patients who responded to treatment did so in the first 2 weeks of treatment," Howard noted in his oral presentation at the American Academy of Neurology virtual meeting.

Additionally, 40% of the patients who received efgartigimod achieved at least a 6-point improvement in the MG-ADL score compared with just 8% of patients in the placebo arm.

Efgartigimod attacks the neonatal Fc receptor (FcRn) molecular pathway, said Howard. "It is a recycling mechanism for IgG, extending its half-life and serum concentration. Efgartigimod is a human IgG1 antibody Fc fragment, a natural ligand of FcRn that is engineered for increased affinity to FcRn. It was designed to outcompete endogenous IgG, thereby preventing recycling and promoting IgG lysosomal degradation."

In order to be eligible for the randomized, multicenter ADAPT study, patients had to have a baseline score of at least 5 points on the MG-ADL. Of the patients on efgartigimod, 40% achieved a score of 0-1, indicating minimal or no symptoms of disease.

ADAPT enrolled 167 patients who were diagnosed with class II, class III, or class IV criteria of the Myasthenia Gravis Foundation of America. The primary endpoint was an improvement of at least 2 points in MG-ADL score that was maintained for at least four consecutive weeks.

Patients were randomized 1:1 to receive an initial treatment cycle of four weekly infusions of efgartigimod (10 mg/kg) or placebo, and were stratified based on whether they were AChR-Ab-positive or negative, with 80% being positive.

The 84 patients receiving efgartigimod had a mean age of 45.9 and about 75% were women, while the 83 patients assigned to placebo had a mean age of 48.2 and 66.3% were women. The efgartigimod patients had been diagnosed with myasthenia gravis for about ten years, and the placebo patients for about nine years. The mean baseline score of the MG-ADL in the patients on efgartigimod was 9.2, and was 8.8 in the placebo patients.

Among the AChR-Ab-positive patients who achieved the primary endpoint, 34% had a sustained improvement for more than 12 weeks after the first cycle of therapy. More than half the patients had sustained duration of improvement for more than eight weeks, Howard noted.

Seven of 19 patients who failed to achieve a response in cycle 1 were able to respond when they were retreated in cycle 2.

After cycle 2, 70.6% of AChR-Ab-positive patients achieved the primary endpoint, compared with 25.6% of patients on placebo (P<0.0001).

"Although there are several available treatments for myasthenia gravis, many of them are associated with significant side effects that limit their use. There remains a need for new, effective treatments with a favorable side effect profile," Sami Saba, MD, of Lenox Hill Hospital/Hofstra Northwell School of Medicine in New York City, told 木瓜直播.

In ADAPT, adverse events were similar between groups. Serious adverse events were seen more often among placebo patients. Infusion-related reactions were rare, and were more common among the placebo patients, Howard reported.

"Therefore, this study is important in demonstrating efficacy in improving the symptoms of myasthenia gravis, while having a low risk of serious adverse effects," said Saba, who was not involved in the study.

"Furthermore, many of the treatments currently used don't take effect for weeks or months, while this treatment appears to have its effect within the first two weeks," he added. "For these reasons I do believe this treatment, if approved, will be sought out by both patients and clinicians."

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