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Efgartigimod Was Well-Tolerated in Patients with Generalized Myasthenia Gravis

Efgartigimod was safe and effective for patients with generalized myasthenia gravis (MG), according to a phase 3, placebo controlled trial, presented at the virtual 2021 AAN Annual Meeting.

Efgartigimod, an investigational antibody fragment, is designed to block the activity of the neonatal Fc receptor, a protein that normally prevents IgG antibodies—including the harmful self-reactive antibodies found in MG patients — from being destroyed.

Efgartigimod was recently assessed in trials for efficacy in myasthenia gravis, said the study's lead author, James F. Howard Jr, MD, FAAN, professor of neurology at the University of North Carolina in Chapel Hill. “We are very excited that this offers a new option for our patients. It is a targeted therapy with a rapid onset of action, reasonable durability, and an acceptable side effect profile.

“The goal with this drug is not only to reduce disease burden, but also treatment burden for the patient, and in doing so, offer them a more normal and acceptable quality of life," he told Neurology Today At the Meetings.

If it meets regulatory approval standards in the US and abroad, this drug has the potential to revolutionize current myasthenia gravis management techniques, said Dr. Howard. “I believe that it will be a substitute for plasma exchange and intravenous immunoglobulin based on the side effect profiles," he said.

The study team assessed 38 patients who were AChR-antibody-negative (AChR-Ab-) and 129 who were AChR-Ab-positive (AChR+). Both groups were randomly assigned to either receive a placebo or an initial therapy cycle of four weekly 10 mg/kg infusions of efgartigimod. The researchers used a patient's Myasthenia Gravis Activities of Daily Living  (MG-DAL) score to determine subsequent therapy cycles.

About 68 percent of AChR-Ab+ patients were considered MG-DAL responders, meaning they had a two or more point improvement for four or more weeks following the first treatment cycle. This compared with only 29.7 percent of responders in patients receiving placebo.

Moreover, 63.1 percent of AChR-Ab+ treated patients were Quantitative Myasthenia Gravis (QMG) responders—meaning they had a three or more point improvement for four weeks or longer with the first treatment cycle—compared with 14.1 percent of placebo patients. 

The drug was also effective for 82.9 percent of QMG responders within the first two weeks and 84.1 percent of MG-ADL responders. Patients also had significant improvements in quality of life.

In AChR-Ab- patients, 21.1 percent of patients receiving placebo and 47.4 percent on efgartigimod reached both QMG and MG-ADL responder status.

Most adverse events were mild or moderate, and only a few cases were considered grade 3 severity.

“I'm not sure at this point whether it will play a role in myasthenic crisis for those who are hospitalized. We need further study for that," Dr. Howard said.

There are not many treatment options for myasthenia gravis, so it is very encouraging to have another alternative, said Alejandro Tobon, MD, chief of neurology at South Texas Veterans Healthcare System in San Antonio, who was not involved in the study. “The safety profile is going to be really important because the other available therapies have significant side effects, so more details looking into safety are key."

“Another aspect that is important to highlight is the quick response time [of this therapy], as some treatments for myasthenia may take months, especially the oral treatments. Having therapies that improve symptoms in two to four weeks is very promising," Dr. Tobon told Neurology Today At the Meetings.

“This is one of many FcRn receptor blockers that have been studied recently," added Michael H. Rivner, MD, FAAN, Charbonnier Professor Emeritus of Neurology at Augusta University in Georgia, who was not involved in the research. “This drug class is exciting because of the role played by FcRn receptors in recycling IgG."

Dr. Rivner said that other studies have considered a three-point increase in the MG-ADL to be significant. “So I wonder about the two-point increase used as their primary endpoint and would like to see their other results," Dr. Rivner told Neurology Today At the Meetings.

“This is an important class of drugs. It has the advantage of not being a blood product and probably will be superior to IVIg, but we will need more clinical experience to be certain," he added.

Dr. Howard has received personal compensation for serving as a consultant for Alexion Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Tobon did not report any disclosures. Dr. Rivner disclosed receiving an honorarium from Allergan and Alexion Pharmaceuticals. ​

Link Up for More Information

AAN Abstract. Howard J, Bril V, Vu T, et al. Efficacy, safety, and tolerability of efgartigimod in patients With generalized myasthenia gravis: Analysis of the phase 3 ADAPT study.