Argenx’s antibody fragment to target the neonatal Fc receptor is the first in its class, with its approval backed by data from the phase 3 ADAPT trial.
The FDA has approved Argenx’s first-in-class investigational antibody fragment to target the neonatal Fc receptor (FcRn), efgartigimod, for the treatment of generalized myasthenia gravis (gMG) in adults who test positive for the anti-acetylcholine receptor (AChR) antibody, according to an announcement.1
The drug will now be marketed as Vyvgart. The agency had previously granted the therapy both fast track and orphan drug designations. Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a statement that the approval "is an important step in providing a novel therapy option for patients and underscores the agency’s commitment to help make new treatment options available for people living with rare diseases.”
"The approval of efgartigimod by the FDA is going to again transform our management of myasthenia gravis, without question. The ability of this drug to reduce levels of circulating antibody IgG will provide patients with a new option for therapy, a much safer option for therapy, and one that has been demonstrated in clinical trials to be of substantial durability in its duration of effect," clinical trial investigator James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, University of North Carolina School of Medicine, told NeurologyLive®.
"My prediction will be that the use of both plasma exchange and intravenous, and perhaps subcutaneous, immunoglobulin will be markedly lessened, if not completely replaced, primarily based not only on the efficacy but the safety of this product. The adverse event profiles are very similar between placebo and treated arm, and the safety alone that it offers is something that will move clinicians to begin using this drug," Howard said, adding that the agent also offers an advantage logistically in that it will allow patients to forego trips to a facility to have plasma exchange in favor of in-home infusions.
"It's all about patient choice," he explained. "Patients want independence, and the ADAPT trial was designed to demonstrate independence, as well as efficacy, and efgartigimod scored high on both counts. I see this as a huge player."
The biologics license application (BLA) submitted to the agency was supported by data from the phase 3 ADAPT trial (NCT03669588).2 All told, 167 patients were randomized to an evaluation arm in the ADAPT trial, 84 who were randomized to the efgartigimod group and 83 to the placebo group. Of the full population, 77% (n = 129) were acetylcholine receptor-antibody positive (AChR-Ab+).
The findings of that study suggest that efgartigimod was well-tolerated and efficacious in treating patients with gMG, with the drug meeting the primary end point by improving gMG activities of daily living (MG-ADL) scores for patients with AChR-Ab+ gMG compared with those in the placebo group (67.7% vs. 29.7%; P <.0001). Additionally, 40.0% of efgartigimod-treated AChR-Ab+ patients achieved minimal or no symptoms compared with 11.1% treated with placebo.3
Howard, who was the study's lead author, also spoke with NeurologyLive® in June 2021 to share his perspectives on the full dataset. He discussed some of the unique findings of the analysis, the potential of this agent, and his experience with the drug in its clinical development.
“What we also saw was that those who were AChR, MUSK, LRP4, triple-negative patients had similar responses,” he told NeurologyLive® at the time of the full data release in June. “Now, their numbers are very small; they only represented 20% of the population—and that’s still undergoing analysis—but on the surface, they look to have similar responses as the larger population.”
A list of secondary end points that demonstrated significant differences in the efgartigimod arm for AChR-Ab+ patients compared with placebo include MG-ADL responders in the overall population, as well as both AChR-Ab+ and AChR– patients (P <.0001), and time on trial in clinically meaningful improvement, defined as an MG-ADL improvement of 2 points or greater (P = .0001). Additional significant differences from efgartigimod group for AChR-Ab+ patients compared with placebo were fast onset of response on MG-ADL score, defined as onset observed in first 2 weeks (P = .0004).3,4
A sustained response was observed in 88.6% AChR-Ab+ patients who met the primary end point for at least 6 weeks, 56.8% for at least 8 weeks, and 34.1% for at least 12 weeks. Furthermore, 70.6% of AChR-Ab+ patients received a second treatment cycle, compared to only 25.6% of placebo patients.3,4
Of those in the treatment group 77% (n = 65) experienced treatment-emergent adverse events (AEs), while and 84% (n = 70) of the placebo group did. The most frequent AEs reported were headache (efgartigimod: 29% [n = 24]; placebo: 28% [n = 23]) and nasopharyngitis (efgartigimod: 12% [n = 10]; placebo: 18% [n = 15]). Five percent (n = 4) of efgartigimod-treated patients and 8% (n = 7) patients in the placebo group had a serious AE, and each group had 3 patients (4%) discontinue treatment during the study.3
“The other thing that was very gratifying was the safety profile. It was very nominal and much like those who were in the placebo arm of the study… The infusion reactions were the same—in fact, more in the placebo arm than in the drug arm, so that was very gratifying as well. What we’re seeing is a very rapidly acting drug with, albeit variable, but fairly prolonged, duration of action with a very nominal [adverse] effect profile,” Howard said.
An open-label extension trial of the therapy is ongoing, called ADAPT+ (NCT03770403), and there are plans to explore a potential subcutaneous administration of the agent in addition to its current intravenous infusion formulation.