FDA Grants Argenx Priority Review for Under-the-skin Efgartigimod
Treatment candidate contains active ingredient of Vyvgart, approved for gMG
The U.S. Food and Drug Administration (FDA) has granted priority review to Argenx’s under-the-skin (subcutaneous) formulation of efgartigimod — the active ingredient in Vyvgart, the company’s approved treatment for generalized myasthenia gravis (gMG).
If the subcutaneous formulation wins regulatory approval following that review, it would broaden the delivery options for efgartigimod, now given as an intravenous (into-the-blood) infusion under the brand name Vyvgart.
The decision to grant priority review comes following the company’s submission of a biologics license application (BLA) seeking the approval of subcutaneous efgartigimod in the U.S. A priority review sets an FDA action date on the application within six months, bringing the review time down from the standard period of 10 months.
Here, the Prescription Drug User Fee Act (PDUFA) target action date — the date by which the FDA must announce its decision on whether or not to approve the therapy — was set for March 20, 2023.
“With an established PDUFA date, we are preparing for our second commercial product launch and look forward to potentially bringing forth another first-in-class option for gMG patients,” Keith Woods, chief operating officer of Argenx, said in a press release.
Argenx seeks new delivery method for efgartigimod
“The FDA’s acceptance of our BLA is an exciting step toward fulfilling our vision of delivering the broadest gMG treatment offering that reflects the unique disease experience for each patient as they navigate life with this debilitating disease,” Woods said.
Approved by the FDA in 2021, Vyvgart is administered via hour-long infusions into the bloodstream. It is indicated for the treatment of gMG in adults who are positive for anti-acetylcholine receptor (AChR) antibodies, which are the most common type of MG-causing self-reactive antibodies.
The medication works by blocking a protein called neonatal Fc receptor (FcRn), which attaches to these antibodies, stabilizing them and preventing their degradation. By blocking FcRn, Vyvgart increases the rate at which these antibodies are broken down, lowering their levels in the body. This is expected to ease muscle weakness, fatigue, and other symptoms of gMG.
The subcutaneous formulation is meant to be administered using Halozyme’s Enhanze delivery technology. This tech uses a lab-made version of the human hyaluronidase PH20 protein to temporarily remove a gel-like substance that forms under the skin and works as a barrier to fluid flow.
Using Enhanze is expected to facilitate the delivery of biologic therapies that are typically administered by infusion directly into the bloodstream.
“We’re excited about the potential of [subcutaneous] efgartigimod to offer patients multiple ways to receive treatment through various administrations and an individualized dosing schedule,” Woods said.
Argenx’s BLA was backed by data from a Phase 3 clinical trial called ADAPT-SC (NCT04735432). The study included 110 people with gMG in North America, Europe, and Japan. The majority tested positive for anti-AChR antibodies, but there also were patients in whom anti-AChR antibodies were not detected.
At study entry, participants were randomly assigned to receive either 1,000 mg of subcutaneous efgartigimod or Vyvgart (10 mg/kg), given once per week, for four weeks.
Data showed that the reduction in total immunoglobulin G (IgG) — a type of antibodies implicated in MG — was similar in both groups after 29 days of treatment (66.4% vs. 62.2%). This means that subcutaneous efgartigimod was not worse than Vyvgart.
The effect was similar regardless of whether patients were positive for anti-AChR antibodies or not.
More than two-thirds (69.1%) of patients on under-the-skin efgartigimod experienced a clinically significant improvement — of a minimum of two points for at least four consecutive weeks, or about one month — on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. The MG-ADL measures the disease’s impact on daily life.
About as many patients (65.5%) improved by at least three points on the Quantitative Myasthenia Gravis (QMG) score, another measure of disease severity, for four consecutive weeks.
More than one-third of patients (37%) achieved minimal symptom expression (MSE), which means they had mild or no symptoms, after one cycle of treatment with subcutaneous efgartigimod.
The experimental treatment was generally well-tolerated among patients. The most common side effects were injection site reactions, which were mild or moderate in severity, and resolved with time.
After completing ADAPT-SC, most participants (95%) rolled over into ADAPT-SC+ (NCT04818671), an open-label extension study that will continue treatment for up to two years. The study is evaluating the long-term safety and tolerability of subcutaneous efgartigimod when given over three-week periods and repeated as needed with at least 28 days of interval.