Efgartigimod as Injection Similar to Vyvgart in Treating gMG, Trial Finds
An under-the-skin injection formulation of efgartigimod is as effective as the therapy’s infusion version, sold as Vyvgart (efgartigimod alfa-fcab), at lowering immunoglobulin G antibody levels in people with generalized myasthenia gravis (gMG), according to top-line data from the ADAPT-SC trial.
Based on these findings, Argenx, the therapy’s developer, plans to apply to the U.S. Food and Drug Administration (FDA) by year’s end asking for approval of the new formulation.
“Every person living with gMG experiences the disease in their own way, including how they manage symptoms,” James Howard Jr., MD, the trial’s lead investigator and a neurology professor at the University of North Carolina at Chapel Hill School of Medicine, said in a press release. “For many years, patients lacked sufficient treatment options, let alone those that were tailored to their unique needs.”
Efgartigimod, the active ingredient in Vyvgart — administered via hourlong, intravenous (into-the-vein) infusions — is designed to lower the levels of the harmful self-reactive antibodies that drive MG.
Subcutaneous, or under-the-skin, efgartigimod is a re-formulated version of Vyvgart, developed using Halozyme Therapeutics’ drug delivery technology, which facilitates injectable delivery of biologic therapies that are typically administered by infusion into the bloodstream.
“We are excited for the potential of the subcutaneous form of efgartigimod to offer patients … an additional treatment option,” Helen Torley, president and CEO of Halozyme, said in a separate press release.
“We are pleased to see another partner generate strong pivotal trial results with a therapy utilizing our ENHANZE technology,” Torley added.
In the Phase 3 ADAPT-SC trial (NCT04735432), 110 adults with gMG in North America, Europe, and Japan were randomly assigned to either four weekly doses of efgartigimod as a 1,000 mg subcutaneous injection or Vyvgart at 10 mg/kg. Participants remained on a stable dose of at least one gMG treatment throughout.
The study met its primary goal by demonstrating that subcutaneous efgartigimod was similar, or noninferior, to Vyvgart at lowering mean total immunoglobulin G antibodies one week after the last dose (66.4% vs. 62.2%). Results were the same for patients with and without antibodies that selectively target acetylcholine receptors, the most common type of MG-causing antibodies.
In key secondary endpoints, 69.1% of patients given subcutaneous efgartigimod responded — defined by at least a two-point improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score for at least four consecutive weeks.
A three-point improvement or more on the Quantitative Myasthenia Gravis (QMG) score for at least four consecutive weeks was achieved by 65.5% of patients treated with efgartigimod as an under-the-skin injection. The onset of effect and minimal symptoms (an MG-ADL score between 0 and 1) were consistent with ADAPT (NCT03669588), the Phase 3 trial that supported Vyvgart’s approval in the U.S. and Japan.
The safety profile of subcutaneous efgartigimod was also consistent with ADAPT findings. The therapy was generally well-tolerated with mild to moderate injection site reactions being the most frequent adverse events, all of which resolved with time.
Detailed data from ADAPT-SC trial will be presented at a future medical meeting, Argenx said.
“Our goal is to redefine and deliver targeted treatment options for people living with gMG globally,” said Tim Van Hauwermeiren, CEO of Argenx. “By listening to the gMG community, we heard the importance of creating optionality and flexibility for patients.”
“We’re excited about the potential to deliver two best-in-class options that provide flexibility around route of administration and dosing schedule, and look forward to collaborating with the FDA to bring another innovative treatment option to people living with gMG,” Van Hauwermeiren added.
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