European panel recommends under-the-skin efgartigimod for gMG
The CHMP's opinion now goes to the European Commission for final decision
A European Medicines Agency (EMA) committee has recommended the approval of Argenx’s under-the-skin, or subcutaneous, formulation of efgartigimod as an add-on to standard therapy for adults with generalized myasthenia gravis (gMG) who have antibodies against acetylcholine receptors (AChRs).
Argenx’s into-the-vein (intravenous) formulation of efgartigimod, sold as Vyvgart, is already approved for this patient population in the European Union, and also is cleared in a number of other countries.
The subcutaneous version was approved in the U.S. for adults with gMG who are positive for anti-AChR antibodies earlier this year, where it is marketed as Vyvgart Hytrulo.
The opinion of the EMA committee, called the Committee for Medicinal Products for Human Use (CHMP), will be considered by the European Commission (EC) when making its final decision, which is expected within the next 60 days. While that decision does not necessarily align with the CHMP opinion, it often does. The EC’s final decision will apply to all 27 European Union member states, as well as Iceland, Norway, and Liechtenstein.
“The positive recommendation by the CHMP for the [subcutaneous] injectable formulation of efgartigimod brings us one step closer to broadening our treatment offering for people living with gMG in Europe,” Anant Murthy, PhD, Argenx’s general manager in Europe, the Middle East, and Africa, said in a company press release.
“Our mission is to transform the treatment of severe autoimmune disease, and we remain committed to providing gMG patients a second innovation that could further address treatment burden,” Murthy said.
How efgartigimod works
Efgartigimod, the active ingredient in Vyvgart and Vyvgart Hytrulo, works to block a protein called the neonatal Fc receptor (FcRn). This protein normally works to stabilize certain antibodies called immunoglobulin G (IgG) in the bloodstream. The self-reactive antibodies implicated in gMG, including those targeting AChRs, belong to this antibody family. By blocking FcRn, efgartigimod is expected to accelerate the breakdown of the harmful antibodies that drive gMG symptoms.
The subcutaneous version is formulated with a drug delivery technology from Halozyme, called ENHANZE, that helps facilitate subcutaneous delivery of medications originally designed to be given through intravenous infusions.
Both formulations initially are delivered once weekly over a four-week treatment cycle, with additional cycles given based on a patient’s clinical response.
Still, the subcutaneous version is thought to offer greater convenience relative to the intravenous formulation. While intravenous infusions take about an hour, subcutaneous injections take about 30 to 90 seconds, or less than two minutes total, to be administered.
Subcutaneous delivery may provide flexibility
While both are currently administered by a healthcare provider, subcutaneous delivery may offer the potential for self-administration in the future.
“We are particularly pleased with the possibility for self-administration of the [subcutaneous] formulation, which may provide additional treatment flexibility for physicians and patients,” Murthy said.
The safety and efficacy of the new formulation was demonstrated in the Phase 3 ADAPT-SC study (NCT04735432), which was completed in 2021. A total of 110 adults with gMG were assigned randomly to receive either four weekly doses of subcutaneous efgartigimod (1,000 mg) or Vyvgart (10 mg/kg).
Results showed that the two therapies were similar in their ability to lower IgG levels, and specifically, anti-AChR antibodies. Subcutaneous efgartigimod was associated with a 66.4% reduction in total IgGs, while treatment with Vyvgart led to a 62.2% reduction.
The subcutaneous formulation also led to reductions in symptom severity and life quality gains that were consistent with those seen in the Phase 3 ADAPT trial (NCT03669588) of Vyvgart.
Safety findings were similar to those observed with Vyvgart. However, the subcutaneous medication was associated with more injection-site reactions. While this is typical of subcutaneous biological therapies, these reactions were mild or moderate and did not lead to treatment discontinuations.
Open-label extension study
An ongoing open-label extension study called ADAPT-SC+ (NCT04818671) is investigating the long-term safety and tolerability of subcutaneous efgartigimod for up to 3.5 years.
“I’m pleased to learn of the CHMP’s positive opinion as it represents a significant advancement for the gMG community who would benefit from an additional, effective treatment option that can improve quality of life and better manage this chronic condition,” said Jan De Bleecker, MD, PhD, of Ghent University Hospital and Ghent University, in Belgium.
“In particular, [subcutaneous] efgartigimod has the potential to have a positive impact on treatment convenience, leading to a broader positive impact for patients and healthcare systems,” Bleecker said.