Under-the-skin efgartigimod wins approval in UK for gMG adults

An under-the-skin, or subcutaneous, injectable formulation of efgartigimod alfa has been approved in the U.K. as an add-on therapy for adults with generalized myasthenia gravis (gMG) who test positive for antibodies against the acetylcholine receptor (AChR).

This new formulation will be marketed in the U.K. as Subcutaneous Vyvgart. In the European Union, where the therapy was approved late last year, it’s sold under a variation of that name, as Vyvgart SC. Meanwhile, it’s known in the U.S. — where it won its first approval in June 2023 — with the brand name Vyvgart Hytrulo, and also is approved in Japan as Vyvdura.

An into-the-vein, or intravenous, formulation of efgartigimod, sold as Vyvgart, won approval in the U.K. last year.

Argenx, the therapy’s developer, will now work with U.K. authorities to make the subcutaneous version available to patients, with the possibility of self-administration.

“Today’s authorisation marks another important step forward for the management of gMG in the UK, offering a simpler way to administer efgartigimod, through a subcutaneous injection,” David Knechtel, general manager of Argenx UK, said in a company press release. “Our focus now will be on ensuring seamless access to this medicine for all those who could potentially benefit, and we are working closely with authorities across the U.K. to make this a reality.”

Therapy approved for patients with anti-AChR-positive gMG

In MG, self-reactive antibodies interfere with the communication between nerve and muscle cells. Most commonly, these antibodies target AChR, a protein receptor found on the surface of muscle cells. Although a number of different treatment approaches are available to manage myasthenia gravis, many patients with gMG continue to experience symptoms of the autoimmune disorder.

“There is a clear unmet need for an effective therapy that can be used to manage gMG patients whose symptoms remain significantly uncontrolled despite established clinical management,” said Sivakumar Sathasivam, PhD, consultant neurologist and MG lead at the Walton Centre, in Liverpool.

Subcutaneous efgartigimod provides a new and easier-to-administer treatment option for these people, with the ability to potentially impact their quality of life and disease burden.

Efgartigimod, the active ingredient in Vyvgart and Subcutaneous Vyvgart, is designed to block the neonatal Fc receptor (FcRn), a protein that normally helps prevent antibodies circulating in the bloodstream from being degraded. Such a blockade is expected to stimulate antibody degradation and lower the levels of MG-causing antibodies, thereby easing disease symptoms.

“Subcutaneous efgartigimod provides a new and easier-to-administer treatment option for these people, with the ability to potentially impact their quality of life and disease burden,” Sathasivam said.

Intravenous Vyvgart was approved in the U.K. in March 2023, based on data from the Phase 3 ADAPT trial (NCT03669588), which had enrolled 167 gMG patients. Its results showed that more than twice as many participants responded to the therapy versus a placebo (67.7% vs. 29.7%), with a meaningful easing of symptoms.

The Phase 3 ADAPT-SC trial (NCT04735432) then provided data to support the U.K. approval of the subcutaneous formulation, directly comparing it to intravenous Vyvgart in 110 gMG adults.

Trial data showed that subcutaneous efgartigimod reduced the levels of anti-AChR antibodies to a degree similar to that seen with the intravenous version. Its ability to provide clinically meaningful benefits across multiple assessments of symptoms and disease severity also was similar. Both formulations also had an identical safety profile.

“Argenx is continually looking at how we can help improve the care of people living with gMG and our hope is that this may provide greater flexibility and choice to physicians, and their patients,” Knechtel said.