FDA Approves Subcutaneous Vyvgart for Myasthenia Gravis

The FDA has approved Argenx’s Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) to treat patients with generalized myasthenia gravis (gMG). It is indicated for adult patients who are anti-acetylcholine receptor (AChR) antibody positive, which represents about 85% of the total generalized myasthenia gravis population.

Generalized myasthenia gravis is a rare autoimmune disease that leads to weakness in skeletal muscles, causing muscles to tire and weaken. It occurs when the immune system makes immunoglobulin G IgG1) antibodies that destroy the ACh receptor. It is estimated that there are two to seven people in every 10,000 that have myasthenia gravis, according to the Muscular Dystrophy Association.

Vyvgart intravenous was approved in December 2021, and it binds to the neonatal Fc receptor (FcRn) to reduce circulating IgG. Vyvgart Hytrulo, a subcutaneous (under the skin) therapy, adds the recombinant human hyaluronidase PH20 to efgartigimod alfa. It uses Halozyme’s ENHANZE drug delivery technology to facilitate subcutaneous delivery. The addition of human hyaluronidase PH20 using ENHANZE means the therapy can be delivered in about 30 to 90 seconds compared with the intravenous therapy, which takes about an hour. It is delivered in cycles of once weekly injections for four weeks. Vyvgart Hytrulo is the first approved FcRn blocker administered by subcutaneous injection. It is expected to be available in July 2023.

The typical net price for Vyvgart is about $225,000 annually, and Argenx indicates Vyvgart Hytrulo will be priced at parity. The company provides copay assistance with a maximum of $25,000 a year.

Allison Foss

“The availability of another gMG treatment option from argenx, now in a subcutaneous delivery, is a meaningful advancement for the patient community. Patients now have the opportunity to receive treatment in an infusion center, at home or at a physician’s office - providing more flexibility and freedom of choice that can make daily living easier for gMG patients and their caregivers,” Allison Foss, executive director of the Myasthenia Gravis Association, said in a press release.

The approval of the Vyvgart Hytrulo was based on positive results from the phase 3 ADAPT-SC study, which demonstrated a reduction in anti-AChR antibody levels comparable with intravenous Vyvgart in adult gMG patients. ADAPT-SC was a bridging study to the phase 3 ADAPT study, which formed the basis for approval of intravenous Vyvgart in December 2021.

In the ADAPT-SC study, the primary endpoint of noninferiority was met and Vyvgart Hytrulo demonstrated mean total IgG reduction of 66.4% from baseline at day 29, compared with 62.2% with Vyvgart. Additional key secondary endpoints were met, which were consistent with efficacy measures from the ADAPT study identifying the correlation between total IgG reduction and clinical benefit in gMG.

Vyvgart Hytrulo’s safety was consistent with the ADAPT clinical trial with the exception of injection site reactions, which were higher with Vyvgart Hytrulo. It was generally well-tolerated with injection site reactions being the most frequent adverse events.