FDA Approves Vyvgart Hytrulo to Treat Patients with Anti-AChR Antibody-Positive Generalized Myasthenia Gravis

The Food and Drug Administration (FDA) approved Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc; Argenx SE, Amsterdam, Netherlands), a drug that is injected subcutaneously to treat generalized myasthenia gravis (gMG) in adult patients who test positive for anti-acetylcholine receptor (AChR) antibodies. The FDA approval was based upon results from the phase 3 ADAPT-SC clinical trial (NCT04735432), which demonstrated Vyvgart Hytrulo’s efficacy in reducing anti-AChR antibody concentrations with noninferiority (P<.0001) compared to intravenous Vyvgart (efgartigimod alfa-fcab, Argenx SE, Amsterdam, Netherlands). Both Vyvgart Hytrulo and Vyvgart were designed to bind to the neonatal Fc receptor (FcRn) to reduce circulation of human immunoglobulin G (IgG) in the blood. Anti-AChR antibodies, present in around 85% of the patient population, are a type of IgG that disrupt AChR, causing muscle weakness.

ADAPT-SC was a randomized, open-label, parallel-group, multicenter bridging study following the phase 3 ADAPT clinical trial (NCT03669588). ADAPT established the efficacy, safety, and tolerability of intravenously injected Vyvgart in treating gMG in 167 participants, resulting in its FDA approval in December of 2021. In ADAPT-SC, 110 adult participants with gMG were randomly assigned 1:1 to receive multiple injections of either subcutaneous Vyvgart Hytrulo or intravenous Vyvgart. Patients were included if they scored at least a 5 at screening and baseline on the Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale, with at least 50% of total score attributable to non-ocular symptoms.

Results from the phase 3 ADAPT-SC trial include:

• Mean total IgG reduction of 66.4% from baseline at day 29 in participants treated with Vyvgart Hytrulo, compared to a 62.2% reduction for intravenous Vyvgart 
• 69.1% of participants treated with Vyvgart Hytrulo had at least a 2-point improvement in MG-ADL Scale score for at least 4 consecutive weeks
• 65.5% of patients treated with Vyvgart Hytrulo had at least a 3-point improvement on the Quantitative Myasthenia Gravis (QMG) score for at least 4 consecutive weeks.
• Minimal symptom expression (MSE) was achieved in 37% of participants treated with Vyvgart Hytrulo after 1 treatment cycle
• Results were consistent across individuals with and without anti-AChR antibodies

“The clinical trials of VYVGART continue to show significant benefit to patients with a favorable safety profile and clear improvements in gMG disease scores,” said James F. Howard Jr, MD, ADAPT-SC Principal Investigator.

Vyvgart Hytrulo is devised with recombinant human hyaluronidase PH20 (rHuPH20) drug delivery technology. Vyvgart is thought to improve gMG through inhibition of IgG recycling, which results in more lysosomal destruction of IgG and overall lower levels of the antibody.