Zai Lab partner argenx announced that the U.S. Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) for efgartigimod subcutaneous injection (1000mg efgartigimod-PH20) in adults with generalized myasthenia gravis (gMG).

Efgartigimod subcutaneously is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) using Halozyme's ENHANZE® drug delivery technology. ENHANZE technology facilitates subcutaneous administration of biologics typically administered by intravenous infusion.

The Biologics License Application includes data from the Phase 3 clinical study ADAPT-SC, which evaluated the pharmacodynamic non-inferiority of efgartigimod subcutaneously versus VYVGART intravenous infusion in adult patients with gMG. Most enrolled patients were positive for acetylcholine receptor (AChR) antibodies, but patients with no detectable AChR antibodies were also included in this clinical study.

The ADAPT-SC study met its primary endpoint (p<0.0001), demonstrating non-inferiority of subcutaneous efgartigimod for reduction in total immunoglobulin G (IgG) at day 29 compared with VYVGART intravenous infusion. Subcutaneous injections of efgartigimod demonstrated a mean reduction of 66.4% in total IgG at day 29 compared to baseline levels, compared with 62.2% for VYVGART. The findings were consistent across the overall population, including patients with AChR antibodies and those with no detectable AChR antibodies.

In addition, 69.1% of patients treated with efgartigimod subcutaneously achieved a Myasthenia Gravis Activities of Daily Living (MG-ADL) score response. Responders were defined as at least a 2-point improvement on the MG-ADL score for at least 4 weeks. Quantitative myasthenia gravis (QMG) score responses were achieved in 65.5% of patients treated with efgartigimod subcutaneously. Responders were defined as at least a 3-point improvement in the QMG score within the first treatment cycle and a duration of at least 4 weeks. After one treatment cycle, 37% of patients treated with efgartigimod subcutaneously achieved minimal symptom expression (MSE), a measure of asymptomatic status. The onset of action was also consistent with the Phase 3 ADAPT study.

Efgartigimod subcutaneous injection therapy demonstrated a safety profile consistent with the Phase 3 clinical study ADAPT. Patients were generally well tolerated; the most common adverse event was injection site reactions (ISRs), which are usually observed with subcutaneous biologics. All ISRs were mild to moderate and disappeared over time. Upon completion of the ADAPT-SC study, 95% of patients will enter the ADAPT-SC+ study, a three-year open-label extension study to evaluate the long-term safety and tolerability of efgartigimod subcutaneously.