Following a three-month delay, the U.S. FDA approved under priority review a subcutaneous formulation of Argenx NV’s efgartigimod, offering patients a much more convenient way to treat generalized myasthenia gravis (gMG).
The decision came on the company’s PDUFA date, June 20. Branded Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc), the drug reduces IgG antibodies and blocks their recycling process by targeting FcRn.
Amsterdam-based Argenx is the first company to gain approval of an injectable treatment for gMG. The intravenous version, Vyvgart (efgartigimod alfa-fcab), was approved by the FDA in December 2021, becoming the first FcRn antagonist cleared for gMG. It was also approved later in the European Union, Japan and the U.K., and it generated $401 million in global net product sales in 2022.
The product in the intravenous (I.V.) form is administered at 10 mg/kg through a one-hour fusion once a week for four weeks, with subsequent treatment determined by a clinical evaluation. The new subcutaneous (SC) version, however, offers “a convenient one-minute injection,” said analyst Douglas Tsao, of H.C. Wainwright & Co., offering an “additional competitive advantage.”
In November 2022, the U.S. FDA accepted for priority review the BLA for SC efgartigimod (1,000 mg), which is formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme Therapeutics Inc.’s Enhanze drug delivery technology. The original PDUFA date was March 20, but the review was pushed back by the agency in January following information submitted by Argenx, which constituted a major amendment.
Efgartigimod is differentiated from competitors as the “FcRn blockade inhibits all mechanisms associated with the pathogenicity of autoantibodies,” Tsao said, adding that “within the FcRn space, Argenx has the largest dataset” and a “very consistent safety profile in the real-world population.”
Another potential player in the gMG space is Brussels-based UCB SA, which gained in January a priority review for its FcRn inhibitor, rozanolixizumab, to treat gMG. An estimated PDUFA date for the infused therapy based on a six-month review timeframe is July 6.
The BLA filing for Vyvgart Hytrulo was based on the phase III Adapt-SC study showing noninferiority to I.V.-administered Vyvgart in adults with gMG. Most patients enrolled were positive for AChR antibodies. The trial met the primary endpoint of total IgG reduction from baseline at day 29 (66.4% Vyvgart Hytrulo vs. 62.2% Vyvgart; p<0.0001). The results were consistent among those with and without AChR antibodies.
The Vyvgart Hytrulo label reads that there is an increased risk of infection, most commonly urinary tract and respiratory tract infections, and that more patients on the drug had below normal levels for white blood cell counts, lymphocyte counts and neutrophil counts.
Argenx’s stock (NASDAQ:ARGX) closed at $337.51 on Dec. 20, 2021, following the first approval for the I.V. version. It was trading at $396.26 early on June 21, following approval of the SC version.