Argenx poised to expand Vyvgart market off new phase 3 data

Netherlands-based argenx has published positive topline results from its ADAPT SERON trial of its market-leading drug for generalised myasthenia gravis (gMG) Vyvgart (efgartigimod). Significantly, the results show the drug is effective in AChR-Ab seronegative patients, who make up about 20% of gMG patients and have historically had few to no treatment options.

gMG is a rare but debilitating autoimmune disease that can lead to muscle weakness, breathing troubles, difficulty swallowing, and impaired speech and vision. Despite being a rare disease impacting less than a million people worldwide, gMG treatment is an increasingly crowded market, with argenX recently facing new competition from much larger pharma companies including Johnson & Johnson, AstraZeneca, and UCB.

However, many of those treatments are only effective in the approximately 80% of gMG patients who have detectable antibodies against the acetylcholine receptor (AChR) in their blood. Of the 20% of patients who lack those antibodies, about half have other types of antibodies called anti-MuSK or anti-LRP4 antibodies. Some existing therapies (such as UCB's Rystiggo (rozanolixizumab)) can target anti-MuSK antibodies. The final 10% of gMG patients have no detectable antibodies against AChR, MuSK, or LRP4 and are referred to as triple seronegative. As of now, neither anti-LRP4 Ab positive patients nor triple seronegative patients have any approved treatment options.

ADAPT SERON, a double-blind, multi-centre RCT studying 119 AChR-Ab seronegative patients in China, the Middle East, North America, and Europe, met its primary endpoint, concluding that Vyvgart led to "significant and clinically meaningful improvement in MG-ADL (Myasthenia Gravis Activities of Daily Living) total score compared to placebo" and was well-tolerated and safe. Full detailed results will be shared at an upcoming conference.

“The results of the ADAPT SERON study, the largest study to date of AChR-Ab seronegative gMG, confirm that VYVGART now has the potential to be a targeted, effective, safe, and necessary treatment for patients living with gMG, regardless of autoantibody status,” Dr James F. Howard Jr., Professor of Neurology (Neuromuscular Disease) at The University of North Carolina at Chapel Hill School of Medicine and principal investigator for the trial, said in a statement. “Paired with our existing knowledge, these data demonstrate that pathogenic IgGs are underlying drivers of gMG across patient subtypes. This is a critical advancement in the management of this debilitating and unpredictable disease for patients with limited treatment options.”

argenx plans to submit a supplemental biologics license application to the FDA based on this data by the end of the year, which could see Vyvgart approved for these additional patients by 2026 or 2027.