argenx SE, a global immunology company, announced positive topline results from the pivotal ADAPT SERON study of Vyvgart (efgartigimod alfa-fcab, IV).
The phase 3 trial met its primary endpoint (p=0.0068). Patients with acetylcholine receptor antibody–negative (AChR-Ab seronegative) generalized myasthenia gravis (gMG) showed statistically significant and clinically meaningful improvement in MG-ADL total score versus placebo.
Regulatory Pathway Ahead
Based on these findings, argenx plans to file a supplemental Biologics License Application (sBLA) with the FDA.
- Goal: expand Vyvgart’s label to adult AChR-Ab seronegative gMG patients across all three subtypes—MuSK+, LRP4+, and triple seronegative.
- Detailed trial data will be shared at an upcoming medical meeting.
Safety Profile
Vyvgart was well tolerated across AChR-Ab seronegative subtypes.
- Safety results were consistent with previous studies in AChR-Ab seropositive gMG and other indications.
- No new safety concerns were reported.
Expert Commentary
“The ADAPT SERON study, the largest in AChR-Ab seronegative gMG, confirms Vyvgart’s potential as a targeted, safe, and effective therapy,”
- Dr. James F. Howard Jr., principal investigator, University of North Carolina.
“These data show pathogenic IgGs drive gMG across patient subtypes. This is a critical step for patients with limited treatment options,” he added.
argenx CMO Dr. Luc Truyen noted: “This study underscores our commitment to the MG community. We aim to reach all patients living with this debilitating condition.”
Study Design
- Type: Randomized, double-blind, placebo-controlled, multi-center.
- Participants: 119 adults with confirmed seronegative gMG, across North America, Europe, China, and the Middle East.
- Part A: Patients received 4 once-weekly infusions of Vyvgart or placebo, followed by a 5-week follow-up.
- Part B: Open-label extension. Patients received 2 fixed treatment cycles, then additional cycles as needed.
- Primary Endpoint: MG-ADL total score change from baseline to day 29.
Participants were required to have:
- MG-ADL score ≥5 at baseline.
- A confirmed gMG diagnosis by an independent panel.
- Stable dosing of at least one gMG therapy, including acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressants.
Disease Context
gMG is a rare autoimmune neuromuscular disease. Pathogenic IgGs disrupt neuromuscular transmission, leading to muscle weakness and fatigue.
- 80% of patients are AChR-Ab seropositive.
- ~20% are seronegative, including:
- MuSK-Ab positive (1–10%).
- LRP4-Ab positive (1–5%).
- Triple seronegative (~10%), historically excluded from trials and facing higher disease burden. - Currently, no approved therapies exist for LRP4+ or triple seronegative patients.
About Vyvgart
Vyvgart is a human IgG1 antibody fragment that binds the neonatal Fc receptor (FcRn), lowering circulating IgG autoantibodies.
- First approved FcRn blocker in the US, EU, China, and Canada for AChR-Ab positive gMG.
- Approved in Japan for adults with gMG unresponsive to steroids or immunosuppressants.
About argenx
argenx is a global immunology company developing antibody-based medicines for severe autoimmune diseases. Its Immunology Innovation Program (IIP) connects academic research with drug development to build a world-class portfolio.
