argenx SE a global immunology company focused on transforming outcomes for patients with severe autoimmune diseases, has announced a significant regulatory milestone for its flagship therapy, VYVGART® (IV: efgartigimod alfa-fcab). The U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for the treatment of adults with acetylcholine receptor antibody (AChR-Ab) seronegative generalized myasthenia gravis (gMG) and granted the application Priority Review status. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 10, 2026.
Addressing a Critical Unmet Need in gMG
Generalized myasthenia gravis is a rare, chronic, and often debilitating autoimmune neuromuscular disease characterized by fluctuating muscle weakness and fatigue. While significant progress has been made in the treatment of patients who test positive for AChR antibodies, those who are seronegative continue to face limited and less targeted therapeutic options. The FDA’s decision to grant Priority Review underscores the seriousness of this unmet need and the potential for VYVGART to offer meaningful clinical benefit to a broader population of patients living with gMG.
“Patients living with seronegative gMG continue to face limited treatment options, and there remains a significant need to meaningfully improve their lives,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx. “The FDA’s acceptance of our sBLA with Priority Review status reflects the potential of VYVGART to address this need. This development brings us closer to expanding the use of VYVGART across a broader spectrum of patients with myasthenia gravis.”
Strong Phase 3 Data Supporting the sBLA
The sBLA submission is supported by data from the Phase 3 ADAPT SERON study, a pivotal clinical trial designed to evaluate the efficacy and safety of VYVGART in adults with AChR-Ab seronegative gMG. Importantly, the study included patients across all three seronegative subtypes: MuSK antibody–positive, LRP4 antibody–positive, and triple seronegative gMG.
ADAPT SERON met its primary endpoint, demonstrating a statistically significant improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared with placebo after four weeks of treatment. The primary analysis yielded a p-value of 0.0068, confirming the robustness of the treatment effect.
In the overall study population, patients treated with VYVGART experienced a clinically meaningful mean improvement of 3.35 points from baseline in the MG-ADL total score at week four. Improvements were not limited to a single treatment cycle; sustained benefits in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were observed across subsequent cycles. Notably, these positive outcomes were consistent across all seronegative subgroups, including MuSK+, LRP4+, and triple seronegative patients.
Favorable Safety and Tolerability Profile
VYVGART was generally well tolerated in the ADAPT SERON study, with a safety profile consistent with that observed in prior studies involving patients with AChR-Ab seropositive gMG and other indications. No new safety concerns were identified during the trial, further supporting the suitability of VYVGART for long-term use in this patient population.
The most commonly reported adverse events were infections, including urinary tract and respiratory tract infections, as well as headache. Infusion-related reactions and hypersensitivity reactions were observed but were consistent with the known safety profile of the therapy.
ADAPT SERON Study Design
The Phase 3 ADAPT SERON study is a randomized, double-blind, placebo-controlled, multicenter trial conducted across North America, Europe, China, and the Middle East. A total of 119 adults with confirmed AChR-Ab seronegative gMG were enrolled.
In Part A of the study, participants were randomized 1:1 to receive four once-weekly intravenous infusions of efgartigimod or placebo, followed by a five-week observation period and primary endpoint analysis. Part B is an open-label extension in which participants receive fixed cycles of efgartigimod infusions, with additional cycles administered based on individual clinical status.
The primary endpoint was the change from baseline in MG-ADL total score at day 29 in Part A. Secondary and exploratory endpoints included assessments using QMG, MG-QoL 15r, Myasthenia Gravis Composite (MGC), and EQ-5D-5L visual analog scale. All participants had a confirmed diagnosis of gMG by an independent expert panel and were receiving stable background therapy prior to enrollment.
Understanding AChR-Ab Seronegative gMG
Approximately 80% of patients with generalized myasthenia gravis have detectable antibodies against the acetylcholine receptor and are classified as AChR-Ab seropositive. The remaining 20% are considered AChR-Ab seronegative and may have antibodies targeting other neuromuscular junction proteins, such as muscle-specific tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4). A subset of patients—known as triple seronegative—do not have detectable antibodies against AChR, MuSK, or LRP4.
These seronegative patients often experience a higher disease burden and have historically been underrepresented or excluded from clinical trials. Currently, there are no approved therapies specifically indicated for patients with anti-LRP4 antibodies or for triple seronegative gMG, highlighting the potential significance of VYVGART’s expanded indication.
About VYVGART
VYVGART is a human IgG1 antibody fragment that targets the neonatal Fc receptor (FcRn), leading to a reduction in circulating pathogenic IgG autoantibodies. It is the first approved FcRn blocker for the treatment of adults with generalized myasthenia gravis who are anti-AChR antibody positive in the United States, European Union, China, and Canada. In Japan, it is approved for adults with gMG who have had an insufficient response to steroids or non-steroidal immunosuppressive therapies.
With the FDA’s Priority Review of the sBLA, argenx moves one step closer to expanding access to VYVGART for patients with seronegative gMG, potentially reshaping the treatment landscape for a population with long-standing unmet medical needs.
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