argenx SE a global immunology company focused on developing innovative therapies for patients with severe autoimmune diseases, announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review a supplemental Biologics License Application (sBLA) for VYVGART® (intravenous efgartigimod alfa-fcab). The application seeks approval of VYVGART for the treatment of adults with acetylcholine receptor antibody (AChR-Ab) seronegative generalized myasthenia gravis (gMG), a patient population with substantial unmet medical need. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 10, 2026.
Priority Review designation is granted to therapies that, if approved, have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The FDA’s decision underscores the clinical relevance of the data supporting VYVGART and highlights the urgent need for effective therapies for patients living with seronegative gMG, who historically have had limited approved treatment options.
“Patients living with seronegative gMG continue to face limited treatment options, and there remains a significant need to meaningfully improve their quality of life,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx. “The FDA’s acceptance of our sBLA with Priority Review reflects the potential of VYVGART to address this unmet need. This milestone brings us closer to expanding the use of VYVGART to a broader spectrum of patients with myasthenia gravis, and we look forward to continuing our constructive dialogue with the FDA during the review process.”
The sBLA is supported by results from the Phase 3 ADAPT SERON study, a global, randomized, double-blind, placebo-controlled 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 major seronegative subtypes: muscle-specific tyrosine kinase antibody–positive (MuSK+), low-density lipoprotein receptor–related protein 4 antibody–positive (LRP4+), and triple seronegative gMG.
The ADAPT SERON trial 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 endpoint analysis yielded a p-value of 0.0068, confirming the robustness of the treatment effect. MG-ADL is a validated, patient-reported outcome measure that assesses the functional impact of myasthenia gravis symptoms on everyday activities, including speaking, chewing, swallowing, breathing, and limb strength.
In the overall study population, patients treated with VYVGART experienced a mean improvement of 3.35 points from baseline in the MG-ADL total score at week four, a change considered clinically meaningful. Improvements were not limited to the initial treatment cycle. Sustained and consistent benefits were observed across subsequent treatment cycles in both MG-ADL and Quantitative Myasthenia Gravis (QMG) scores. These benefits were seen across all evaluated subgroups, including MuSK+, LRP4+, and triple seronegative patients, supporting the broad applicability of VYVGART in seronegative gMG.
VYVGART was generally well tolerated in the ADAPT SERON study. The safety profile observed in seronegative gMG patients was consistent with the established safety profile of VYVGART in patients with AChR-Ab seropositive gMG and in other approved indications. No new safety signals or unexpected adverse events were identified, reinforcing confidence in the therapy’s risk–benefit profile.
The Phase 3 ADAPT SERON study enrolled 119 adults with confirmed AChR-Ab seronegative gMG across multiple regions, including North America, Europe, China, and the Middle East. In Part A of the study, participants were randomized in a 1:1 ratio to receive four once-weekly intravenous infusions of efgartigimod or placebo, followed by a five-week follow-up period during which the primary efficacy analysis was conducted. Part B of the study is an open-label extension in which participants receive two fixed cycles of four once-weekly infusions, with a four-week interval between cycles. From the third cycle onward, additional treatment cycles may be initiated at least one week after the last administration of the prior cycle, based on individual clinical status.
Eligible participants had a confirmed diagnosis of myasthenia gravis established by an independent panel of experts and an MG-ADL total score of at least five at baseline. Patients were required to be on a stable dose of at least one standard gMG therapy prior to randomization, including acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressive agents. Patients qualified as AChR-Ab seronegative if they were MuSK-Ab positive, LRP4-Ab positive, or negative for AChR, MuSK, and LRP4 antibodies.
Generalized myasthenia gravis is a rare, chronic autoimmune neuromuscular disease characterized by fluctuating and often debilitating muscle weakness and fatigue. The disease is caused by pathogenic immunoglobulin G (IgG) antibodies that disrupt neuromuscular transmission at the neuromuscular junction. While approximately 80% of patients with gMG are AChR-Ab seropositive, around 20% are AChR-Ab seronegative. This latter group includes patients with antibodies against MuSK or LRP4, as well as triple seronegative patients who lack detectable antibodies against all three known targets.
Seronegative gMG patients, particularly those who are LRP4-positive or triple seronegative, have historically been underrepresented in clinical trials and face a higher disease burden with fewer approved treatment options. Currently, there are no approved therapies specifically indicated for patients with anti-LRP4 antibodies or for triple seronegative gMG, underscoring the significance of the FDA’s Priority Review of VYVGART for this population.
If approved, VYVGART has the potential to become an important new treatment option for adults with AChR-Ab seronegative gMG, offering hope to patients who have long faced limited therapeutic choices and persistent disease-related challenges.
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