On 20 April, at the 2026 American Academy of Neurology (AAN) meeting, Argenx announced positive results from the Phase III, double-blind, placebo-controlled, ADAPT SERON study of Vyvgart (efgartigimod alfa) (NCT06298552). The study sought to evaluate the efficacy and safety of efgartigimod alfa in adult participants with acetylcholine receptor binding antibody seronegative (AChR-) generalised myasthenia gravis (gMG). The study met its primary endpoint (p = 0.0068), demonstrating that AChR- gMG patients treated with Vyvgart achieved a statistically significant and clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared to placebo.
Vyvgart is a prescription medicine used to treat gMG in adults who are AChR+. It is designed to bind with high affinity to block the neonatal Fc receptor (FcRn) and reduce levels of circulating immunoglobulin G (IgG) antibodies, potentially without impact on other immune functions. The Phase III ADAPT SERON study was a randomised, double-blind, placebo-controlled study evaluating the safety and efficacy of efgartigimod in adults with AChR-Ab seronegative gMG (n=119) across North America, Europe, China, and the Middle East. Part A randomised participants (1:1) to receive four once-weekly infusions of intravenous efgartigimod or placebo, followed by a five-week follow-up and primary analysis. Part B was an open-label extension: participants received two fixed cycles of four once-weekly efgartigimod infusions (four-week interval between cycles); from cycle 3 onward, additional cycles could be started one week or more after the last administration of the previous cycle, based on clinical status. The primary endpoint was the MG-ADL total score change from baseline to Day 29 in part A. Enrolled participants had a confirmed MG diagnosis by an independent panel of experts and an MG-ADL total score of 5 or greater. Participants were eligible to enrol in ADAPT SERON if they were AChR-, which included participants who were muscle-specific tyrosine kinase (Musk) seropositive, low-density lipoprotein receptor-related protein 4 (LRP4) seropositive, or triple seronegative.
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The trial met its primary endpoint, in that efgartigimod demonstrated a significant improvement in the MG-ADL score at Week 4 compared with placebo. The efgartigimod group saw a mean reduction of 3.35 at the end of the four weeks, whereas the placebo group experienced a mean reduction of 1.90. Furthermore, this improvement in MG-ADL score was enhanced across subsequent cycles in the study population during part B of the study, with the benefits remaining consistent amongst all three patient populations involved in the study (Musk+, LRP4+, and triple seronegative). Efgartigimod was also shown to be well-tolerated and demonstrated a safety profile that was consistent with previous clinical trials.
The results of the trial are exciting. Around 80% of patients living with gMG are AChR+, and most of the marketed therapies are indicated for this patient population. However, the remaining 20% do not have detectable serum antibodies directed against AChR. These patients may have detectable autoantibodies targeting other neuromuscular junction proteins such as Musk and LRP4. Anti-Musk antibodies are detected in approximately 1%–10% of patients with gMG, while anti-LRP4 antibodies are detected in approximately 1%–5% of patients with gMG. About 10% of patients do not have any detectable autoantibodies against AChR, Musk, or LRP4, and are referred to as triple seronegative. These triple seronegative patients have historically been excluded from studies and have a higher unmet medical need compared to patients with detectable antibodies.
Key opinion leaders (KOLs) previously interviewed by GlobalData have noted that there is a significant unmet need for effective treatments for patients who are Musk+, LRP4+, or triple seronegative. There are fewer effective treatments available for AChR- gMG patients in general, but for LRP4+ patients and triple seronegative patients, there are no approved treatments available at all. The positive data from the ADAPT SERON trial could therefore pave the way for a shift in the treatment paradigm, marking the arrival of a new treatment option for a historically marginalised patient population. Moreover, should Vyvgart’s label be expanded, it could be the first disease-modifying therapy (DMT) to receive approval across all MG serologies. Vyvgart is already well-respected and a market leader amongst DMTs; it is also familiar to clinicians, with a well-understood safety profile, so it may see fast uptake amongst AChR- patients.
The findings from the ADAPT SERON trial underscore the role of Vyvgart as a transformative treatment for gMG. By demonstrating sustained improvements in MG-ADL, alongside reductions in IgG levels, Vyvgart shows that it can address critical unmet needs for AChR- patients. Its steroid-sparing effect further enhances its appeal, offering a pathway to improved quality of life by reducing reliance on corticosteroids and their associated side effects. With a consistent safety profile and promising long-term efficacy, efgartigimod represents a promising advancement in gMG therapy, paving the way for broader disease management and better patient outcomes.
