A myasthenia gravis treatment revolution has taken place in the past four years, spurred by an initial approval for argenx’s first-in-class FcRn blocker Vyvgart at the end of 2021 and buttressed by a series of additional green lights for rival drugmakers in the ensuing years.

Now, in a bid to ensure that the widest swath of people with generalized myasthenia gravis (gMG) can benefit from its blockbuster medicine, argenx is heading to the FDA with positive data in a subset of patients long overlooked in the treatment paradigm.

After reporting a topline win in August, argenx on Wednesday provided a deeper breakdown of the results from its late-stage ADAPT SERON trial, which assessed the company’s flagship FcRn blocker, Vyvgart (efgartigimod), in the subset of generalized myasthenia gravis (gMG) patients who are known as seronegative.

Unlike most gMG patients, people with seronegative disease lack detectable acetylcholine receptor (AChR) or muscle-specific receptor tyrosine kinase (MuSK) antibodies in their blood, which can make the already rare autoimmune condition even trickier to diagnose.

Broadly speaking, myasthenia gravis causes communication between the body’s nerves and muscles to break down. This can lead to difficulty chewing, swallowing, breathing and talking, and can cause muscle weakness, blurred vision and other frequently debilitating symptoms.

To be eligible for the current crop of approved gMG treatments, patients must test positive for either AChR or MuSK antibodies. Argenx aims to change that with its positive readout across all three subtypes of seronegative patients.

Argenx will head to regulators with the data and is aiming for an expansion of Vyvgart into all three seronegative gMG subtypes, classified as MuSK-positive, LRP4-positive and triple seronegative, Luc Truyen, M.D., Ph.D., argenx’s chief medical officer, said in an interview with Fierce Pharma.

The company’s study specifically evaluated Vyvgart’s original, infused formulation, but argenx will seek simultaneous approval for both IV Vyvgart and the drug’s subcutaneous format—known as Hytrulo— in the seronegative population, Truyen explained.

The seronegative readout was among multiple that argenx presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting (AANEM) and the Myasthenia Gravis Foundation of America (MGFA) scientific sessions in San Francisco this week. The company additionally laid out results on Vyvgart in adolescents with gMG, unveiled long-term data out to nearly 170 weeks and presented on the drug’s ability to help patients reduce the use of steroids.

The seronegative data—and the wider body of results across myasthenia gravis populations that argenx is presenting in San Francisco this week—are informed by the “underlying principle” that the company work toward “a state where no MG patient is left behind,” Truyen said.

A seronegative success

Taking a closer look at ADAPT SERON, argenx’s drug enabled the study to meet its primary endpoint by helping patients reach a statistically significant improvement over placebo on the Myasthenia Gravis Activities of Daily Living (MG-ADL) test—a common metric of gMG symptoms.

Specifically, patients treated with Vyvgart charted an average positive change from baseline of 3.35 points on the MG-ADL scale at four weeks, a result associated with “significant improvements” in one or multiple abilities in breathing, eating, eyesight and motor functions, argenx said in an Oct. 29 press release.

By comparison, patients in the trial's placebo cohort charted a 1.9 point average improvement on the MG-ADL metric, argenx noted in a slide deck accompanying its presentation Thursday. 

Further, improvements conferred by Vyvgart across both MG-ADL and the quantitative myasthenia gravis (QMG) score assessment (PDF) appeared “increasingly pronounced across subsequent treatment cycles,” argenx noted. This held true across all three subgroups of seronegative patients, the company added.

Argenx’s drug was well tolerated across the seronegative groups, and no new safety flags were raised in the phase 3 trial, the company pointed out.

ADAPT SERON enrolled 119 patients across the three seronegative gMG subtypes, representing the “largest dedicated study in seronegative patients” to date, Truyen said during his conversation with Fierce.

In an important caveat, Truyen noted that the trial wasn’t statistically powered to examine the drug's performance in each seronegative subtype.

“That wasn’t the intent,” he clarified. “The intent was overall population—MG-ADL significantly better than placebo—and we met that target. Of course, we’ll be digging in and looking at the different subtypes.”

Vyvgart’s strong showing in the gMG patients—regardless of their autoantibody status—further cements the drugmaker’s thesis that pathogenic immunoglobulin G is an “underlying driver” of myasthenia gravis across the subtypes of the rare autoimmune disease, argenx said Wednesday.

Truyen added that he’s felt encouraged that Vyvgart’s effectiveness in gMG is bearing out “across the board.”

Following Vyvgart’s approval in late 2021—which marked argenx’s first—several other novel gMG treatments have entered the fold in the form of Alexion’s Ultomiris, UCB’s Rystiggo and, most recently, Johnson & Johnson’s Imaavy.

J&J’s offering, which belongs to the same FcRN blocker class as Vyvgart, currently boasts an approval in a wider gMG population than its argenx rival, covering patients who are both AChR- or MuSK-antibody positive. By comparison, Vyvgart is only cleared to treat gMG patients who test positive for AChR antibodies.

That said, a green light across the full seronegative patient spectrum would turn things back around in Vyvgart’s favor, analysts at William Blair noted earlier this year. The analysts predicted that a seronegative nod from the FDA could add some 11,000 new patients to Vyvgart’s current U.S. prescribing pool.

Touching on the other presentations on argenx’s agenda this week, Truyen spotlighted the significance of the company’s adolescent data, and how those results will fuel the next phase in Vyvgart’s push to reach even deeper into the gMG population.

In that trial, argenx’s drug helped patients between the ages of 12 and 17 years achieve similar improvements to those seen in adults on the MG-ADL metric and minimal symptom expression, Truyen pointed out.

“With these data in hand, we can now model the dose for even younger kids, and that’s going to be the next chapter,” he explained. Juvenile myasthenia gravis is estimated to account for around 10% to 15% of cases of the disease in Europe and North America. 

Argenx last year reported net product sales of nearly $2.2 billion, thanks to the sustained momentum behind both Vyvgart and Hytrulo. Aside from gMG, Vyvgart also boasts a green light in the rare peripheral nervous system disease chronic inflammatory demyelinating polyneuropathy (CIDP) and carries an approval in primary immune thrombocytopenia (ITP) in Japan.

The company is additionally testing efgartigimod—the generic name for Vyvgart’s active ingredient—in a host of other autoimmune conditions, from ocular myasthenia gravis and thyroid eye disease to myositis, Sjogren’s disease and lupus nephropathy, among other potential indications.