麻豆传媒

SAVANNAH, Ga. -- Investigational nipocalimab lessened disease severity in generalized myasthenia gravis (gMG), the phase III Vivacity-MG3 trial showed.

The primary endpoint was the change in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores from baseline to the average over weeks 22, 23, and 24 in seropositive patients with gMG. The MG-ADL scale ranges from 0 to 24, with higher scores indicating more severe symptoms.

Nipocalimab plus standard of care showed a greater improvement in MG-ADL scores (-4.7 points) compared with placebo plus standard of care (-3.25 points), a difference of -1.45 points (SE 0.470, P=0.002), said Tuan Vu, MD, of the University of South Florida in Tampa.

The study also met key secondary endpoints, Vu noted. The findings were presented at the Myasthenia Gravis Foundation of America (MGFA) session of the American Association of Neuromuscular and Electrodiagnostic Medicine annual meeting.

Nipocalimab is designed to block the immunoglobulin G (IgG) binding site on the neonatal Fc receptor (FcRn) to reduce serum levels of total IgG, including pathogenic IgG autoantibodies in gMG.

"Vivacity is the first registrational study of an FcRn blocker to show sustained efficacy through 6 months fixed-schedule dosing," Vu said,

The pivotal trial included people diagnosed with IIa-IVb gMG who had an MG-ADL score of 6 or higher at baseline. The primary efficacy set included 153 gMG patients who were antibody positive for acetylcholine receptor (AChR+), muscle-specific kinase (MuSK+), or low-density lipoprotein receptor 4 (LRP4+).

At screening, participants had a suboptimal response to stable gMG therapy or had stopped taking corticosteroids or immunosuppressants 4 or more weeks earlier due to intolerance or lack of efficacy.

About half of the primary efficacy set (77 participants) received a nipocalimab 30 mg/kg loading dose and 15 mg/kg once every 2 weeks, plus standard care. The other 76 participants received placebo plus standard care.

Mean baseline age was about 52, and 60% of participants were women. Mean baseline MG-ADL scores were 9.2 points and mean duration of gMG was 7.9 years. Most participants (87.6%) were anti-AChR+, 10.5% were anti-MuSK+, and 2.0% were anti-LRP4+.

A key secondary endpoint was the change in Quantitative Myasthenia Gravis (QMG) scores from baseline to the average over weeks 22, 23, and 24. The QMG assesses gross motor and other functions; scores range from 0 to 39, with higher scores indicating more severe MG.

At baseline, mean QMG scores were 15.4. Participants in the nipocalimab plus standard care group showed a greater improvement (-4.86 points) compared with placebo (-2.05 points), for a difference of -2.81 points (SE 0.710, P<0.001).

The responder rate, measured as MG-ADL improvements of 2 points or more from baseline, also was greater in the nipocalimab group than in the placebo group (68.8% vs 52.6%, P=0.021) from weeks 22 to 24.

A total of 196 gMG patients were included in the safety analysis; of these 42 were seronegative and not part of the primary efficacy analysis.

"The drug was pretty well tolerated," Vu said. The most common adverse events with nipocalimab treatment were headache (14.3%), muscle spasms (12.2%), myasthenia gravis worsening (12.2% in both the nipocalimab and placebo groups), COVID-19 (15.3%), and peripheral edema (11.2%).

One person died in the nipocalimab group, and two died in the placebo group. The deaths in both arms were assessed as not being related to treatment.

In August, Johnson & Johnson to the FDA seeking approval of nipocalimab to treat gMG. Nipocalimab also is being studied in other rare diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP).

In the past 7 years, five new drugs have been approved by the FDA to treat myasthenia gravis -- eculizumab (Soliris), rozanolixizumab (Rystiggo), ravulizumab (Ultomiris), zilucoplan (Zilbrysq), and efgartigimod (Vyvgart), which also targets FcRn and is approved for CIDP.

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