MGFA Session 2026: Treatment cuts gMG hospitalization rates
Clinical trial shows cemdisiran reduces number of myasthenic crises
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- The experimental therapy cemdisiran significantly cuts hospitalization rates for gMG patients, clinical trial data showed.
- It also reduced the number of myasthenic crises and rescue therapy requirements.
- The treatment is under review for approval in the U.S. and EU
Regeneron Pharmaceuticals’ investigational therapy cemdisiran significantly reduced hospitalization rates among people with generalized myasthenia gravis (gMG) in a global clinical trial.
The data from the Phase 3 NIMBLE study (NCT05070858) were presented by trial investigator Ali Habib, MD, a neurologist at the University of California, Irvine, at the Myasthenia Gravis Foundation of America (MGFA) scientific session during the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. Habib’s talk was titled, “Comparison of cemdisiran vs placebo on hospitalization rate in the phase 3 double-blind NIMBLE trial.”
“For people living with generalized myasthenia gravis, every hospitalization avoided is a life less disrupted,” Habib said in an email to Myasthenia Gravis News. “This is why these latest NIMBLE trial results are particularly noteworthy.”
“Fewer emergency interventions and fewer setbacks means more disease control, and treatment with cemdisiran was generally well tolerated,” Habib said.
Approval applications under review
Earlier data from NIMBLE, which showed that the treatment eased overall gMG severity, supported applications to regulators in the U.S. and the European Union seeking approval of the therapy for adults with gMG who have disease-causing antibodies targeting the acetylcholine receptor (AChR) protein.
Both applications are under review; a decision is due in the U.S. in November and in Europe by the second half of 2027. A similar application is expected to be filed with Japanese authorities next year.
gMG is caused when self-reactive antibodies lead to the destruction of AChRs or other proteins needed for nerve-muscle communication, contributing to muscle weakness and fatigue, which are MG symptoms. When these abnormal antibodies bind to certain targets, particularly AChRs and lipoprotein receptor-related protein 4 (LRP4), they activate a part of the immune system, called the complement cascade, which contributes to gMG-related damage. AChR is the most common target of gMG-driving antibodies, while LRP4 is a rarer target.
Cemdisiran uses a technology called small interfering RNA to reduce the production of the C5 complement protein, which in turn prevents activation of the complement cascade. This is expected to control the harmful immune responses driven by antibodies against AChR and LRP4.
The therapy is designed to be given via subcutaneous (under-the-skin) injection once every three months, potentially offering a more convenient alternative to therapies that are taken more frequently.
NIMBLE was designed to evaluate the safety and efficacy of cemdisiran in people with gMG, either alone or in combination with pozelimab, Regeneron’s C5-targeted antibody therapy. Pozelimab is marketed under the brand name Veopoz to treat an ultra-rare immune condition.
A total of 288 adults with gMG who had self-reactive antibodies against AChRs or LRP4 were enrolled. Participants received either cemdisiran alone every three months, monthly cemdisiran plus pozelimab, monthly pozelimab alone, or a placebo.
Top-line, six-month data showed that cemdisiran, alone or with pozelimab, reduced disease severity compared with the placebo, with cemdisiran alone (monotherapy) showing the greatest benefit.
In the recent analysis, the investigators explored whether this reduction in disease severity translated to fewer hospitalizations among the 79 participants who received cemdisiran monotherapy compared with the 72 participants who received the placebo over the same six-month period.
About a third of participants in either group had been hospitalized for gMG in the two years before the study, and 9%-11% had been hospitalized in the past six months. Some 40%-45% had a history of at least one myasthenic crisis, a medical emergency in which weakness affects breathing muscles.
During the trial’s six-month placebo-controlled period, fewer people treated with cemdisiran were hospitalized for at least one day — due to gMG or not — than those given the placebo (3.8% vs. 15.3%), and the mean number of days in the hospital was also lower with the experimental therapy (7.7 vs. 10.8 days per patient).
Moreover, significantly fewer people given cemdisiran than the placebo experienced a myasthenic crisis (3.8% vs. 15.3%) or required rescue therapy for acute symptom worsening (2.5% vs. 15.3%).
There were 13 gMG-related hospitalizations among 11 people in the placebo group, while one person in the cemdisiran group had a single disease-related hospitalization. That hospitalization lasted one day, while the median length of hospital stay was seven days in the placebo group — totaling 92 hospitalization days across the placebo group.
Overall, “fewer participants in the cemdisiran group versus placebo experienced hospitalization for any reason (3 vs. 11), MG-related hospitalization (1 vs. 11), one or more myasthenic crises (3 vs. 11), or the use of rescue therapy (2 vs. 11),” Habib said. “And if hospitalization was necessary, those treated with cemdisiran were there for fewer days versus placebo (1 vs. median of 7; range: 3-15).”
Cemdisiran was also generally well tolerated, according to Habib.
Note: The Myasthenia Gravis News team is providing virtual coverage of the Myasthenia Gravis Foundation of America’s scientific session at the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting on Sept. 29. Go here to see the latest stories from the conference.
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