Regeneron is eyeing regulatory approval for its subcutaneous generalised myasthenia gravis (gMG) candidate cemdisiran after positive results from a Phase III trial.
The NIMBLE trial evaluated adults with symptomatic gMG who have antibodies to the acetylcholine receptor (anti-AChR). This patient subcategory constitutes 80% of the overall gMG population.
During the NIMBLE study (NCT05070858), the small-interfering RNA (siRNA)-based therapy met its primary endpoint – demonstrating a statistically significant -2.3 change in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores when accounting for placebo-adjusted treatment difference.
This trumps UCB’s Zilbrysq (zilucoplan), as well as both of AstraZeneca’s gMG therapies, namely Ultomiris (ravulizumab) and Soliris (eculizumab), which improved scores by -2.09, -1.7, and -1.9, respectively. However, it failed to outdo the efficacy of UCB’s Rystiggo (rozanolixizumab-noli), which reduced patient MG-ADL values by 2.6.
Cemdisiran also met its key secondary endpoint – improving total Quantitative Myasthenia Gravis (QMG) scores by -4.24 compared with a placebo value of -1.46.
The drug was also seen to be more effective as a monotherapy for myasthenia gravis than in combination with Regeneron’s complement 5 (C5) monoclonal antibody (mAb) Veopoz (pozelimab) – which was being evaluated in the indication after its US approval for CHAPLE disease.
This suggests that cemdisiran could exist as an effective standalone treatment for gMG, reducing the risk of C5 depletion-associated meningococcal infection, a known side effect of Veopoz.
There were two deaths in the extension period of this study. One patient died in the monotherapy treatment arm from pneumonia, while the other death occurred in the combo arm due to septic shock. Regeneron added that the two patients were on concomitant immunosuppressive therapies.
There were no deaths or treatment discontinuations due to adverse events in the 24-week placebo-controlled portion of the trial, however.
The trial results mark a validation of the $10m spent by Regeneron on securing the exclusive global rights to the siRNA from Alnylam Pharmaceuticals in June 2024. This followed Regeneron’s long-term collaboration with Alnylam on cemdisiran’s development.
Cemdisiran’s dosing edge
Following the results of the NIMBLE trial, Regeneron’s cemdisiran could be positioned to become the first siRNA therapy approved for the indication.
Though it did not surpass the efficacy of Rystiggo in terms of MG-ADL score improvements, its administration regimen is more patient-centric, with cemdisiran only requiring a dosage once every four weeks compared with the former, which is dosed once weekly.
Results may be promising, but Regeneron will still have to fight off competition from Johnson & Johnson’s (J&J) neonatal Fc receptor (FcRn) blocker Imaavy (nipocalimab), which was recently granted FDA approval for gMG in April 2025.
Following the FDA’s decision to approve Imaavy in the indication, analysts at GlobalData forecast that the drug will soon reach blockbuster status – raking in $1bn for J&J by 2026 after just one year on the market, with sales increasing to $3.5bn by 2031. J&J predicts an even higher ceiling, forecasting $5bn per year in peak revenues.
Imaavy isn’t the only FcRn blocker that cemdisiran may have to go up against if approved, as Argenx’s Vyvgart (efgartigimod alfa) is available to US patients with gMG, with the company currently exploring a label expansion to patients that are AChR antibody-negative.
Looking to bolster its gMG offerings, AstraZeneca is developing a third gMG candidate called gefurulimab, which met its primary and secondary endpoints in the recent Phase III PREVAIL trial (NCT05556096) when administered subcutaneously once-weekly.
