Regeneron’s Phase III generalised myasthenia gravis (gMG) trial shows high disease control potential of cemdisiran.
The Phase III NIMBLE study (NCT05070858) evaluated cemdisiran and pozelimab in patients with gMG.
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The trial sought to evaluate subcutaneously administered cemdisiran and pozelimab as monotherapies or in combination in participants with generalised MG (Myasthenia Gravis Foundation of America [MGFA] Class II–V) who are acetylcholine receptor antibody-positive (AChR+) and/or low-density lipoprotein receptor-related protein 4-positive (LRP4+).
The trial met its primary endpoint, which was a change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL), at week 24, as well as key secondary endpoints, including a change in baseline in the Quantitative Myasthenia Gravis (QMG) score at week 24.
Cemdisiran is a subcutaneously administered investigational therapeutic that uses small interfering RNA (siRNA) technology and is designed to lower circulating levels of complement component 5 (C5) protein in the body by blocking the genetic instructions cells use to make C5.
NIMBLE is a Phase III, randomised, double-blinded, placebo-controlled, four-arm trial (cemdisiran 600mg every 12 weeks, pozelimab 200mg every four weeks, cemdisiran 200mg + pozelimab 200mg, and placebo), and the data highlighted the effectiveness of cemdisiran as a monotherapy. The data showed that the cemdisiran arm of the trial saw a change in baseline at week 24 in MG-ADL total score of -4.5 and achieved terminal complement inhibition of 76.6%. Likewise, cemdisiran elicited a change in baseline at week 24 in QMG total score of -4.2.
Clinically meaningful improvements occurred within two weeks of treatment initiation and were sustained throughout the 24-week double-blinded treatment period. Cemdisiran monotherapy achieved robust efficacy while preserving residual complement activity, with no waning of efficacy throughout the dosing interval. Cemdisiran monotherapy was generally well-tolerated, and no serious infections were reported. The cemdisiran + pozelimab combination therapy was also found to have no additional benefit over cemdisiran monotherapy.
The NIMBLE trial sought to recruit patients who were LRP4+. Key opinion leaders (KOLs) previously interviewed by GlobalData noted that there is a significant unmet need for effective treatments targeting the LRP4+ patient population. Currently, there is no effective disease-modifying therapy (DMT) on the market that targets the LRP4+ MG population; Cemdisiran’s promising results open the door for it to be used as a monotherapy, which means that Regeneron can position cemdisiran to meet this unmet need.
In June 2024, Regeneron and Alnylam entered into an amended and restated C5 License Agreement, which granted Regeneron a worldwide license to cemdisiran as a monotherapy in addition to a license to cemdisiran in combination with C5 antibodies. Regeneron is responsible for the development, manufacturing, and commercialisation of cemdisiran as a monotherapy and in combination with C5 antibodies.
GlobalData forecasts that the pozelimab + cemdisiran combination therapy could drive sales of approximately $1.9bn by 2034 in the seven major pharmaceutical markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan), driven by its targeting of multiple MG subtypes, including AChR+ patients and the overlooked LRP4+ MG patient segment. Cemdisiran would also present a novel mechanism of action, targeting c5 messenger RNA in the liver, which sets it apart from other c5 attenuating therapies.
GlobalData is the parent company of Clinical Trials Arena.
The Phase III clinical trial results for cemdisiran mark a significant milestone in the treatment of gMG. With clinically meaningful improvements in the MG-ADL score and QMG, as well as meaningful safety data, cemdisiran offers hope for both AChR+ and LRP4+ patients.
Cemdisiran monotherapy has the potential to become a valuable addition to the gMG treatment paradigm, offering new possibilities for disease management, should Regeneron be able to successfully navigate the complexities of market competition and opt for a congruent marketing strategy.
Editor’s note: This article has been updated to reflect that the partnership between Regeneron and Alnylam is not impacted by the monotherapy. TEAEs are being investigated as a safety measure. It has also been updated to reflect that Regeneron has not filed for approval for the combination therapy in gMG. The mechanism of action for cemdisiran has also been updated.
