Regeneron recently announced exciting results from a Phase III clinical trial called NIMBLE, evaluating the efficacy and safety of pozelimab + cemdisiran combination therapy and cemdisiran monotherapy for adult patients living with generalized myasthenia gravis (gMG). The results showed that both cemdisiran monotherapy and pozelimab + cemdisiran combination therapy met their primary endpoints, displaying a significant improvement over 24 weeks, as measured by reductions in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale score. This means that pozelimab and cemdisiran combination has the potential to challenge currently marketed disease-modifying therapies (DMTs), says GlobalData, a leading data and analytics company.
Jos Opdenakker, Neurology Analyst at GlobalData, comments: “Regeneron’s pozelimab and Alnylam Pharmaceuticals’ cemdisiran work through mediating C5 complement inhibition. C5 is a protein that is thought to be involved in the damage of acetylcholine receptors and is a frequent target of DMTs within the MG treatment landscape. In the NIMBLE trial, the results were statistically significant, achieving the trial’s primary endpoint of a significant improvement in MG-ADL score.”
Opdenakker adds: “As a DMT, pozelimab + cemdisiran would be entering a highly competitive space in the market, as they are treatments targeting the AChR+ MG patient population, the most common form of MG. Furthermore, they are complement inhibitors, which is a well-established treatment pathway in the MG treatment paradigm.”
According to GlobalData’s drugs database, there are six DMTs currently marketed across the seven major pharmaceutical markets (7MM*) for AChR+ patients. Of these six DMTs, three are complement inhibitors, Soliris (eculizumab), Ultomiris (ravulizumab), and Zilbrysq (zilucoplan). Key opinion leaders (KOLs) previously interviewed by GlobalData have stated that there may not be much additional room in the MG market for another anti-complement agent, and that the combination of pozelimab + cemdisiran would have to display efficacy over existing anti-complement treatments in order to prompt clinicians to switch to this new combination therapy.
Opdenakker continues: “Pozelimab + cemdisiran may also have an added advantage over existing treatments, in that the NIMBLE trial sought to recruit patients who were LRP4+.”
KOLs interviewed by GlobalData have noted that there is a significant unmet need for effective treatments targeting the LRP4+ patient population. Currently, there is no effective DMT on the market that targets the LRP4+ MG population, which means that Regeneron can position pozelimab + cemdisiran to meet this unmet need. Another advantage that Regeneron and Alnylam possess is that cemdisiran’s promising results versus placebo could also open the door for it to be used as a monotherapy.
Opdenakker states: “If cemdisiran was to be approved as a monotherapy, this could alleviate some of the financial constraints surrounding the use of this DMT. However, the approval of cemdisiran as a monotherapy would have to be carefully considered by both Regeneron and Alnylam, who are co-developing the pozelimab + cemdisiran combination therapy. Developing cemdisiran as a monotherapy may bring potential complications from a co-marketing perspective and could jeopardize their strategic alliance.”
GlobalData forecasts that pozelimab + cemdisiran combination therapy could drive sales of approximately $1.9 billion by 2034 in the 7MM as one of the promising pipeline products given its superior comparative efficacy and targeting of the overlooked LRP4+ MG patient segment.
Opdenakker concludes: “The Phase III clinical trial results for pozelimab + cemdisiran mark a significant milestone in the treatment of gMG. With clinically meaningful improvements in the MG-ADL score, pozelimab + cemdisiran offers hope for both AChR+ and LRP4+ patients. However, Regeneron and Alnylam face challenges as they are entering a highly competitive market filled with established DMTs and must ensure that their marketing strategies are aligned in order to facilitate a successful launch.
“The pozelimab + cemdisiran combination therapy 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.”
*7MM: The US, France, Germany, Italy, Spain, the UK, and Japan
