A Regeneron Pharmaceuticals drug that lowers levels of a disease-driving protein has met the goals of a pivotal test in the rare disease generalized myasthenia gravis. Based on these results, Regeneron plans to seek FDA approval for the therapy, potentially introducing a new mechanism of action to the increasingly competitive field of treatments for this neuromuscular disorder.
The Regeneron drug, cemdisiran, takes a new approach to the treatment of myasthenia gravis, a disease that leads to difficulty swallowing as well as muscle weakness. The autoimmune disorder develops as the body attacks proteins key to communication between nerves and muscles. Abnormal antibodies produced by the body activate the complement system, a part of the immune system. Cemdisiran is a small interfering RNA (siRNA) drug designed to reduce circulating levels of the complement system protein C5.
In topline results from the 24-week placebo-controlled Phase 3 study, Regeneron said Tuesday that cemdisiran as a monotherapy led to an average 74% inhibition of complement activity. The trial also evaluated the combination of cemdisiran with Regeneron’s approved C5 inhibitor pozelimab, brand name Veopoz. The combination achieved even inhibition of the complement system, with Regeneron reporting the drug pairing led to a nearly 99% inhibition of complement activity.
Nevertheless, the trial’s main goal is measuring the change in score according to a scale that measures activities of daily functioning. On this measure, cemdisiran monotherapy showed numerically better scores, which indicates greater symptom improvement and better treatment effect. Regeneron executives said the results indicate it might not be necessary to completely block complement system activity.
“The potential for best-in-class efficacy with less than complete complement blockade with cemdisiran monotherapy may also provide for a more favorable safety profile,” Regeneron President and Chief Scientific Officer George Yancopoulos said in a prepared statement. “These exciting results highlight the transformative potential of our siRNA and genetic medicines pipeline to deliver paradigm-changing therapies for patients.”
Regeneron said detailed results from the Phase 3 study will be presented at an upcoming medical meeting. Pending discussions with the FDA, the company plans a U.S. regulatory submission in the first quarter of next year.
Myasthenia gravis has welcomed several new drugs in recent years. Argenx’s Vyvgart, approved in 2021, is an antibody fragment designed to block the neonatal Fc receptor (FcRN), leading to degradation of disease-driving autoantibodies by the cell’s built-in disposal system. UCB has two myasthenia gravis drugs, the FcRn-blocking antibody Rystiggo and the C5 inhibitor Zilbrysq, both approved in 2023. Myasthenia gravis is also one of the indications for the blockbuster AstraZeneca C5 inhibitors Soliris and Ultomiris. The newest myasthenia gravis drug is Johnson & Johnson’s Imaavy, an FcRn-blocking antibody awarded FDA approval in May.
In a note sent to investors, Leerink Partners analyst David Risinger said that while differences in clinical studies make cross-trial comparisons difficult, the efficacy results for Regeneron’s drug fall short of the drugs that block FcRn. But he added that the Regeneron drug’s results were roughly comparable to AstraZeneca’s C5 inhibitors, and cemdisiran could stand out here.
C5 inhibitors come with requirements that make them burdensome compared to other myasthenia gravis therapies. The AstraZeneca drugs are only approved for patients who test positive for a particular type of disease-driving antibody, anti-acetylcholine receptor antibodies, Risinger said. Inhibiting the complement system raises the risk of potentially fatal meningococcal infections. That risk is flagged in a black box warning that advises meningococcal vaccination at least two week prior to taking a C5 inhibitor. Furthermore, C5 inhibitors are only available through a risk evaluation and mitigation strategy (REMS) program that manages the risks of these therapies.
Cemdisiran comes from RNA interference specialist Alnylam Pharmaceuticals. Regeneron licensed global rights to develop the siRNA drug by itself and in combination with C5-blocking antibodies. Alnylam is entitled to receive regulatory milestone payments and royalties from sales of an approved product.
Photo: Michael Nagle/Bloomberg, via Getty Images
