Regeneron's RNA Med meets trial goals; plans to be planned for next year's FDA filing
Recovery drugs that reduce disease kinesin levels meet the goals of key tests in rare diseases. Based on these results, Regeneron plans to seek FDA approval for treatment and has the potential to introduce new mechanisms of action into the increasingly competitive therapeutic area of neuromuscular diseases.
Regeneron drug Cemdisiran has taken a new approach to treating Gravis of muscle weakness, a disease that causes dysphagia and muscle weakness. Autoimmune diseases can attack proteins as the body attacks, which is the key to communication between nerves and muscles. Abnormal antibodies produced by the body activate the complement system, which is part of the immune system. Cemdisiran is a small interfering RNA (siRNA) drug designed to reduce the circulating levels of protein C5 in the complement system.
Regeneron said Tuesday that in the results of the 24-week placebo-controlled phase 3 study, Cemdisiran as a single treatment resulted in an average of 74% inhibitory effect on complement activity. The trial also evaluated the binding of Cemdisiran with Regeneron-approved C5 inhibitor Pozelimab (brand Veopoz). Even inhibition of the complement system reached a consolidation, while Regeneron reported that drug pairing resulted in nearly 99% inhibition of complement activity.
However, the main goal of the trial was to measure score changes based on a scale that measured daily functional activities. On this measure, CEMDISIRAN monotherapy showed better scores numerically, indicating improved symptoms and better treatment effects. Regeneron executives said the results suggest that there may be no need to completely block the complement system activity.
“The full complementary lockdown with Cemdisiran monotherapy, with the potential of first-class efficacy, may also provide more favorable safety,” George Yancopoulos, president and chief scientific officer of Regeneron, said in a prepared statement. “These exciting results highlight the transformative potential of our siRNA and genetic drug pipelines that can provide patients with paradigm-changing therapies.”
Regeneron said detailed results from the Phase 3 study will be presented at the upcoming medical conference. The company plans to conduct U.S. regulatory submissions in the first quarter of next year before discussing with the FDA.
In recent years, Gravis, who has weak muscles, has welcomed several new drugs. Argenx's Vyvgart was approved in 2021 and is an antibody fragment designed to block neonatal FC receptors (FCRNs), resulting in the degradation of autoantibodies for the disease by the built-in cell processing system. UCB has two Gravis drugs for muscle weakness, the FCRN blocking antibody Rystiggo and the C5 inhibitor Zilbrysq, both approved in 2023. Myasthenia is Gravis' muscle weakness and is one of the indicators of the sensational Astrazeneca C5 C5 inhibitors Soliris and Ultomiris. The latest Gravis drug for muscle weakness is Johnson & Johnson's Imaavy, an FCRN blocking antibody that received FDA approval in May.
Leerink Partners analyst David Risinger said in a note sent to investors that although differences in clinical studies make cross-trial comparisons difficult, the efficacy results of the Regeneron drug did not block FCRN drugs. But he added that the results of the Rejarent drug are roughly comparable to AstraZeneca’s C5 inhibitor, where cemdisiran can stand out.
The requirements of C5 inhibitors make it heavy compared to other myostria therapies for muscle weakness. Risinger said AstraZeneca drugs are only approved for testing specific types of disease antibodies, patients with anti-acetylcholine receptor antibodies. Inhibition of the complement system increases the risk of potentially fatal meningococcal infection. The risk is marked in a black box warning that recommends getting the meningococcal vaccination at least two weeks before taking the C5 inhibitor. In addition, C5 inhibitors can be used to manage the risks of these therapies only through the Risk Assessment and Mitigation Strategies (REMS) program.
Cemdisiran comes from RNA interference expert Alnylam Pharmaceuticals. Regeneron authorizes the global right to develop siRNA drugs on its own and use them in combination with C5 blocking antibodies. Alnylam is entitled to regulatory milestone payments and royalties in the sale of approved products.
Photo: Michael Nagle/Bloomberg, by Getty Images
