Regeneron has reported a phase 3 win in generalized myasthenia gravis (gMG), positioning the pharma to file for FDA approval of its siRNA candidate in the increasingly competitive neuromuscular disease.
The phase 3 trial randomized 190 adults with symptomatic gMG and anti-AChR antibodies to receive one of three regimens. Around one-third of patients received single-agent cemdisiran, a siRNA designed to silence the gene that makes C5 in the liver every 12 weeks. Another third of patients received cemdisiran in combination with pozelimab, a C5 antibody, every 4 weeks. The remaining patients received a placebo.
At Week 24, scores on the MG-ADL measure of gMG symptoms fell 2.3 points on cemdisiran compared to placebo. The figure for the combination arm was -1.74 points. The results were statistically significant, achieving the trial’s primary endpoint. Regeneron reported hits for the monotherapy and combination arms on secondary endpoints.
The cemdisiran primary endpoint data met the expectations Regeneron set in the run-up to the readout. Talking at a TD Cowen event in March, Ryan Crowe, senior vice president for investor relations and strategic analysis at Regeneron, said “anything in the 2s ... would be a great result.”
Regeneron compared the result to clinical trials that linked currently approved C5 inhibitor therapies to placebo-adjusted differences in MG-ADL of -1.6 to -2.1 at 12 to 26 weeks. Argenx won approval for its FcRn-blocker Vyvgart in gMG after showing 68% of people had a 2-point or greater reduction in MG-ADL in the first treatment cycle.
The approval of drugs such as Vyvgart in gMG has put pressure on AstraZeneca’s C5 inhibitor Ultomiris. The Big Pharma has responded with a self-administered subcutaneous nanobody C5 inhibitor that hit its phase 3 goals last month. Regeneron’s cemdisiran has a different mechanism of action than its approved and near-approval rivals.
Speaking in March, Crowe cited the use of cemdisiran to silence C5 production and pozelimab to remove any existing C5 in circulation as a differentiator for Regeneron. Yet, single-agent cemdisiran performed numerically better than the combination across the primary and secondary endpoints. Regeneron plans to seek FDA approval for cemdisiran monotherapy in the first quarter of next year.
Regeneron licensed cemdisiran from Alnylam when it tweaked its deal with the RNA specialist last year. Under the revised deal, Alnylam received $10 million upfront and the chance to pocket a payment if the drug candidate is approved as a monotherapy. A further $325 million in commercial milestones are tied to sales of cemdisiran as a combination product.