Shares of Newron Pharmaceuticals SpA (SIX:NWRN) fell more than 71% May 4 on news that sarizotan, its experimental therapy for the rare neurodevelopmental disorder Rett syndrome, failed to meet both the primary and secondary efficacy endpoints of the company's pivotal STARS study, leading it to terminate the program. In March, Newron CEO Stefan Weber called sarizotan's development part of an important year for Newron. Now the company will continue to advance a pipeline led by evenamide in schizophrenia, he said, though progress of a phase III trial of that drug has been delayed amid the COVID-19 pandemic.
Sarizotan was one of just three programs in late-stage testing for Rett syndrome, a genetic disorder that affects girls almost exclusively. With no drug specifically approved for the indication, patients will now have to wait for the outcome of two phase III trials: GW Pharmaceuticals plc's phase III test of cannabidiol, a medicine already marketed for epilepsy and Neuren Pharmaceuticals Ltd.'s trofinetide, partnered with Acadia Pharmaceuticals Inc.
Newron licensed sarizotan from Merck KGaA subsidiary Merck Serono in 2011 as part of a deal the companies struck amidst a years-long relationship. One product of their work, Xadago (safinamide), went on to global approvals as an adjunctive therapy for Parkinson's disease, though Newron has been responsible for it since Merck returned rights in 2012. Development of the other drug licensed in the 2011 deal, pruvanserin, is thought to be discontinued, according to Cortellis.
Newron didn't disclose any specific details of the STARS trial endpoints on Monday. But Chief Medical Officer Ravi Anand said that the team was "very disappointed" with results, which built on years of clinical safety data. That foundation, built initially in Merck's pursuit of sarizotan as a potential treatment for L-dopa-induced dyskinesia in Parkinson's disease, was later bolstered by what Anand called "highly promising data from a genetic model of Rett syndrome in mice." That the STARS trial missed its endpoints is indicative of "the difficulties inherent in translating effects in animal models to human clinical studies," he said.
STARS (Sarizotan for the Treatment of Apneas in Rett Syndrome) enrolled 129 Rett syndrome patients in 14 centers throughout the U.S., Europe, Asia and Australia for a six-month trial. Patients were randomized to receive either a 5-mg twice daily (BID) or 10-mg BID dose of the 5-HT 1a agonist or a placebo, then monitored for the primary endpoint: a percentage reduction in episodes of apnea during waking time compared with placebo. Multiple secondary endpoints included caregiver assessments of efficacy, respiratory symptoms and an overall symptom assessment.
Results of additional explanatory analyses and an analysis of the full dataset will be needed to more fully understand the results, Anand said. Meanwhile, the company will carry ahead with its development of evenamide, the lead from a series of oral sodium channel blockers for the potential treatment of patients with positive symptoms of schizophrenia. Preclinical toxicity findings stalled the program last May. But following FDA agreement on the design and conduct of animal studies intended to address those concerns, the company was expected to return to the clinic to investigate the drug in patients again later this year. Like many of its peers, in March, the Milan, Italy-based company said its evenamide clinical plans would be delayed, though it wasn't certain for how long.
The company is also investigating ralfinamide, another sodium channel blocker, for patients with specific rare pain indications. A representative of Newron didn't return a request for further detail on Monday.