Newron Pharmaceuticals will terminate work on its experimental Rett syndrome drug sarizotan after a complete failure in its pivotal STARS trial.
This study was assessing sarizotan, originally developed by Germany’s Merck, in Rett syndrome, a severe neurodevelopmental disorder primarily affecting women.
The pivotal STARS study, in which Newron was predominantly assessing its med in respiratory issues arising from the disease, did not meet “primary or secondary efficacy variables,” the U.S.-Italian biotech said.
Details and numbers were scarce, but the company said the primary endpoint was a percentage reduction in episodes of apnea during waking time compared with placebo, which it didn’t hit.
Given this failure, Newron will now cull the drug, which worked as a highly selective compound for specific serotonin or dopamine receptors that modulates the activity of these neurotransmitters in the brain. It was gunning to be the first med to treat Rett syndrome.
It will also now “prioritize its phase 3 development program of evenamide in schizophrenia and evaluate additional pipeline candidates” in light of the flop.
That drug has had its own issues, however: Last summer, Newron delayed the start of phase 2/3 schizophrenia studies in evenamide at the request of the FDA. The agency requested the delay after seeing data from studies of evenamide in mice and dogs.
The drug, an oral selective glutamate inhibitor, came through an 89-patient phase 2a trial in 2017 without setting off any safety alarms. And, with the trial linking evenamide to improvements on a scale of schizophrenia symptom severity, Newron planned to start a pair of phase 2/3 trials designed to support regulatory authorizations. The trials were due to start in the second quarter of 2019.
At the time, Newron attributed the delay to a communication from the FDA indicating concerns with the findings of a recently completed study in rats and the central nervous system events seen in dogs that received higher doses of evenamide.
Since then, Newron and the FDA “have agreed on the design and conduct of explanatory studies with evenamide required to address previously announced potential safety issues raised by the FDA, including a four-week explanatory study in patients with schizophrenia; initial results in rats and humans are expected in Q3 2020,” it said in a recent corporate update, although it said that COVID-19 has hampered timelines here.
If these come through, Newron added that it “intends to commence its proposed phase 3 clinical trial program with evenamide comprising of two efficacy studies.”
Ravi Anand, M.D., chief medical officer at Newron, said: “We are very disappointed that the top-line results in the STARS study did not meet the study endpoints. The results of this well designed and executed study, based on highly promising data from a genetic model of Rett syndrome in mice, indicate the difficulties inherent in translating effects in animal models to human clinical studies. We are currently awaiting results of additional explanatory analyses and will continue to analyse the full data set from the study to understand more about the results.”
Stefan Weber, Newron’s chief, added: “Newron continues to develop its pipeline and evaluate additional candidates, consistent with its long-term strategy of developing novel therapies for patients with diseases of the central and peripheral nervous system. In the near term, we look forward to progressing our phase 3 clinical program evaluating Evenamide in schizophrenia.”
Shares in the biotech were in free fall on the news, down 76% early Monday morning on the SIX Swiss Exchange.