The patient death occurred outside the U.S. and was deemed unrelated to Newron Pharmaceuticals’ investigational schizophrenia drug.
Newron Pharmaceuticals has been barred from enrolling more patients into a late-stage study for its schizophrenia therapy for the time being, as the FDA evaluates a patient death.
The pause only applies to Newron’s U.S. sites in the Phase 3 ENIGMA-TRS 2 trial, which is testing the oral glutamate modulator evenamide for treatment-resistant schizophrenia, according to a news release on Wednesday. The death occurred in a study site abroad and was deemed unrelated to evenamide, Newron said.
An independent safety board for Newron’s overall ENIGMA-TRS development program agreed that the company could continue its trials as designed. ENIGMA-TRS 2 is enrolling patients in India and Argentina and is nearing clearance in Colombia and Malaysia. The study remains unencumbered in these countries.
Evenamide is an antipsychotic agent that works by blocking voltage-gated sodium channels, which helps restore the balance of glutamate, a key neurotransmitter involved in excitation, according to Newron’s website. Through this mechanism of action, evenamide helps calm down hyper-excitability across the hippocampus and the brain’s cortical regions.
Phase 2 data in February 2023 showed that evenamide lessens disease severity and psychosis symptoms in patients with schizophrenia—benefits that were maintained through one year of follow-up.
Newron has since taken evenamide into late-stage development. Aside from ENIGMA-TRS 2, the biotech is also running ENIGMA-TRS 1, an ongoing randomized, double-blinded and placebo-controlled study testing twice-daily 15-mg and 30-mg doses of evenamide. This second study aims to enroll at least 600 patients on second-generation antipsychotics across Asia, Europe, Canada and Latin America.
“Patient safety remains our highest priority,” Ravi Anand, Newron’s chief medical officer, said in a prepared statement on Wednesday, noting that the biotech thoroughly assesses all patients enrolled into its evenamide programs.
“In the evenamide development program, to date, there is no increase in the risk of mortality between evenamide and placebo-treated patients based on the duration of treatment. Sudden death is not uncommon in patients with schizophrenia,” Anand added.
Schizophrenia is a difficult space for biopharma—both clinically and commercially. In April of last year, for instance, Bristol Myers Squibb’s FDA-approved schizophrenia drug flunked the Phase 3 ARISE study, failing to elicit significant symptomatic improvements versus placebo when used in the adjunct setting. Later that year, in October, the pharma reported third quarter Cobenfy earnings of $43 million, failing to meet investor expectations.
The miss, BMS said at the time, was due to “deeply ingrained” prescribing philosophies that the company hoped to change through education.
