US regulators have pressed pause on enrolment to Newron Pharmaceuticals’ Phase III trial on lead schizophrenia candidate, evenamide, after a patient death.
The US Food and Drug Administration (FDA) put the late-stage ENIGMA-TRS 2 study (NCT04461119) of evenamide in treatment-resistant schizophrenia (TRS) on ice after Newron informed the agency of a study participant’s sudden death, which occurred at a clinical site outside of the US. Newron has not publicly disclosed the cause of this patient’s death.
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While an investigator deemed this fatality unrelated to the study treatment, the ENIGMA-TRS 2 trial will remain on hold, pending review from the FDA.
After this event, Newron has talked with the independent international safety monitoring board for the ENIGMA-TRS programme, which includes both the paused trial and the ENIGMA TRS 1 study (EUCT2024-519836-18-00), which is recommending that the studies forge on as originally designed.
Amid the pause on US enrolment for the second ENIGMA-TRS trial, the first study will continue, which has enrolled more than 400 patients across 21 countries.
In a 29 April statement, Newron’s CMO, Ravi Anand, noted that in the evenamide development programme, to date “there is no increase in the risk of mortality between the drug- and placebo-treated patients based on the duration of treatment”, and that sudden death is “unfortunately not uncommon in patients with schizophrenia”.
Evenamide, also known as NW-3509, is a first-in-class, add-on antipsychotic pill for TRS. The drug acts through the modulation of glutamate, differing from approved alternatives that tend to target dopamine.
Unmet needs in schizophrenia persist
While several treatments have now reached the schizophrenia market, researchers estimate that around 30% of patients have treatment-resistant disease.
TRS is an area of notable unmet need, as there is currently only one FDA-approved medicine, clozapine, that is specifically approved for the indication. Clozapine first secured the regulatory greenlight nearly four decades ago.
Across the wider schizophrenia research space, there are currently 57 ongoing Phase III trials. This includes a study (NCT06229210) of the long-acting formulation of Johnson & Johnson’s (J&J) Caplyta (lumateperone), which is assessing the drug’s safety and tolerability in paediatric patients with either schizophrenia, bipolar or autism spectrum disorder. Just a few days ago, the FDA greenlit a label expansion for Caplyta in schizophrenia, deeming the drug suitable for the prevention of relapse within the disease.
Meanwhile, Bristol Myers Squibb’s (BMS) Cobenfy (xanomeline/trospium chloride) became the latest drug to secure the US regulatory go-ahead, though its initial uptake has been slow due to insurance challenges and reluctance from some psychiatrists to prescribe it, as per an article from Bloomberg.
