The US Food and Drug Administration (FDA) has placed a clinical hold on the Phase I trial of Neumora Therapeutics’ schizophrenia therapy, NMRA-266.
The decision for the clinical hold was based on the preclinical data for NMRA-266 showing that the drug triggered convulsions in rabbits.
Following the news, Neumora’s stack was down by 17.48% at the market close on 15 April, compared to the market close on 12 April. The company’s market cap stands at $1.78bn.
Neumora initiated the Phase I trial for NMRA-266 evaluating the drug’s safety in healthy volunteers in November 2023. Approximately 30 participants were dosed in the single/multiple ascending dose trial when the US FDA placed the clinical hold. The company was quick to add that ‘no evidence of convulsions was observed in any participant’.
Adding that the company is ‘working with the FDA to evaluate the potential to resolve the clinical hold’.
NMRA-266 is a positive allosteric modulator (PAM) of the M4 muscarinic receptor. NMRA-266 was Neumora’s lead candidate. The company expected data from the Phase I trial in mid-2024, with the initiation of the Phase Ib study expected in H2 this year.
Various companies have invested in developing therapies for schizophrenia. One of the most anticipated therapies in the field is Karuna Therapeutics’ KarXT (xanomeline-trospium), which is a dual M1/M4 muscarinic agonist that could reduce both positive and negative symptoms of the neurological disorder. The Prescription Drug User Fee Act (PDUFA) date for KarXT is 26 September 2024. If approved, the drug would represent a new class of medication on offer to those with schizophrenia.
Neumora’s pipeline consists of various candidates for neuropsychiatric disorders and neurodegenerative diseases. The company’s most advanced clinical drug is navacaprant (NMRA-140), a selective once-daily kappa opioid receptor (KOR) antagonist. The drug is being evaluated as a treatment for major depressive disorder (MDD) in multiple Phase III KOSTAL trials.
The topline data from the randomised, placebo-controlled Phase III KOSTAL-1 trial (NCT06029426) in H2 2024. The topline data from the two other replicate Phase III trials (NCT06058039 and NCT06058013) in H1 of 2025. Neurmora is also planning to investigate navacaprant as a treatment for bipolar depression, with a Phase II trial slated for initiation in H1 this year.
With navacaprant being an opioid, there was a concern that patients may develop dependence. However, the company received feedback from the FDA that ‘there is no need for the company to conduct further studies to assess physical dependence with navacaprant’, following a type D meeting with the agency in February.
