A potential landmark year for schizophrenia treatments has got off to a rocky start, after the US Food and Drug Administration (FDA) declined to approve Minerva Neurosciences’ roluperidone for the treatment of negative symptoms in patients with schizophrenia.

It’s the second snag Minerva has encountered with the FDA, after the agency shunned a review of an initial marketing application for the serotonin, sigma, and α-adrenergic receptor-blocking drug in 2022.

The FDA’s complete response letter raised four clinical decencies from Minerva’s new drug application (NDA), according to a 27 February press release.

Shares in the company slid by over 50% at market open compared to a pre-announcement market close on 26 February.

The FDA alluded to the MIN-101C03 study, saying that although the primary efficacy endpoint met statistical significance, more evidence is needed to back up the drug’s effectiveness. The agency added that more data is needed to demonstrate the improvement patients saw was clinically meaningful.

Other shortcomings included the lack of data on concomitant antipsychotic administration and an inadequate number of subjects exposed to 64mg roluperidone – the proposed dose – for at least a year.

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Minerva’s CEO Dr Remy Luthringer said the biopharma is “disappointed” at the FDA’s rejection, adding that it has requested a meeting with the agency to discuss the feedback.

The company will now need to conduct a further study to address the deficiencies if it wishes to secure FDA approval for the drug. Additional readouts from patients taking the drug alongside antipsychotic medications – used to prove roluperidone’s clinically meaningful benefit – and long-term safety data will also need to be submitted.

Dr Luthringer added: “We believe that roluperidone is a safe and effective therapy for negative symptoms of schizophrenia and we will review FDA’s feedback and consider our potential paths forward, including continuing to work closely with the FDA and providing any additional information as needed.”

Minerva designed roluperidone to not directly block the action of dopaminergic receptors. Dopaminergic receptors are the main target of current antipsychotic therapies for patients with schizophrenia, but this comes with side effects.

Following Minerva’s rejection, all eyes will now be on Karuna Therapeutics, which could have its drug approved for adults with schizophrenia in late 2024. The US biotech’s highly anticipated candidate KarXT (xanomeline-trospium) is a dual M1/M4 muscarinic agonist that could reduce both positive and negative symptoms of the neurological disorder.

Similar to Minerva, Karuna has gone down the “non-dopamine blocking” route.  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.

The promise of Karuna’s treatment is clear, with the company acquired by BMS for $14bn in December 2023.  

There are also key Phase III trial readouts for late-stage schizophrenia candidates in 2024.

Schizophrenia affects around 24 million people globally, according to the World Health Organization. The schizophrenia drug market is forecast to grow to $21.2bn across 68 global markets, according to a 2022 report by GlobalData.

GlobalData is the parent company of Clinical Trials Arena.