Morning Rounds: October 5-12

Pharmaceutical Updates

FDA Approves First Once-Monthly Subcutaneous Olanzapine Injection for Schizophrenia

The US Food and Drug Administration (FDA) approved olanzapine extended-release injectable suspension (Weltruza), a once-monthly subcutaneous long-acting injectable for adults with schizophrenia.¹ Doses of 318 mg, 425 mg, and 531 mg correspond to daily oral olanzapine doses of 10 mg, 15 mg, and 20 mg, respectively. Approval rested on the phase 3 SOLARIS trial, in which 675 adults aged 18 to 64 years were randomized over 8 weeks to 1 of 3 monthly doses or placebo, with statistically significant symptom improvement versus placebo. Teva reported that the product requires no loading doses, oral supplementation, or post-injection monitoring, though its safety information states it is unknown whether postinjection delirium/sedation syndrome, reported with another extended-release olanzapine product given intramuscularly, can occur. Among 137 participants treated for at least 48 weeks, mean weight gain from baseline was 5.6 kg, and somnolence, headache, constipation, and injection site reactions were also common.

FDA Clears First Treatment Indicated Specifically for Negative Symptoms of Schizophrenia, a Prescription Digital Therapeutic

The FDA granted 510(k) clearance to Motivista (CT-155), a smartphone-delivered prescription digital therapeutic for negative symptoms of schizophrenia.² It is indicated as an adjunct to clinician-managed outpatient care, including antipsychotic therapy, in patients aged 18 years and older with clinically stable positive symptoms. Motivista is the first FDA-authorized treatment indicated specifically for negative symptoms. In the phase 3 CONVOKE study of 457 adults, Motivista produced a 6.8-point improvement on the Clinical Assessment Interview for Negative Symptoms-Motivation and Pleasure Scale at 16 weeks versus 4.2 points with a digital control (P = .0003), a 2.6-point absolute difference that the company describes as a 62% relative improvement. No serious treatment-related adverse events were reported.

Oral M4 Positive Allosteric Modulator NTX-253 Completes Phase 1 and Moves Into Phase 2 for Schizophrenia

Neurosterix completed phase 1 studies of NTX-253, an oral positive allosteric modulator (PAM) of the muscarinic M4 receptor, and plans to advance it into phase 2 development in schizophrenia.³ The multi-part ascending-dose studies included healthy volunteers and patients with stable schizophrenia. M4 PAMs modulate dopamine signaling indirectly, and the company positions NTX-253 as a means of reducing psychosis symptoms while avoiding the movement disorders and metabolic complications associated with dopamine antagonists. The company has not yet reported efficacy data; phase 2 in patients with schizophrenia will provide the first efficacy and tolerability signal for the compound.

FDA Cites 4 Deaths as Potential Safety Signal for Evenamide, Keeping US Hold on Treatment-Resistant Schizophrenia Trial

Newron Pharmaceuticals reported last week that the FDA identified 4 deaths among evenamide-treated patients across all clinical studies, compared with 1 death among patients receiving placebo, as a potential safety signal, and that the clinical hold on new US enrollment in the phase 3 ENIGMA-TRS 2 trial in treatment-resistant schizophrenia remains in place.⁴ “This news is disappointing given the excitement about the novel mechanism and potential significant benefits of evanamide. However, before drawing any conclusions, we will await the full analysis of the causes of these 4 unfortunate deaths,” said Psychiatric Times editor-in-chief John J. Miller, MD.

The FDA said a fatal arrhythmic mechanism could not be definitively excluded, citing the known risk that some sodium channel blockers may trigger arrhythmias. Investigators judged 3 of the 4 deaths unrelated to evenamide and 1 possibly related because 2 autopsies were inconclusive. Newron reports no pattern of cardiac abnormalities or arrhythmias, notes that evenamide causes a very small QTc shortening with no established risk threshold, and states that a standard screening electrocardiogram does not reliably exclude latent sodium-channel disorders in asymptomatic patients.

References

1. Teva announces U.S. Food and Drug Administration (FDA) approval of Weltruza (olanzapine) for extended-release injectable suspension, as the first and only once-monthly subcutaneous injectable olanzapine for adults with schizophrenia. Press release. October 9, 2026. Accessed October 12, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Announces-U-S--Food-and-Drug-Administration-FDA-Approval-of-WELTRUZA-Olanzapine-For-Extended-Release-Injectable-Suspension-as-the-First-and-Only-Once-Monthly-Subcutaneous-Injectable-Olanzapine-for-Adults-with-Schizophrenia/default.aspx

2. FDA clears Motivista (CT-155), the first authorized treatment for negative schizophrenia symptoms. Press release. October 5, 2026. Accessed October 12, 2026. https://www.globenewswire.com/news-release/2026/10/05/3374959/0/en/fda-clears-motivista-ct-155-the-first-authorized-treatment-for-negative-schizophrenia-symptoms.html

3. Addex spin-out Neurosterix completes phase 1 clinical studies of NTX-253 for schizophrenia. Press release. October 8, 2026. Accessed October 12, 2026. https://www.addextherapeutics.com/en/investors/press-releases/addex-spin-out-neurosterix-completes-phase-1-clinical-studies-ntx-253-schizophrenia/

4. Four deaths prompt FDA safety concerns about novel schizophrenia drug. Press release. October 8, 2026. Accessed October 12, 2026. https://www.medpagetoday.com/psychiatry/schizophrenia/123330