Novel Schizophrenia Drug Stumbles in Phase 3 Testing

Megan Brooks

October 26, 2018

The novel, once-daily, oral antipsychotic Lu AF35700 (Lundbeck) was not superior to standard antipsychotic therapy in a phase 3 trial of patients with treatment-resistant schizophrenia, the manufacturer has announced.

The DAYBREAK study evaluated the efficacy, safety, and tolerability of Lu AF35700, 10 or 20 mg/day, in comparison with risperidone (Risperdal, Janssen), 4 to 6 mg/day, or olanzapine (multiple brands), 15 to 20 mg/day, in almost 700 adults with treatment-resistant schizophrenia.

This condition "constitutes the highest burden of disease within schizophrenia for patients, their families, and society, and we had with Lu AF35700 hoped to show superiority against conventional therapy," Anders Gersel Pedersen, MD, PhD, executive vice president of research and development at Lundbeck, said in a news release.

"This is a setback for patients with schizophrenia, but we will continue to advance our pipeline of innovative therapies to meet the needs of patients suffering from psychiatric and neurological diseases," added Pedersen.

Safe, but Not Significantly Effective

The 697 participants in DAYBREAK met DSM-5 criteria for schizophrenia. They had experienced ongoing psychotic symptoms and had demonstrated a lack of satisfactory clinical improvement after receiving at least two different antipsychotics given at an adequate dose and duration.

The novel drug showed "good antipsychotic effects" but did not show statistical superiority compared with conventional therapy on the primary endpoint of change in total scores on the Positive and Negative Syndrome Scale, the company said.

Lu AF35700 was well tolerated and safe at doses of 10 mg and 20 mg in the study. No unexpected adverse events were reported.

The company said further analysis of the data is ongoing.

The US Food and Drug Administration granted fast-track status to the drug in November 2015.

Lu AF35700 is an antagonist at dopaminergic, serotonergic, and α-adrenergic receptors, the company explained. Unlike currently available antipsychotics, it has higher affinity for the dopamine D1 receptor than it has for the dopamine D2 receptor.

In treatment-resistant schizophrenia, the higher ratio of dopamine D1 receptor activity vs D2 receptor activity is thought to result in a beneficial efficacy profile and tolerability profile without the troublesome side effects associated with extensive dopamine D2 receptor blockade, such as extrapyramidal symptoms, the manufacturer noted.

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