Neurocrine Biosciences’ potential competitor to Bristol Myers Squibb’s KarXT improved symptoms of schizophrenia in a Phase II trial, but only at the low dose tested.
Neurocrine Biosciences’ schizophrenia candidate improved symptoms of the psychiatric disorder in a Phase II trial, but only at the lowest dose tested, the company announced Wednesday. However, all other doses failed to meet the study’s primary endpoint.
The mid-stage study assessed the efficacy of NBI-1117568, a potential competitor to Bristol Myers Squibb’s antipsychotic KarXT, which was picked up in the $14 billion acquisition of Karuna Therapeutics late last year and is on the cusp of a landmark FDA decision this fall.
NBI-1117568 met the main goal of improving positive and negative symptoms of schizophrenia with a statistically significant result for the once-daily 20 mg dose at week six, according to Neurocrine. On the Positive and Negative Syndrome Scale (PANSS), the therapy achieved a placebo-adjusted mean reduction of 7.5 points and an 18.2-point reduction from baseline, leading to a p-value of 0.011. This dose also met other endpoints including improving severity of the disorder.
Neurocrine said that the muscarinic M4 selective agonist was generally well tolerated.
But the 30 mg, 40 mg and 60 mg doses all failed to achieve statistical significance on the primary symptom goal.
Based on the 20 mg dose reaching the primary endpoint, Neurocrine plans to advance NBI-1117568 into a Phase III trial in early 2025.
Analysts pointed out that NBI-1117568 underperformed results posted by KarXT, which achieved an 11.6-point placebo-adjusted PANSS reduction in the Phase II EMERGENT-1 trial. Those results declined to an 8 to10 point reduction in a later Phase III study.
But BMO Capital Markets analyst Evan David Seigerman in a Wednesday note to investors said “a path forward in schizophrenia may still exist” for Neurocrine’s asset, which has shown a better safety profile including gastrointestinal tolerability and weight gain symptoms.
“In order for ‘568 to be differentiated in the market, investors will need to see noted improvements in the safety profile,” Seigerman wrote. “Minimal GI effects and no weight gain are positive signs supporting further development.”
However, William Blair analyst Myles Minter flagged a higher rate of sleepiness and dizziness in patients in the 20 mg cohort who received NBI-1117568, with 12.5% reporting the side effects compared to 2.9% and 1.4% in placebo-treated patients, respectively.
Minter predicted that Neurocrine’s stock would suffer on the news that the PANSS score was lower than competitors, and that’s what happened in Wednesday morning trading. Neurocrine’s shares slipped approximately 20%.
“We believe the trial warrants further development, particularly when considering the significant unmet need in schizophrenia and numerous options in the current standard of care dopamine-receptor blocking agent class that have shown mixed efficacy and compliance-limiting adverse events,” Minter wrote.
It’s been decades since a new schizophrenia treatment was approved, and existing options come with tolerability concerns and often weight gain. Still, like Minter, Seigerman contends Neurocrine may be able to find a foothold in the market.
“With today’s results, management appears confident that ‘568’s tolerability profile is differentiated vs. previous agents, or that the market for novel schizophrenia treatments is large enough to support multiple players,” according to Seigerman.
Another potential competitor is AbbVie, which acquired Cerevel late last year for $8.7 billion to get its hands on emraclidine. That therapy posted a 12.7-point and 11.1-point improvement over placebo on the PANSS, respectively.
