Neurocrine's KarXT competitor succeeds in phase 2 schizophrenia trial at lowest dose

Neurocrine Biosciences recently announced results from its phase 2 trial for a schizophrenia treatment, which had a mixed response. The biotech company achieved its desired efficacy level at the lowest dose in the trial, but higher doses did not perform as hoped, causing investor concerns and a significant drop in the company's stock price.

The San Diego-based company aimed to see an eight-point difference between treatment and placebo on the Positive and Negative Syndrome Scale (PANSS). This target was based on similar studies, including a phase 3 trial of Bristol Myers Squibb’s (BMS) KarXT that reported an 8.4% improvement over placebo. Neurocrine's NBI-1117568, a muscarinic M4 selective agonist, showed a statistically significant 7.5-point improvement over placebo at the lowest dose of 20 mg once a day. This figure is within the expected range and suggests benefits to selective M4 agonism compared to KarXT, which targets both M1 and M4 receptors.

However, the results from higher doses were less promising. Patients who received 40 mg or 60 mg once a day or 30 mg twice a day did not show similar levels of efficacy. The placebo-adjusted PANSS reductions in these cohorts ranged from 1.9 to 5.0 points, falling short of the company's target. This inconsistency in results led to a 16% drop in Neurocrine’s stock value, with shares falling to $128 in premarket trading.

Despite these setbacks, Neurocrine remains optimistic. The company plans to advance the 20 mg dose into a phase 3 study early next year and explore additional indications. Their decision is based on the observed improvements in PANSS scores, starting after three weeks of treatment, and other secondary endpoints on different schizophrenia scales. If the 20 mg dose proves to be both safe and effective, NBI-1117568 could become a competitive schizophrenia treatment with fewer gastrointestinal side effects and more convenient dosing compared to rivals.

Analysts from William Blair acknowledged that the trial results were not a definitive success but still see potential for further development. They noted that while the 7.5-point improvement in PANSS scores is below what some investors expected, it is still a positive outcome. The analysts also pointed out the lack of dose response, indicating no improvement with higher or varied doses, which might limit the drug's potential.

In summary, Neurocrine Biosciences’ phase 2 trial of NBI-1117568 for schizophrenia showed promising results at a 20 mg dose but failed to demonstrate efficacy at higher doses. This led to investor skepticism and a significant drop in stock price. However, the company is moving forward with plans for a phase 3 study and remains hopeful about the drug's potential based on the initial data.