Just today, Bristol-Myers Squibb announced that it had failed to achieve the primary endpoint of its phase 3 ARISE trial, which was evaluating the use of COBENFY as an adjunctive treatment with atypical antipsychotics in adults with inadequately controlled symptoms of schizophrenia.

The hope was that this drug given alongside atypical antipsychotics would allow such patients to respond. These aren’t your typical schizophrenia patients. These are patients of the type who, despite receiving such antipsychotics, don’t respond to them. In essence, they don’t achieve relief in symptoms.

In order to measure this outcome, there is a score used known as the Positive and Negative Syndrome Scale (PANSS) total score, which was the primary endpoint. This score is important because it measures symptom severity of a patient’s disease. The higher this score is, the worse off a patient is in terms of ongoing symptoms.

It was noted that COBENFY, given alongside atypical antipsychotics in these adults with uncontrolled schizophrenia, achieved a change in PANSS total score of -14.3 points. However, placebo achieved a PANSS total score of -12.2 points. The end result was a difference of 2 points, whereby a non-statistically significant p-value of p=0.11 was revealed.

This outcome was evaluated over a 6-week period, and unfortunately, COBENFY given alongside such atypical antipsychotics didn’t achieve the desired outcome. This particular M1/M4 muscarinic receptor agonist was previously known as KarXT, when it was being developed by Karuna Therapeutics for the treatment of patients with Schizophrenia.

However, Bristol-Myers Squibb was able to add COBENFY to its pipeline when it spent roughly $14 billion to acquire Karuna Therapeutics. Not all is lost, though for this big pharma, because this was just to see if it could expand its label to include this drug being given as an adjunctive therapy to atypical antipsychotics.

This drug had already been approved by the FDA in September of 2023 for the treatment of adults with schizophrenia. Such regulatory approval from this U.S. agency was given on the basis of meeting the primary endpoint in two identical studies, known as Study 1 and Study 2. Both of these trials evaluated COBENFY with the primary endpoint of change from baseline in PANSS total score over a 5-week period. In this instance, the drug was shown to achieve a significant improvement over placebo in terms of reducing symptom severity.

A good thing about COBENFY, though for Bristol is that it is not a drug only developed for one psychiatric condition. It is also in development for symptoms of Alzheimer’s disease, autism spectrum disorder and bipolar disorder. Plus, other conditions of this caliber with unmet medical need.

Separately, there is another pharmaceutical company by the name of Neurocrine Biosciences, which is evaluating the use of valbenazine as an adjunctive treatment for patients with schizophrenia who have an inadequate response to antipsychotic treatment. It is gearing up to report topline results from its phase 3 study using this drug for this patient population in 2025.