After announcing another late-stage success, Karuna Therapeutics’ much-anticipated treatment for schizophrenia is gaining steam. However, expected U.S. clearance next year isn’t yet a done deal, as evidenced by a secondary endpoint setback.
In August 2022, Karuna announced that its KarXT treatment had been successful in the stage 3 EMERGENT-2 study. New late-stage results from the EMERGENT-3 study are now available. Positive and Negative Syndrome Scale improvements were 8.4 points more than placebo improvements by week 5 in the study of 256 adults.
Positive manifestations of schizophrenia, which include alterations in behavior or thinking processes like delusions or hallucinations, were reduced with KarXT by 3.5 points compared to the placebo, which was a secondary aim of the experiment. Nevertheless, the medicine failed to demonstrate a statistically significant improvement in “negative” symptoms, such as social withdrawal, flat affect, and a lack of interest in interpersonal contacts.
Karuna’s share price could well have slumped because of the secondary endpoint misstep. The biotech’s shares sank almost 8% to $176.51 from the trading price of over $191 on Friday, despite jumping 10% in morning trade.
Having said that, the major success of the study means that Karuna plans to meet with the FDA during the early second quarter and is confident that its scheduled midyear authorization application to the agency is still on schedule.
In addition to the results from EMERGENT-3, information from the active EMERGENT-4 and EMERGENT-5 studies, as well as effectiveness data from the stage two EMERGENT-1 trial and delayed EMERGENT-2 research, will be included in the approval proposal. The PANSS score was reduced by 11.6 and 9.6 points with EMERGENT-1 and EMERGENT-2, respectively, in comparison to the placebo.
Those using KarXT had a 70% higher risk of total care-related emergent adverse outcomes compared to individuals receiving a placebo. Nausea, vomiting, constipation, migraines, diarrhea, and sleeplessness were the most frequently reported adverse effects; however, none of these were considered serious enough to warrant stopping treatment.
CEO Bill Meury stated, “KarXT has now demonstrated a robust and consistent reduction of symptoms across all three registrational trials, providing a compelling picture of the potential of KarXT in schizophrenia. With these data, we are one step closer to a potential treatment option that could provide the first new mechanism of action to treat schizophrenia in several decades.”
Mizuho projected $6.8 billion in maximum sales (not adjusted for risk) for KarXT across multiple applications worldwide by late December 2022. The company thinks the drug might also be useful for treating psychosis associated with Alzheimer’s disease. Karuna is conducting a phase 3 study for the Alzheimer’s application, and there are also two more schizophrenia trials in progress.
Given the magnitude of the challenge and KarXT’s past successes, it’s not surprising that Meury, speaking at the J.P. Morgan Healthcare Conference in January, asserted that KarXT had sufficient financial resources and marketing skills to launch a major medication without the help of a Big Pharma partner.
