Karuna Therapeutics, Inc. has announced positive topline results from its phase 3 EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium) in adults with schizophrenia.
The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 8.4-point reduction in positive and negative syndrome scale (PANSS) total score compared to placebo at Week 5.
Consistent with prior trials, KarXT demonstrated an early and sustained statistically significant reduction of symptoms from Week 2 through the end of the trial as assessed by PANSS total score.
“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,” said Bill Meury, president and chief executive officer of Karuna Therapeutics.
“We look forward to working closely with the FDA as we focus our attention on the regulatory process, including our upcoming pre-NDA meeting in early second quarter, and remain on track for an NDA submission in mid-2023.”
“Schizophrenia is a persistent and disabling condition that presents with symptoms which are often difficult to treat and manage. Despite the number of currently available treatments, there remains a significant need for new treatment options for the 21 million people living worldwide with schizophrenia,” said David Walling, chief clinical officer at Cenexel – CNS and investigator on the EMERGENT-3 trial.
“The results from the EMERGENT-3 trial add to the growing body of data which suggest KarXT could address the symptoms of schizophrenia without the common side effects we see with current treatment options.”
KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative Marder factor subscales – secondary endpoints in the trial.
Karuna Therapeutics to submit NDA in mid-2023
KarXT demonstrated a clinically meaningful and statistically significant 3.5-point reduction in PANSS positive subscale compared to placebo at Week 5. While not meeting the threshold for statistical significance at Week 5, KarXT did demonstrate a statistically significant reduction in PANSS negative subscale and PANSS negative Marder factor subscale compared to placebo at Week 4.
The NDA submission for KarXT in schizophrenia will incorporate the efficacy and safety data from the three placebo-controlled registrational trials, EMERGENT-1, EMERGENT-2, and EMERGENT-3, in addition to long-term safety data from the ongoing EMERGENT-4 and EMERGENT-5 trials. The company is on track to submit an NDA to the FDA in mid-2023, with a potential launch in the second half of 2024, if approved.
Karuna Therapeutics’ EMERGENT-3 trial
The phase 3 EMERGENT-3 trial is a double-blind, placebo-controlled, five-week, inpatient trial evaluating the efficacy, safety, and tolerability of their lead investigational therapy, KarXT, compared to placebo in adults with schizophrenia in the U.S. and Ukraine.
A total of 256 adults (between the ages of 18 and 65 years) with schizophrenia enrolled in the trial. Enrolled patients had a confirmed diagnosis of schizophrenia and were experiencing symptoms of psychosis at the time of enrollment.
The company also announced positive results from its EMERGENT-2 trial last year.
KarXT (xanomeline-trospium) is an oral, investigational M1/M4-preferring muscarinic agonist in development for the treatment of psychiatric and neurological conditions, including schizophrenia and psychosis in Alzheimer’s disease.
KarXT is the first potential medicine of its kind with a truly new and unique dual mechanism of action. Unlike current therapies, KarXT does not rely on the dopaminergic or serotonergic pathways, and it is designed to harness the therapeutic potential of xanomeline while managing peripheral side effects through trospium.
This approach has the potential to provide a differentiated therapy, and, if approved, to beneficially impact the lives of millions of people with serious mental illness.