Karuna’s Schizophrenia Drug Meets Primary Endpoint in Clinical Trial

Karuna Therapeutics has announced positive results from its Phase 2 clinical trial of KarXT for the treatment of acute psychosis in patients with schizophrenia.

“The schizophrenia treatment landscape has remained rather stagnant for decades with therapeutic options relying on discoveries dating back to the 1950s,” said Steve Paul, M.D., chief executive officer, president, and chairman of Karuna. “KarXT and its novel muscarinic receptor mechanism of action represent the potential to become a true advancement in how schizophrenia is treated, allowing patients relief from their debilitating psychotic symptoms without experiencing some of the very troubling side effects associated with current treatments.”

Muscarinic acetylcholine receptors emerged in the 1990s as a promising alternative target to dopamine-receptor based treatments for treating psychosis, but adverse side effects limited their development as a therapeutic option. It is believed that these side effects were the result of the stimulation of muscarinic receptors in peripheral tissues. Karuna addressed this issue by combining xanomeline, a novel muscarinic receptor agonist that preferentially stimulates M1 and M4 muscarinic receptors, with trospium, an approved muscarinic receptor antagonist that does not measurably cross the blood-brain barrier, confining its effects to peripheral tissues. The resulting therapeutic, known as KarXT, was designed to activate muscarinic receptors in the CNS while avoiding the side effects associated with activating muscarinic receptors in peripheral tissues.

Schizophrenia is characterized by recurring episodes of psychosis requiring long-term treatment with antipsychotic drugs in most patients. It affects more than 21 million people worldwide and 2.7 million Americans. At least one-third of patients with schizophrenia fail to respond to current treatments, with 74% of patients discontinuing within 18 months of initiation. People with schizophrenia have a 10- to 15-year reduction in life expectancy and struggle to maintain meaningful interpersonal relationships. The World Health Organization ranks psychosis as the third-most disabling medical condition in the world. (Source: Karuna Therapeutics Website, 18 November, 2019)