In a monumental move, Karuna Therapeutics sent shockwaves through the medical world as they unveiled their New Drug Application (NDA) for KarXT, a potential game-changer in schizophrenia treatment. If approved, KarXT could rewrite the rulebook as the first new mechanism of action for schizophrenia in over five decades.
The NDA submission for KarXT, a potent agonist targeting muscarinic acetylcholine 1 receptors M1 and M4, boasts the backing of three registrational trials from the groundbreaking EMERGENT program. The results are nothing short of remarkable, with KarXT hitting the primary endpoint in EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials.
This translated into a “statistically significant and clinically meaningful” reduction in the total score on the Positive and Negative Syndrome Scale (PANSS) when compared to a placebo, as confirmed by Karuna’s press release.
But here’s where KarXT truly stands out – it doesn’t just target the positive symptoms of schizophrenia related to psychosis; it tackles the debilitating negative symptoms, including social withdrawal, lack of motivation, and apathy towards everyday interests.
KarXT’s impact extends to both positive and negative symptoms, as evidenced by improvements across the PANSS positive, PANSS negative, and PANSS negative Marder factor subscales, each of which served as secondary endpoints in these groundbreaking trials.
In an exclusive interview with BioSpace, Andrew Miller, the visionary founder and Chief Operating Officer of Karuna, emphasized the safety profile of KarXT. Unlike current antipsychotics notorious for weight gain, metabolic issues, sedation, and motor symptoms, KarXT presents a refreshing change. It offers safety and tolerability with mild-to-moderate GI side effects that are transient and self-resolving.
This NDA submission marks a historic first for Karuna, a company that has steadily risen since its founding in 2009, supported by a significant $42 million Series A financing in August 2018. It’s no surprise that industry leaders like Robert Nelsen of ARCH Venture Partners have hailed Karuna as a potential game-changer in the CNS sector.
Karuna is gearing up for the standard 10- to 12-month review period for KarXT, with the tantalizing possibility of securing a priority review based on the product’s unique differentiators.
Despite recent setbacks in the schizophrenia treatment arena, such as the Phase III failure of Sumitomo Pharma and Otsuka Pharmaceutical’s ulotaront and the termination of Roche’s ralmitaront Phase II trial, competition is fierce.
Cerevel Therapeutics, a fellow Massachusetts-based company, is blazing a trail with emraclidine, a positive allosteric modulator that selectively targets the M4 receptor while mitigating the side effects associated with pan-muscarinic agonists. Emraclidine is currently undergoing Phase II trials, and experts predict staggering combined peak sales for KarXT and emraclidine to reach a remarkable $7 billion.
Acadia Pharmaceuticals, another strong contender, is unleashing pimavanserin, specifically honed to target the negative symptoms of schizophrenia. In a Phase II trial, pimavanserin showcased significant improvements over placebo on the 16-item Negative Symptom Assessment (NSA-16) when combined with existing antipsychotic regimens. The journey continues as pimavanserin advances through the Phase III ADVANCE 2 study, with topline results expected in 2024.
The race to revolutionize schizophrenia treatment has never been more exciting, and Karuna’s KarXT is undoubtedly at the forefront of this medical breakthrough.”