Treatment combining prazosin and cyproheptadine shown to halve alcohol consumption amongst heavy drinkers in three months

Kinnov Therapeutics’ phase II study for its lead compound KT-110 has shown that the treatment can halve alcohol consumption amongst heavy drinkers in three months, with results of the trial published in the peer-reviewed journal Addiction.

The multi-centre, randomised, double-blind, placebo-controlled Phase II clinical trial included 154 patients suffering from severe alcoholism and was conducted in 32 investigating centres across France. The primary endpoints were reduction in alcohol consumption and the secondary endpoints were the number of days of high consumption (HDD), cravings, and depression.

The trial showed that KT-110 has superior efficacy in significantly reducing alcohol consumption in heavy drinkers by 24 grams per day and 30 grams in very heavy drinkers over three months compared to the placebo. A higher dose combination was associated with a larger magnitude of drinking reduction than a lower dose combination, whilst showing a similar safety profile.

Designed by Kinnov Therapeutics and protected by a composition-of-matter patent, KT-110 is based on the pharmacological concept proposed by Pr. Jean Paul Tassin at INSERM and Collège de France, Paris.

KT-110’s mode of action is novel to Alcohol Use Disorder (AUD) and works by simultaneously modulating the noradrenergic and serotonergic brain receptors that counteract the neurobiological processes involved in addiction by regulating the secretion of dopamine. KT-110 which is protected by a composition of matter patent combines two well-known drugs (cyproheptadine and prazosin) that act on these key receptors. By regulating the brain’s reward circuit, KT-110 allows patients to regain control of their alcohol consumption, to significantly reduce or even stop it. KT-110 will be deliverable in a proprietary once-daily tablet formulation.

Professor Henri Jean Aubin, the Principal Investigator of the KT-110 study emphasises the critical need for diversifying the therapeutic options available for managing patients with alcohol dependency: "Addressing alcohol dependency remains a formidable challenge, and expanding our therapeutic toolkit is of utmost importance. KT-110, with its innovative mode of action, signals the emergence of a promising new approach to treatment. The study provides compelling evidence of KT-110's effectiveness and tolerability, as demonstrated by its positive results on the primary endpoint and most secondary endpoints. The effect size observed is notably superior to that of currently available treatments for Alcohol Use Disorder (AUD). I am confident that future phase III trials will further validate these findings, ultimately granting patients access to this innovative treatment option."

Professor Alain Puech, Medical Director of Kinnov Therapeutics, says: "Kinnov Therapeutics has been working for ten years on the development of a new treatment with a unique and original mode of action. The simultaneous modification of two receptors (5HT2a and alpha1b) allows the patient to regain control of their consumption. The phase II pilot trial aimed at providing clinical proof of this new therapeutic concept clearly shows that KT-110 provides patients with a significant improvement in the parameters of alcohol addiction (alcohol consumption, number of heavy drinking days), with reduction figures higher than those reported by existing treatments, in a context of good tolerance. The quality of proof we provide with the study makes us confident in the capacity to reproduce those results in phase III. The development of KT-110 will be pursued through phase III trials in 2024.”

Emmanuel de Rivoire, Chief Executive Officer of Kinnov Therapeutics, adds: "The completion of the Phase II study with KT-110, our lead drug candidate, is a major milestone for Kinnov. Alcohol dependence, or AUD, is a serious public health issue and the medical need for the treatment of alcoholism is considerable and unmet: no new drug has been brought to market since 2013. Alcoholism is a crippling disease that is prohibitively expensive to treat and causes three million deaths every year.

“With KT-110, we hope to make a real difference in the care and quality of life of patients suffering from the severe consequences of alcoholism. Armed with these promising results, we are now seeking a commercial pharmaceutical partner to continue the development and commercialisation of KT110 and enable patients to gain access to this innovative treatment.”

Kinnov Therapeutics expects to have clear guidance from the FDA in 2024 on the phase III trial.