Orenetide for the treatment of hypoactive sexual desire disorder: results of a randomized placebo-controlled trial


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Abstract

Hypoactive desire disorder (HSDD) is characterized by a distressing and prolonged deficiency of sexual desire. Currently, despite the high prevalence of HSDD in women, the potential of drug treatment for this problem is limited: there are only two pharmacologic treatments both with modest efficacy, approved in a limited number of countries. Desirix (INN Orenetide) - is an innovative peptide drug developed in Russia to restore sexual desire and concomitant functions in women with HSDD. Aim: This study aimed to conf irm the safety and eff icacy of Desirix (INN Orenetide) in premenopausal women with HSDD. Materials and methods: This randomized, double-blinded, placebo-controlled, multicenter, 12-week Phase III clinical trial in parallel arms was conducted at 19 sites within the Russian Federation (Russian CTA #688 dated 25.12.2017; ClinicalTrials.gov NCT03463707). The study enrolled 189 premenopausal women with diagnosed Lack or loss of sexual desire (ICD-10 code F52.0; equivalent to acquired generalized HSDD according to DSM-IV), aged 21-50 years. Participants were eligible if they had a regular menstrual cycle and low sexual desire for at least 24 weeks prior to screening. After 4 weeks of baseline assessment (screening period) participants were randomly assigned to receive Desirix (Orenetide, development code BP101) 2 mg/day nasal spray or identical placebo. 95/189 (50,3%) participants were randomized to Desirix (Orenetide) treatment arm, and 94/189 (49,7%) to placebo arm. After 4-weeks daily treatment period there was 8-weeks no-treatment follow-up. The primary efficacy outcome was the change in number of satisfying sexual events (SSEs) after 4 weeks of therapy compared to a baseline period. Secondary efficacy outcomes included changes in the number of SSEs in the follow-up period; changes in the number of sexual events leading to orgasm, total Female Sexual Function Index (FSFI) score, FSFI “desire” domain, total Female Sexual Distress Scale-Revised (FSDS-R) score, FSDS Item 13 (“[How often... you were] Bothered by low sexual desire?”) score and assessment of Patient Global Impression of Improvement, PGI-I) after treatment, and after 4 and 8 weeks of follow-up. The incidence and nature of adverse events (AEs) was recorded. Results: The primary efficacy endpoint was met as Desirix (Orenetide) had a higher mean change in the number of SSEs after 4 weeks of treatment with the mean treatment difference of 1,83 (95,9% CI: 0,28-3,39; р=0,02) compared to placebo. Desirix (Orenetide) significantly increased SSEs compared to placebo at the 4-week - 2,38 (95% CI: 0,62-4,13;р<0,01) and 8week - 2,37(95% CI: 0,70-4,05;р<0,01) follow-up visits. Greater changes in total FSFI score and for “desire”, “arousal” and “orgasm” domains, as well as PGI-I score were reported at all time-points in the Desirix (Orenetide) treatment arm (p<0,05 vs placebo). Desirix (Orenetide) effectively reduced the signs of distress on the FSDS-R scale, and increased in the mean number of sexual events leading to orgasm at 4 weeks of treatment and at 8 weeks of follow-up (p<0.05 vs placebo). Most AEs were mild, caused no trial discontinuations and no serious treatment-related AEs were reported. Conclusion: Desirix (Orenetide) medicine is an efficacious and safe treatment for HSDD in premenopausal women.

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About the authors

Gennadiy T. Sukhikh

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Academician of the RAS, Dr. Med. Sci., Professor, Director

Anatoliy B. Smulevich

Psychiatric Hospital No. 1 named after N.A. Alexeev, Department of Health of Moscow

Academician of the RAS, Dr. Med. Sci., Professor, Head of the Department for the Study of Borderline Mental Pathology and Psychosomatic Disorders, MHRC

Natalia N. Stenyaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

PhD, Senior Researcher

Daniil G. Nemenov

IVIX Ltd

M.D., Chief executive officer

Vera N. Prilepskaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Dr. Med. Sci., Professor, Head of the Scientific Polyclinic Department

Dmitriy F. Khritinin

I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University)

Corresponding Member of the RAS, Dr. Med. Sci., Professor at the Department of Psychiatry and Narcology of the NV. Sklifosovsky Institute of Clinical Medicine

Nikolay F. Myasoedov

Institute of Molecular Genetics of National Research Centre «Kurchatov Institute»

Academician of the RAS, Dr. Chem. Sci., Professor, Head of the Laboratory of Molecular Pharmacology of Peptides

Aleksey A. Matskevich

IVIX Ltd

PhD (Bio), Chief Researcher

Lyudmila A. Andreeva

Institute of Molecular Genetics of National Research Centre «Kurchatov Institute»

Deputy Head of the Laboratory of Molecular Pharmacology of Peptides, Head of the Regulatory Peptides Sector of the Physiologically Active Substances Chemistry Department

Elena V. Zelenina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

PhD, psychiatrist

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