The science behind Lybrido

Previous attempts to develop a drug treatment for FSIAD have fallen into the “one size fits all” approach,
while failing to acknowledge the complexity of female sexuality.

Freya’s solutions are based on known neurobiological mechanisms that are important in sexual excitation and inhibition in women.

Lybrido focuses on treatment for patients with FSIAD, in which low sexual desire or arousal results from a central nervous system that is relatively insensitive to sexual cues. In these individuals, exposure to sexual stimuli (internal or external) fails to trigger activation of the brain’s sexual excitatory mechanisms.

(Bloemers et al. 2013, van der Made et al. 2009, Poels et al. 2013, van Rooij et al. 2013)


two horizontal bars showing that lybrido and lybridos have both completed phase 2 of clinical trials

Lybrido

Lybrido has been developed for patients with FSIAD, who are relatively insensitive to sexual cues. It increases central sexual motivation and physiological sexual responses, such as swelling of vaginal erectile tissue and lubrication. Lybrido contains sildenafil (a phosphodiesterase type 5 inhibitor) with a time-release coating and an outer testosterone shell.

A Phase 3 trial for Lybrido is currently in preparation, and is expected to run from late 2022 until mid-2024.

Three phase 2 studies (two for Lybridos and one for Lybrido) have been conducted at 16 research sites in the United States. The efficacy and safety of various doses of testosterone, sildenafil, buspirone and combination therapies (testosterone + sildenafil, testosterone + buspirone) were tested in 497 women with FSIAD to determine the change in satisfying sexual events (SSEs) over a period of eight weeks.

In women with low sensitivity for sexual cues (Lybrido group), 0.5 mg testosterone + 50 mg sildenafil increased the number of SSEs by 170% compared with placebo, by 195% compared with sildenafil alone, and by 169% compared with testosterone alone.

In women with overactive inhibition (Lybridos group), 0.5 mg testosterone + 10 mg buspirone increased the number of SSEs by 99% compared with placebo, by 152% compared with buspirone alone, and by 98% compared with testosterone alone.

For further details on the clinical studies, see the Key Publication below.

The pill is placed under the tongue for about 90 seconds, and then the remainder of the pill can be swallowed.

The reason for this two-way administration is so that the testosterone coating of the pill can be absorbed directly into the bloodstream via the blood vessels under the tongue, while the pill core dissolves slowly in the GI tract so that the sildenafil is released a few hours later.

Lybrido is designed to be taken only when desired – it is not necessary to take it daily.

Sexual motivation is increased between 3 to 6 hours after intake.

Lybrido is composed of a testosterone outer coating combined with a core of time-delayed sildenafil, which increases blood flow to the genitals.


Testosterone

Testosterone makes the brain more responsive to sexual cues, which in turn increases sexual motivation. A single dose of 0.5 mg testosterone under the tongue produces a brief increase in the blood plasma level of testosterone within 15 minutes, which returns to normal levels within 2 to 3 hours. During a period of 3 to 6 hours after peak plasma levels, there will be an increase in vaginal arousal and subjective sexual responses.

The peak in testosterone in Lybrido mimics the natural peak that occurs in women during ovulation, the phase of the menstrual cycle in which women typically experience increased sexual motivation and desire.


Sildenafil

The inner-core of Lybrido contains 50mg of sildenafil, which increases blood flow to the genitals. The increase in sexual motivation caused by the testosterone is required for its activation.

The sildenafil is coated with a time-delay substance to ensure that its release into the bloodstream occurs at the same time as the window of increased sexual motivation induced by the testosterone. This combination increases genital arousal by increasing responsiveness to sexual stimuli.

Tuiten A et al. Efficacy and safety of on-demand use of two treatments designed for different etiologies of Female Sexual Interest/Arousal Disorder: Three randomized clinical trials. J Sex Med, 2018; 15: 201-216. https://www.jsm.jsexmed.org/article/S1743-6095(17)31851-9/fulltext

2020

Gerritsen J et al. The effect of food on the pharmacokinetics of buspirone after single administration of a sublingual testosterone and oral buspirone combination tablet in healthy female subjects. Sex Med 2020 Jun; 8(2): 186-194. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261678/

2019

Bloemers J et al.The effect of food on the pharmacokinetics of sildenafil after single administration of a sublingual testosterone and oral sildenafil combination tablet in healthy female subjects. J Sex Med 2019; 16: 1433-1443. https://www.jsm.jsexmed.org/article/S1743-6095(19)31274-3/fulltext

2018

Tuiten A et al. Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial. Women’s Health, July 2018; 14. http://journals.sagepub.com/doi/full/10.1177/1745506518788970#articleShareContainer

Van Nes Y et al. Psychometric properties of the Sexual Event Diary in a sample of Dutch women with Female Sexual Interest /Arousal Disorder. J Sex Med, 2018; 15: 722-731. https://pubmed.ncbi.nlm.nih.gov/29699757/ 

2017 

Van Nes Y et al. The Sexual Event Diary (SED): development and validation of a standardized questionnaire for assessing female sexual functioning over discrete sexual events. J Sex Med, 2017; 14: 1438-1450. https://pubmed.ncbi.nlm.nih.gov/28993148/ 

2016

Bloemers J et al. Single dose sublingual testosterone and oral sildenafil versus a dual-route/dual-release fixed-dose combination tablet: a pharmacokinetic comparison. BJ Clin Pharm, 2016;81:1091-1102. https://pubmed.ncbi.nlm.nih.gov/26804967/ 

2015

Suschinsky KD et al. The Clitoral Photoplethysmograph: A Pilot Study Examining Discriminant and Convergent Validity. Sex Med. 2015 Dec;12(12):2324-38. https://pubmed.ncbi.nlm.nih.gov/26632084/

2014

van Rooij K et al. Efficacy of testosterone combined with a PDE5 inhibitor and testosterone combined with a serotonin 1A receptor agonist in women with SSRI-induced sexual dysfunction. Eur J Pharmacol, 2014. https://www.sciencedirect.com/science/article/abs/pii/S0014299914007973

van Rooij K et al. Pharmacokinetics of a prototype formulation of sublingual testosterone and a buspirone tablet, versus an advanced combination tablet of testosterone and buspirone in healthy premenopausal women. Drugs in R&D, 2014; 14: 125-32. https://pubmed.ncbi.nlm.nih.gov/24849043/

Poels S et al. Two novel combined drug treatments for women with Hypoactive Sexual Desire Disorder. Pharmacology, Biochemistry and Behavior, 2014; 121: 71-79. https://www.sciencedirect.com/science/article/abs/pii/S0091305714000318?via%3Dihub

2013

Bloemers J et al. Toward Personalized Sexual Medicine (Part 1): Integrating the “Dual Control Model” into Differential Drug Treatments for HSDD and FSAD. Journal of Sexual Medicine 2013; 10(3): 791-809. https://www.jsm.jsexmed.org/article/S1743-6095(15)30308-8/fulltext

Poels S et al. Toward Personalized Sexual Medicine (Part 2): Testosterone combined with a PDE5 inhibitor increases sexual satisfaction in women with HSDD and FSAD, and a low sensitive system for sexual cues. Journal of Sexual Medicine 2013;10 (3): 810-823. https://pubmed.ncbi.nlm.nih.gov/23130748/

van Rooij K et al. Toward Personalized Sexual Medicine (Part 3): Testosterone combined with a serotonin1A receptor agonist increases  sexual satisfaction in women with HSDD and FSAD, and dysfunctional activation of sexual inhibitory mechanisms. Journal of Sexual Medicine 2013; 10(3): 824-837. https://pubmed.ncbi.nlm.nih.gov/23130675/

2012

van Rooij K et al. Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women. Psychoneuroendocrinology 2012; 37(6): 773-81. https://pubmed.ncbi.nlm.nih.gov/21982723/

2009

van der Made F et al. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. Journal of Sexual Medicine 2009; 6(3): 777-90. https://pubmed.ncbi.nlm.nih.gov/19207276/

2002

Tuiten A et al. Can sublingual testosterone increase subjective and physiological measures of laboratory-induced sexual arousal? Archives of General Psychiatry, 2002; 59: 465–466. https://pubmed.ncbi.nlm.nih.gov/11982451/

2000

Tuiten A et al. Time course of effects of testosterone administration on sexual arousal in women. Archives of General Psychiatry 2000; 57(2): 149-53. https://pubmed.ncbi.nlm.nih.gov/10665617/

Contact us for more information

Freya Pharma Solutions B.V.
Kraanspoor 50 | 1033 SE Amsterdam | The Netherlands

info@freyapharmasolutions.com 

© Freya Pharma Solutions. All rights reserved.
Contact us for more information

Freya Pharma Solutions B.V.
B.V. Kraanspoor 50 | 1033 SE Amsterdam | The Netherlands

info@freyapharmasolutions.com

© Freya Pharma Solutions.
All rights reserved.