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Hypoactive sexual desire disorder (HSDD) affects 10% of women in the United States1 and significantly higher percentages of women who have undergone surgical menopause.2 People are diagnosed with this condition if they experience low or no desire for sex together with significant distress or interpersonal difficulties due to this lack of desire. HSDD can have a serious effect on emotional well-being and interpersonal relationships and it occurs in pre- and postmenopausal women.

There are no U.S. Food and Drug Administration-approved treatments for this large, unmet medical need. Off-label treatments include testosterone, which is not always effective and can be accompanied by side effects such as excess hair growth, acne, and decreases in high-density lipoprotein (HDL) cholesterol levels.3 In 2006, the Endocrine Society concluded that although there is evidence for short-term efficacy of testosterone in some populations, generalized use of testosterone by women is not recommended because of poorly defined indications for treatment and the lack of long-term studies of safety.4

Research in laboratory animals and clinical observations in humans have suggested that modulating the balance of neurotransmitters by increasing dopaminergic activity and decreasing serotoninergic activity may stimulate sexual desire.5 S1 Biopharma’s lead product, Lorexys, is a novel use fixed-dose combination (FDC) in oral enteric formulation acting on the central nervous system. The drug is a combination of two antidepressants that work synergistically to restore homeostasis to the brain’s mechanisms controlling sexual function. One component increases norepinephrine; the other inhibits serotonin type 2A receptors. Both such effects are known to be prosexual in clinical studies for other indications and are expected to have similar effects in women with HSDD.6 Each agent has other receptor targets too, and these may play a significant role in their synergistic prosexual effects.

The compound showed marked prosexual effects without any side effects in a single-case study and is Phase 2-ready because of the known safety of co-prescribing the two agents to depressed patients. The Phase 2 clinical trial can proceed rapidly and with confidence in the measures of efficacy (compared to prior development efforts in this field) because treatment-sensitive endpoints (such as the Female Sexual Function Index and the Female Sexual Distress Scale — Revised) are now well-validated and publicly available.

S1 Biopharma is also developing a treatment for HSDD in men. HSDD can be diagnosed in men without erectile dysfunction.7 Although PDE5 inhibitors such as Viagra can address the physical condition, they do not relieve HSDD. The second program in S1 Biopharma’s pipeline, S1P-205, is targeting HSDD in men and is being readied for Phase 1b/2a trials. When men develop HSDD, the rest of their sexual function may also deteriorate.8,9 Fortunately, broad-spectrum efficacy not only for sexual desire but also for arousal, orgasm, and satisfaction is suggested for S1P-205 by an N-of-1 male study (data on file, S1 Biopharma, 2012).

There is growing awareness of the prevalence of HSDD and related sexual disorders, leading to an appreciation of the degree of unmet medical need in this area. If Lorexys performs as expected in upcoming clinical trials, physicians can begin to address this need with a new class of drug, potentially leading to a significant improvement in the quality of life for their HSDD patients.

References
1. Shifren JL, et al. Sexual Problems and Distress in United States Women: Prevalence and Correlates. Obstetrics & Gynecology. 2008; 112(5):970-978.
2. Leiblum SR, et al. Hypoactive sexual desire disorder in postmenopausal women: US results from the Women's International Study of Health and Sexuality (WISHeS). Menopause. 2006;13(1):46-56.
3. Rossella EN, et al. Management of hypoactive sexual desire disorder in women: current and emerging therapies. Int J Womens Health. 2010; 2: 167–175.
4. Woodis CB, et al. Testosterone Supplementation for Hypoactive Sexual Desire Disorder in Women. Pharmacotherapy. 2012; 32(1):38-53.
5. Pfaus JG. Pathways of sexual desire. J Sex Med. 2009; 6(6):1506–1533.
6. Data on file, S1 Biopharma.
7. DeRogatis L, et al. Characterization of hypoactive sexual desire disorder (HSDD) in men. J Sex Med. 2012; 9(3):812-20.
8. Corona G, et al. The impotent couple: low desire. 2005; 28(Suppl 2):46-52.
9. Fugl-Meyer AR. Sexual disabilities are not singularities. Int J Impotence Res. 2002;14:487-493.

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