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EXXUA™ for Hypoactive Sexual Desire Disorder

Therapeutic Area: Hypoactive Sexual Desire Disorder
Phase of Development: Phase II

Development Status:
Proof of concept was confirmed in several antidepressant studies which showed improved sexual functioning. CMC and two-year carcinogenicity studies complete.

There are no credible animal models for HSDD. However, there is evidence that 5HT1A agonists are effective in the treatment of HSDD. An example is the Rose Study of Flibanserin in HSDD conducted by Boehringer-Ingelheim. EXXUA is a 5HT1A agonist.

Clinical Trials
Various data measuring sexual function was collected in 5 Phase III studies of EXXUA in MDD in accordance with study protocols. Effect on sexual function was a stated protocol objective in 3 of these studies; 134004, 134006, and 134017. The central issues in the diagnosis of HSDD are low sexual desire coupled with distress or interpersonal difficulty. The Diagnostic and Statistical Manual Fifth Edition (DSM-V) includes HSDD as an official psychiatric diagnosis. In three EXXUA studies, female patients were examined at each visit to determine whether or not they met criteria for HSDD. Of interest are those who met diagnostic criteria but later with treatment did not. These patients who resolved their HSDD diagnosis were more prevalent in EXXUA treated subjects than placebo treated and the effect was statistically significant in one study 134006 (p=.03). The DISF desire domain which measures a similar sexual deficit found the same results. For the three studies combined, the results on the DISF desire domain were statistically significantly increased at week 8 endpoint (p=0.001) and as early as week 2 (p=0.001).

While none of the EXXUA studies measured changes in numbers of sexual events or other patient reported outcomes (PROs) that are the currently preferred measures of efficacy provided by the FDA Division of Reproductive and Urologic Products (DRUP), Fabre-Kramer and our outside consultants believe that the demonstrated effects utilizing the measures employed in these studies are reasonably predictive of similar results in future studies utilizing DRUP preferred measures.

The dose of EXXUA taken when statistically significant improvement in HSDD occurred was 40-60 mg/day. Whether or not lower doses would be effective remain for future investigation. Adverse events and safety measures at these EXXUA doses were acceptable with the main adverse events confined to mild nausea and dizziness

Pre-IND FDA Meeting
The FDA has assigned IND 104,950 for EXXUA in the treatment of HSDD. A meeting has been set to discuss the data currently available and to agree on a program to gain FDA approval of EXXUA for this indication. Issues to be discussed include:
1. The overall safety of EXXUA warrants study in an HSDD population
2. No new clinical pharmacology studies are required
3. No new pharmacology or toxicology studies are required
4. No pediatric studies are required. Drug inappropriate for pediatrics
5. Cardiovascular safety is established and there are no QTc issues
6. Initial dosing of 40-60 mg/day is acceptable
7. A phase II protocol with endpoints at 24 weeks of increase in number of satisfying sexual events and decrease in stress is adequate

HSDD Market
In a 1999 AMA survey, 43% of women over 20 reported sexual dysfunction. The sexual dysfunction in women occurred at all ages, with the majority over 50. After menopause, with the loss of female hormones, sexual drive diminishes greatly.

Attempts to treat HSDD to date have largely focused on manipulation of sexual hormones. For example, small amounts of testosterone increase sexual desire in females. However, FDA has been cautious in approving drugs utilizing this approach, due to possible cancer and cardiovascular risk.

It has been estimated that the HSDD Market may be as large as the Erectile Dysfunction Market.

EXXUA is a safe drug which has met all FDA safety requirements. The remaining issues for an NDA for HSDD can be accomplished in 2-3 years. The cost is relatively low, a fraction of the cost for an NCE. The market is large and EXXUA should be the first of a new class of medications to treat this problem.

Development and commercialization partnering opportunities are available.