Products

TGFK09SD
Therapeutic Area(s): Hypoactive Sexual Desire Disorder

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

Pharmacology
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. TGFK09SD is a 5HT1a agonist.

Clinical Trials
Various data measuring sexual function was collected in 5 Phase III studies of TGFK09SD-ER 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 Forth Edition (DSM-IV) includes HSDD as an official psychiatric diagnosis. In three TGFK09SD 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 TGFK09SD 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 TGFK09SD-ER 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 TGFK09SD-ER 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 TGFK09SD-ER doses were acceptable with the main adverse events confined to mild nausea and dizziness

Pre-IND FDA meeting
The FDA has assigned IND number 104,950 for TGFK09SD-ER 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 TGFK09SD-ER for this indication. Issues to be discussed include:

1. The overall safety of TGFK09SD-ER 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
There are no drugs currently approved to treat Female HSDD. 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.

Conclusions
TGFK09SD-ER 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 TGFK09SD-ER should be the first of a new class of medications to treat this problem.

Partners
Development and marketing partnerships are available.