Nastech reports positive FSD results

Nastech Pharmaceutical has reported positive results from a Phase II At-Home clinical trial using its investigative intranasal formulation of apomorphine to treat female sexual dysfunction (FSD).

FSD is defined as persistent or recurring reduction of sex drive or aversion to sexual activity, difficulty becoming aroused, inability to reach orgasm, and pain during sexual intercourse.

'Our experience with intranasal apomorphine in this Phase II study in women is very positive,' said Barbara Troupin, M.D., lead investigator at Radiant Research in San Diego, California. 'Patients are very excited about this product, viewing it as an appealing potential therapy for the treatment of FSD. The results of this study clearly support further clinical development.'

Initial efficacy results were reported in data from 38 women enrolled in the study. All the patients enrolled in the study were pre-menopausal and had been diagnosed with Female Sexual Arousal Disorder (FASD). The prospectively designed study was based on data both in a contemporaneous event log as well as a four-week 'look back' format.

95% of the women also had a diagnosis of acquired hypoactive sexual desire disorder (HSDD). In addition, nearly half the patients enrolled in the study had free testosterone plasma concentration of less than 0.9 pg/mL, which has been associated with a decrease in sexual function. Both HSDD and low testosterone have been used as exclusion criteria in other studies of female sexual dysfunction because patients with these conditions have shown the poorest treatment effects with other investigational drugs. For example, a recent study of sildenafil in the treatment of FSD failed to show efficacy in women with HSDD even though low testosterone was an exclusion criteria for entrance in the study.

   Results reported from the study show that in women taking 0.5 mg intranasal apomorphine, 23 parameters studied showed a statistically significant improvement from baseline, including sexual relationship satisfaction (p=0.01), overall sexual life satisfaction (p=0.0007), arousal frequency (p=0.003), arousal intensity (p=0.008), arousal satisfaction (p=0.001), confidence in becoming aroused (p=0.02), maintaining the aroused state (p=0.0001), frequency of adequate lubrication (p=0.0003), overcoming difficulty becoming lubricated (p=0.003), orgasmic quality (p=0.003), orgasmic frequency (p=0.01), orgasmic satisfaction (p=0.01), and overcoming difficulty in achieving orgasm (p=0.006).

With respect to the five domain score results, apomorphine produced improvements from baseline in satisfaction (p=0.002), orgasm (p=0.004), lubrication (p=0.003), desire (p=0.01), arousal (p=0.004) and total domain scores (p=0.0007). However, due to the small number of patients enrolled in the study, the difference between apomorphine and placebo treatments did not reach statistical significance.

In the primary efficacy endpoint of the study, improvement in satisfaction with sexual activity, 55% of women responded in the affirmative after taking intranasal apomorphine compared with 31% prior to the study.

Adverse events in both apomorphine and placebo groups were generally mild, and all were resolved without intervention. There were no serious adverse events reported in the study, there was one headache (3%) and no observations of flushing, nausea, vomiting, hypotension, or syncope. A recent study of sildenafil in women with FSD had an adverse event frequency of headache (33%), flushing (23%), nausea (7%), and abnormal vision (6%) among women who completed the study (11% dropped out of the study before completion).

   'More than 50m American women suffer from sexual dysfunction,' stated Steven C. Quay, md chairman, president, and ceo of Nastech. 'Many of these women do not seek evaluation and treatment because of self-imposed inhibitions. The results of our Phase II study suggest that nasal apomorphine may play a significant role in correcting hypoactive sexual desire because of its novel pharmacological action in brain centres involved with normal sexual physiology and supports our decision to continue clinical efficacy studies in women. Based on the effects seen in this study, a larger number of patients would be expected to show robust, statistically significant efficacy on parameters considered important for regulatory approval of drugs in this class.'

Apomorphine

Apomorphine is a potent dopamine agonist that promotes sexual function by stimulating the D1/D2 class of dopamine receptors in the brain. Nastech's proprietary nasal formulation is designed to maximise the rapid onset, therapeutic effect and overall safety of apomorphine.

Female sexual dysfunction

According to a published survey in The Journal of the American Medical Association, four in ten American women experience some form of sexual dysfunction, a figure likely to increase as the 41m 'baby boomer' women age. Female sexual dysfunction (FSD) currently consists of four recognized components: decreased sexual desire, decreased sexual arousal, dyspareunia (painful sexual intercourse) and persistent difficulty in achieving orgasm. The causes of FSD are complicated and may include psychological problems such as depression, stress and fatigue. The intranasal apomorphine formulation under development is targeted to act on receptors in the central nervous system that may improve sexual arousal and dyspareunia.