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FDA Advisory Committees Recommend Approval of Flibanserin (Addyi) to Treat Sexual Desire Disorder in Women
In a joint meeting, the FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee, and the Drug Safety and Risk Management Advisory Committee have determined by an 18-to-6 vote that the benefit–risk profile of flibanserin (Addyi, Sprout Pharmaceuticals) supports FDA approval of the drug for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, but only if certain risk-management options beyond labeling are implemented.
HSDD is the most common form of female sexual dysfunction. The condition is characterized by a deficiency or absence of sexual fantasies and of the desire for sexual activity, which causes marked distress or interpersonal difficulty, and is not better accounted for by another disorder or by the effects of a substance. HSDD does not encompass normal (e.g., daily or weekly) fluctuations in levels of desire. Approximately one in three women in the U.S. have low sexual desire, and one in 10 women (16 million women total) are distressed by it.
Flibanserin is a multifunctional serotonin agonist antagonist (MSAA) and, if approved, would be the first postsynaptic 5-hydroxytryptamine 1A (5-HT1A) receptor agonist and 5-HT2A receptor antagonist available to prescribers for the treatment of premenopausal women with HSDD.
It is believed that flibanserin helps restore prefrontal cortex control over the brain’s motivation and rewards structures, enabling sexual desire to manifest. This is thought to be accomplished by the rebalancing of neurotransmitters that influence sexual desire. Specifically, flibanserin increases dopamine and norepinephrine (both responsible for sexual excitement) while transiently decreasing serotonin (responsible for sexual satiety or inhibition) in the brain’s prefrontal cortex. This is likely accomplished by reduced glutamate transmission.
In clinical studies, flibanserin was evaluated for its ability to increase the frequency of satisfying sexual events, to increase the intensity of sexual desire, and to decrease the associated distress women feel from its loss.
In three 24-week, phase III, randomized, double-blind, placebo-controlled, parallel-group North American studies of premenopausal women (mean age: 36 years), flibanserin demonstrated a statistically significant difference compared with placebo on three key endpoints: an increase in sexual desire, a decrease in distress from the loss of sexual desire, and an increase in the frequency of satisfying sex. Improvements in all three parameters were observed within 6 months in 43% to 60% of the subjects.
The safety of flibanserin was evaluated in more than 8,500 women, of whom more than 1,000 were exposed to treatment for at least 1 year. The most common adverse events were dizziness, nausea, and sleepiness.
Source: Sprout Pharmaceuticals; June 5, 2015.