Sprout Pharmaceuticals
Addyi (flibanserin), a drug dubbed the ‘female Viagra’, has been approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women by the US Food and Drug Administration (FDA).
Women with HSDD have low sexual desire that causes distress or interpersonal difficulty and is not caused by a co-existing medical or psychiatric condition, problems within a relationship, or the effects of a drug.
Flibanserin, a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, is the first drug to be approved for the treatment of this disorder, although the mechanism by which it improves sexual desire and related distress is unclear.
The drug has previously been rejected twice by the FDA, which led to accusations of gender bias.
Even the Score, a women’s sexual health advocacy group, says around one in ten women have HSDD. It has campaigned for treatments such as flibanserin to be approved and says that while the FDA decision is “a tremendous step in the right direction, the score is hardly even”.
“With 26 FDA-approved treatment options for men’s sexual dysfunction and only one for women, we have a long way to go in recognising the important role sexual desire plays in a woman’s overall health,” says Even the Score.
Women taking flibanserin to improve sexual desire will have to refrain from drinking alcohol and stop taking several common drugs, including certain antidepressants, antibiotics, antifungals, reflux treatments and protease inhibitors.
Flibanserin can cause severely low blood pressure (hypotension) and loss of consciousness (syncope) and these risks are increased when patients drink alcohol, take drugs that are CYP3A4 inhibitors, or have liver impairment. Patients should not drive for at least six hours after taking Addyi.These risks are highlighted in a boxed warning.
As a patient’s likelihood of abstaining from alcohol must be assessed reliably, flibanserin has been approved with a risk evaluation and mitigation strategy (REMS). This means it must be prescribed and dispensed by certified doctors and pharmacists, who will have undergone specific training.
Certified prescribers must use a patient-provider agreement form and counsel patients about the increased risk of severe hypotension and syncope and about the importance of not drinking alcohol when taking the drug. Certified pharmacies must only dispense flibanserin to patients with a prescription from a certified prescriber, and must remind patients prior to dispensing the drug not to drink alcohol during treatment.
The effectiveness of a 100mg bedtime dose of flibanserin was evaluated in three 24-week randomised, double-blind, placebo-controlled phase III trials in around 2,400 premenopausal women who had experienced acquired, generalised HSDD for an average of five years. Compared with placebo, around 10% more Addyi-treated patients reported meaningful improvements in satisfying sexual events, sexual desire or distress. The most common adverse reactions were dizziness, somnolence (sleepiness), nausea, fatigue, insomnia and dry mouth.
The FDA has told Sprout Pharmaceuticals, which markets Addyi, that it must conduct a further three studies to better understand the risks of the interaction between Addyi and alcohol.
Sprout Pharmaceuticals has not yet made an application for a marketing authorisation to the European Medicines Agency.
Flibanserin was developed by Boehringer Ingelheim but, after the FDA rejected it in 2010, Boehringer ceased development of the drug and the rights were transferred to Sprout Pharmaceuticals.
On 20 August 2015, two days after the FDA approved flibanserin, Valeant Pharmaceuticals announced it was to acquire Sprout Pharmaceuticals, subject to regulatory approval, for US$1bn in cash. The deal also includes a share of future profits of flibanserin, which has the potential to be a blockbuster drug if it achieves the same level of use in women as Viagra and other erectile dysfunction drugs have had in men. Valeant’s scale and resources will make it easier to seek approval and sales of flibanserin in Europe and other markets outside the United States.
Edward Morris, a consultant gynaecologist and a spokesperson for the Royal College of Obstetrics and Gynaecology, says: “Some drugs, which are licensed for other conditions, may be helpful in carefully selected women, such as testosterone gels for post-menopausal women, or for women who have had their ovaries removed, drugs such as bupropion and tibolone.
“Whilst it is welcome that research in this area continues to improve and that there is potential for a new drug for women with HSDD, we must not forget that, as is the case with flibanserin, all of these medications have side effects,” he adds.
