fter a two-year wait, the US Food and Drug Administration finally issued new guidance for companies that want to develop drugs to bolster female libidos. But the details suggest the agency has belatedly learned some hard-fought lessons following complaints that the controversial Addyi pill did not warrant approval last year.
The 15-page draft guidance, which was released Tuesday, offers a typical how-to for companies, but also points to certain steps that Sprout Pharmaceuticals did not follow as part of its Addyi marketing application to the FDA. The drug, which is now sold by Valeant Pharmaceuticals, was approved despite debate over its safety and effectiveness, and the extent to which medicines should be used to treat female sexual dysfunction.
It “looks like the FDA is using this guidance to keep another company from trying to get a female sexual desire drug approved based on unreliable data collection instruments and weak results,” said Cindy Pearson, executive director of the National Women’s Health Network, who opposed the approval. “Unfortunately, the FDA is locking the barn door after the horse got out. So now, the agency is telling other companies to do some things that Sprout didn’t do.”
Sprout won approval for Addyi, which has been a poor seller, after an unusual campaign that accused the FDA of bias. Along with other drug makers and some consumer advocacy groups, the company alleged the agency failed to approve medications to combat female sexual problems while arguing that nearly two dozen such treatments exist for men. The FDA refuted the charges and noted the tally incorrectly included some drugs.
Nonetheless, the campaign won backing from some congressional lawmakers, and two years ago, the FDA held a workshop to gather information for developing its guidance. Meanwhile, the agency last year approved the drug, even though critics maintained the FDA was lowering approval standards because some of the clinical trial information submitted by Sprout was insufficient. The FDA later rejected the criticism.
Going forward, for instance, the FDA wants companies to limit so-called exclusion criteria. Drug makers may exclude certain patients from a clinical trial for legitimate reasons, but may also do so in a way that can benefit the outcome. Pearson noted that Sprout had set a great deal of exclusion criteria for determining clinical trial eligibility.
The agency also wants drug makers to use a validated tool to gauge patient reactions to a tested medicine. Sprout used, although the FDA did not rely entirely on, something called the Female Sexual Function Index to measure desire and arousal. The FDA guidance notes that the agency is “unaware of data that adequately establish the validity of the instrument as a whole for regulatory purposes.”
What else? The FDA would also like shorter recall periods — ideally, daily or weekly — for patient reports, instead of the 28-day recall period used by Sprout. However, companies can use longer recall periods and compare that with a shorter period, which Sprout did. And the agency would like information about women who are pre- and post-menopausal, since such a medicine may interest women of all ages, but Sprout only included trial data on pre-menopausal women. Addyi was only approved for pre-menopausal women, by the way.
“On balance, I think they’ve made it harder to get a drug approved but they have extended helping hands in numerous places,” said Leonore Tiefer, a clinical associated professor in psychiatry at the New York University School of Medicine, who has been critical of efforts to label female sexual dysfunction as a genuine disorder.
“In my opinion, unless [a company] really looks hard for subgroups [of patients], the whole effort is hopeless. Some women can be found that can benefit using these instruments and endpoints, but there aren’t very many,” Tiefer said. “Most [companies] want big markets, and they won’t be able to get a drug through that can help most women with desire and arousal complaints because those complaints are due to nonmedical factors.”
This post was updated to clarify that the FDA guidance indicates companies can use longer recall periods and compare that with a shorter period, and that Sprout did so.