Posted 25 October 2016
By Zachary Brennan
The controversial US Food and Drug Administration (FDA) approval last year of the first drug intended to treat women bothered by a lower sex drive has opened the door for other companies to develop similar drugs.
Now, FDA is trying to clarify what these drug developers racing to create the next female Viagra should focus on, with particular discussion of the challenges involved, including diagnostic criteria, endpoints and patient-reported outcome (PRO) instruments.
The release of the draft guidance on Tuesday comes as the first drug to treat a form of female sexual dysfunction – Sprout’s Addyi (flibanserin), which was later acquired by the infamous Valeant Pharmaceuticals for $1 billion but quickly turned into a commercial flop – raised questions about FDA’s use of subjective patient input in an approval, companies lobbying the agency and what constitutes a distressingly low sex drive and subsequent improvement.
For instance, was Addyi a market failure because it didn’t work well (the drug was previously rejected twice and women in trials reported about one more sexually satisfying experience per month than those on placebo) or because of the difficulty in trying to decipher the cause and pathway to treat what FDA calls, “low sexual interest, desire, and/or arousal that cause marked distress or interpersonal difficulty in women, including female sexual interest/arousal disorder (FSIAD), hypoactive sexual desire disorder (HSDD), and female sexual arousal disorder (FSAD)”?
Drug Development Guidance
In trying to help companies develop such treatments, the agency makes clear up front in its 12-page draft guidance that the symptoms of these aforementioned conditions are not considered to be caused by: a coexisting medical or psychiatric condition, problems within a relationship or the effects of a medication or other drug substance.
FDA also makes clear that there are fundamental problems associated with trying to develop such treatments.
For example, diagnostic criteria for disorders of low sexual interest, desire, and/or arousal in women were recently revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, but FDA notes that these “revisions have not been universally accepted by the scientific community.”
In addition, in the draft guidance’s section on clinical outcome assessment instruments, FDA points out the Female Sexual Function Index (FSFI), a 19-item list used in clinical trials to measure overall sexual function, and how it may not actually be accurate. FDA says it’s “unaware of data that adequately establish the validity of the instrument as a whole for regulatory purposes.”
The agency also notes that if one component (e.g., sexual fantasies) of this FSFI list is increased with an experimental drug, but other components (e.g., wanting, initiating or feeling receptive to sexual activity) have not improved, “A score change suggesting improvement could be shown; however, it is unclear whether this represents a meaningful benefit to patients.”
However, despite these limitations, FDA says one part of another scale, Question 13 of the Female Sexual Distress Scale-Revised (FSDS-R) instrument, is considered acceptable for measuring a woman’s distress related to decreased sexual desire.
“This question asks ‘How often did you feel: Bothered by low sexual desire?’ Subjects assess their sexual distress over a 7-day recall period and respond on a scale of 0 (never) to 4 (always),” the draft says.
FDA also makes clear that Phase 2 studies offer an opportunity to evaluate measurement properties of PRO instruments and can inform instrument design and the adequacy for use in the Phase 3 trials.
“We strongly recommend that sponsors discuss the selection and implementation of proposed PRO instruments with the FDA as early as possible during drug development,” the draft reads. Comments on the draft can be submitted over the next two months.
Draft Guidance: Low Sexual Interest, Desire, and/or Arousal in Women: Developing Drugs for Treatment