New FDA Guidelines Could Revive Debate Over ‘Female Viagra’

FDA sent Addyi’s application back to its manufacturer twice for changes

Posted October 26, 2016 at 7:25pm

A draft guidance that the Food and Drug Administration published Tuesday could revive a debate about a drug approved last year to enhance the female libido. At the time of the approval, many observers questioned the FDA’s decision and doubted that the drug actually works. Now, some of the same critics are wondering whether or not the product, called Addyi and nicknamed the “female Viagra,” would even live up to the agency’s newly proposed criteria.

For instance, the draft guidance suggests that patients participating in clinical trials should frequently record key signs and symptoms “to minimize inaccurate responses resulting from problems” with a patient’s ability to recall past feelings. The guidance doesn’t specify just how long the recall period should be, but it hints that a shorter one is more desirable. “The longer recall period may increase noise in the assessment making it more difficult to detect or interpret change during a trial. With a longer recall, it is also possible that subject recollection could be more heavily influenced by other experiences or by more recent experiences,” the guidance says.

Addyi was approved on the basis of data collected on a longer-term basis, asking patients questions such as, “Over the past 4 weeks, how often did you feel sexual desire or interest?” Researchers asked a similar question about how strong the desire or interest was during the same time period.

The FDA had sent Addyi’s application back to its manufacturer twice for changes before finally approving it. Earlier applications included evidence based on daily reporting, and that reporting didn’t meet the FDA’s efficacy standards.

“When women reported their signs and symptoms in a daily diary, Addyi was not effective. It was only when they measured it on a monthly basis that there was a statistically significant benefit,” explained Diana Zuckerman, president of the National Center for Health Research, a nonprofit advocacy organization. “It’s difficult for any of us to accurately remember how we felt during the last month. It will be strongly influenced by how we felt the last week or two.”

The FDA guidance also expresses concerns about how to measure an improvement in sexual desire or arousal. For example, the guidance says that if the drug can result in increased sexual fantasies, but does not improve whether a patient is receptive to sexual activity, that could still result in ”a score change suggesting improvement could be shown; however, it is unclear whether this represents a meaningful benefit to patients.”

Another measure for consideration is the change in number of satisfying sexual events. In the approval announcement for Addyi, the FDA said that the drug only resulted in one extra satisfying sexual event per month more than a placebo.

Supporters of the drug say that the clinical targets or endpoints studied in Addyi’s approval — the indications the drug is working — would remain valid under the new guidance. “The endpoints used, primary and secondary, would still be considered in new draft guidance;” said Sally Greenberg, the National Consumers League’s executive director and a frequent speaker at FDA public meetings.

Greenberg also noted that the new guidance could also give more weight to evidence showing that a drug reduces sexual distress but doesn’t necessarily increase the number of satisfactory sexual events.

The FDA approved the drug in August 2015, following the recommendation of an independent advisory panel. The decision was preceded by lobbying from lawmakers and women’s groups who felt gender bias at the FDA resulted in the agency holding libido drugs for women to a higher standard than similar drugs for men. Many argued that it should be up to women and their doctors whether it was worth it to face the associated risks, which include low blood pressure, loss of consciousness, dizziness and nausea. Women who take Addyi are advised to abstain from alcohol while taking the drug, and the FDA is requiring additional trials to examine the drug’s interaction with alcohol.