Expert Commentary
Flibanserin is poised for FDA approval. But why this drug? And why now?
Women with hypoactive sexual desire disorder have long sought a remedy for this common complaint. With an advisory committee recommending approval...
It was a long road to approval by the US Food and Drug Administration (FDA), but flibanserin (Addyi) got the nod on August 18, 2015. Its New Drug Application (NDA) originally was filed October 27, 2009. The drug launched October 17, 2015.
Although there has been a lot of fanfare about approval of this drug, most of the coverage has focused on its status as the “first female Viagra”—a less than accurate depiction. For a more realistic and practical assessment of the drug, OBG Management turned to Michael Krychman, MD, executive director of the Southern California Center for Sexual Health and Survivorship Medicine in Newport Beach, to determine the types of information clinicians need to know to begin prescribing flibanserin. This article highlights 11 questions (and answers) to help you get started.
1. How did the FDA arrive
at its approval?
In 2012, the agency determined that female sexual dysfunction was one of 20 disease areas that warranted focused attention. In October 2014, as part of its intensified look at female sexual dysfunction, the FDA convened a 2-day meeting “to advance our understanding,” reports Andrea Fischer, FDA press officer.
“During the first day of the meeting, the FDA solicited patients’ perspectives on their condition and its impact on daily life. While this meeting did not focus on flibanserin, it provided an opportunity for the FDA to hear directly from patients about the impact of their condition,” Ms. Fischer says. During the second day of the meeting, the FDA “discussed scientific issues and challenges with experts in sexual medicine.”
As a result, by the time of the FDA’s June 4, 2015 Advisory Committee meeting on the flibanserin NDA, FDA physician-scientists were well versed in many nuances of female sexual function. That meeting included an open public hearing “that provided an opportunity for members of the public, including patients, to provide input specifically on the flibanserin application,” Ms. Fischer notes.
Nuances of the deliberations
“The FDA’s regulatory decision making on any drug product is a science-based process that carefully weighs each drug in terms of its risks and benefits to the patient population for which the drug would be indicated,” says Ms. Fischer.
The challenge in the case of flibanserin was determining whether the drug provides “clinically meaningful” improvements in sexual activity and desire.
“For many conditions and diseases, what constitutes ‘clinically meaningful’ is well known and accepted,” Ms. Fischer notes, “such as when something is cured or a severe symptom that is life-altering resolves completely. For others, this is not the case. For example, a condition that has a wide range of degree of severity can offer challenges in assessing what constitutes a clinically meaningful treatment effect. Ascertaining this requires a comprehensive knowledge of the disease, affected patient population, management strategies and the drug in question, as well as an ability to look at the clinical trial data taking this all into account.”
“In clinical trials, an important method for assessing the impact of a treatment on a patient’s symptoms, mental state, or functional status is through direct self-report using well developed and thoughtfully integrated patient-reported outcome (PRO) assessments,” Ms. Fischer says. “PROs can provide valuable information on the patient perspective when determining whether benefits outweigh risks, and they also are used to support medical product labeling claims, which are a key source of information for both health care providers and patients. PROs have been and continue to be a high priority as part of FDA’s commitment to advance patient-focused drug development, and we fully expect this to continue. The clinical trials in the flibanserin NDA all utilized PRO assessments.”
Those assessments found that patients taking flibanserin had a significant increase in “sexually satisfying events.” Three 24-week randomized controlled trials explored this endpoint for flibanserin (studies 1–3).
As for improvements in desire, the first 2 trials utilized an e-diary to assess this aspect of sexual function, while the 3rd trial utilized the Female Sexual Function Index (FSFI).
Although the e-diary reflected no statistically significant improvement in desire in the first 2 trials, the FSFI did find significant improvement in the 3rd trial. In addition, when the FSFI was considered across all 3 trials, results in the desire domain were consistent. (The FSFI was used as a secondary tool in the first 2 trials.)
In addition, sexual distress, as measured by the Female Sexual Distress Scale (FSDS), was decreased in the trials with use of flibanserin, notes Dr. Krychman. The Advisory Committee determined that these findings were sufficient to demonstrate clinically meaningful improvements with use of the drug.
