- At least three reviewers recommended against Addyi approval
- Managers determined benefit of the drug outweighs the risk
Addyi, the pink pill for women with low libido, was approved by the Food and Drug Administration last month even though at least three FDA reviewers recommended rejecting it.
They warned about possible side effects and expressed concern that “the marginal clinical benefits do not outweigh the serious risks,” according to a memo posted online that summarized the analysis within the U.S. regulatory agency. More than a dozen offices reviewed the drug, though the memo doesn’t make clear how many people raised concerns. One reviewer particularly wanted more study of the interaction between Addyi and alcohol because the tests were conducted almost exclusively with men.
While such disagreement isn’t typical, “it does happen,” said Ira Loss, a pharmaceutical analyst with Washington Analysis, a research company that evaluates the impact of public-policy change on financial markets. The FDA had rejected the drug, chemically known as flibanserin, in 2010 and 2013 before approving it in August, so the dissenters were “not alone in their view. FDA gives them the right to say what they feel, and higher-ups make the decision.”
Two years ago, there was internal dissent when the FDA approved Bristol-Myers Squibb Co. and Pfizer Inc.’s blood thinner Eliquis. A decade ago, there also was division over the safety of Merck & Co.’s Vioxx painkiller, which has since been taken off the market, and Sanofi’s antibiotic Ketek.
“The FDA encourages robust scientific discussions among our staff,” Andrea Fischer, an FDA spokeswoman, said in an e-mail. “In most cases, alignment on a decision is achieved through discussion as reviews proceed,” but the official administrative file will reflect “differences of opinion if they exist.”
Tension inside the high-stakes discussion about Addyi, which will be available as soon as Oct. 17, echoes public debate that pitted even women’s advocates against each other. Some encouraged approval because no other drugs are available for women with low libido. But Addyi, made by Sprout Pharmaceuticals Inc., offers meaningful help for only about 10 percent more patients than a placebo, according to the memo. It also can cause low blood pressure and fainting, especially if patients drink alcohol while taking it.
While Addyi has become known as the "female Viagra," it’s different from Pfizer’s best-selling erectile dysfunction drug because it targets the brain to increase desire, while the male pill simply helps men who already want to have sex. When FDA advisers met in June, they heard from women who argued they should be allowed to weigh Addyi’s risks themselves.
Hylton Joffe, director of the FDA’s Division of Bone, Reproductive and Urologic Products, recommended approving the drug and wrote the memo that summarizes all the reviews. In it, he said he took into account that no similar drugs for women have been accepted and said the risks can be reasonably managed with a strategy Sprout will implement: Doctors who prescribe Addyi must take an online training course, and patients must sign a form acknowledging the risks.
These risks include the potential side effects related to alcohol, which prompted the FDA to require a warning on the drug’s label. Sprout studied the interaction on 23 men and two women. According to the memo, the official who led day-to-day management of the FDA review said a study on women taking Addyi should have been done before approval.
“This approach is not unreasonable but, in my view, is not required because flibanserin is being approved, assuming that the alcohol interaction in women is at least as severe as the alcohol interaction in men,” Joffe wrote in the memo. “We will continue to assess the risk-mitigation approaches as more data become available.”
The FDA approved Addyi with the understanding that there will be three post-market studies with women, the agency said in a press release. Valeant Pharmaceuticals International Inc. agreed to acquire Sprout last month for about $1 billion.
Patients take the drug every night before bed, so the likelihood women will abstain from alcohol while on Addyi is low, given that the Centers for Disease Control and Prevention says half of all women in the U.S. drink. The centers also have explained alcohol’s different impact on men and women.
“Upon drinking equal amounts, women have higher alcohol levels in their blood than men, and the immediate effects occur more quickly and last longer,” according to an online CDC fact sheet.“These differences also make women more vulnerable to alcohol’s long-term effects on their health.”
Joffe wrote that he didn’t consider claims of gender bias in deciding whether to approve Addyi. He said his decision was “based solely” on efficacy and safety data and the benefit/risk assessment. This can vary among FDA experts based on “variations in clinical and scientific judgments,” which can “lead to differing individual opinions and conclusions.”
“This is the situation facing the flibanserin application: There is internal agreement on the facts, but not on whether the demonstrated benefits outweigh the known risks,” he wrote.
(An earlier version of this story corrected the description of Addyi’s effect on blood pressure.)