FDA Advisors Vote Against Two Drugs for Menopausal Hot Flashes

Advisers to the Food and Drug Administration on Monday voted against approval of two drugs designed to reduce the frequency and severity of hot flashes associated with menopause, concluding that neither conferred enough benefit to offset their risk.

The panel voted 12-2 against a drug made by Depomed Inc, sending the company’s shares down 9.8 percent to $5.89 on the Nasdaq. Depomed’s shares fell as low as $5.12 immediately after they resumed trading following a halt pending the results of the panel’s meeting.

The panel also voted 10-4 against approving a drug for hot flashes made by Hisamitsu Pharmaceutical Co Inc’s subsidiary Noven Pharmaceuticals Inc.

The drugs would have been the first non-hormonal therapies for hot flashes to have been approved by the FDA. The use of hormone therapy has dropped significantly since 2002, when findings from a large clinical trial showed the therapies could increase the risk of heart attack and stroke.

Hot flashes affect some 75 percent of the estimated 32 million women in the United States experiencing menopause each year, Depomed said. Hot flashes, characterized by warmth, flushing and sweating, can be disruptive, and can last anywhere from a few years to more than a decade.


Depomed’s drug, Sefelsa, is a long-acting version of the epilepsy drug gabapentin. A short-acting version of gabapentin, made by Pfizer Inc and marketed as Neurontin, was approved in 1993.

Clinical trials of Sefelsa showed it only partially reduced the frequency and severity of hot flashes, while side effects included dizziness, sleepiness, headache and nausea. Gabapentin has also been shown to increase the risk of suicide.

Similarly, Noven’s drug did not meet all the goals it was supposed to meet in a clinical trial and panel members felt it was difficult to assess how beneficial the treatment was since many patients taking the placebo also improved.

The FDA does not have to follow the recommendations of its advisory panels, but it generally does.

Depomed said it would cease spending on Sefelsa.

“We recognize and appreciate the concerns that were raised by the members of the Advisory Committee,” Jim Schoeneck, Depomed’s chief executive officer, said in a statement. “Based on today’s meeting, we believe the hurdles for approval of a non-hormonal treatment for hot flashes remain high.”

Extended-release gabapentin was approved in the United States in 2011 to treat shingles-related pain. It is marketed by Depomed under the brand Gralise.

Noven’s drug comprises a low dose of the antidepressant paroxetine mesylate. The company sells a higher-dose version of the drug under the brand Pexeva for, among other things, depression, obsessive-compulsive disorder and generalized anxiety. A similar drug, Paxil, is made by GlaxoSmithKline Plc.

“The FDA’s advisors did a great job today of carefully considering the scientific evidence,” said Diana Zuckerman, president of the National Research Center for Women & Families, a nonprofit organization that promotes health and safety of children and adults.

“We strongly urge the FDA to listen to these advisors and reject the applications of both companies.”

Risks associated with paroxetine include an increase in suicidal thinking.

“While we are disappointed in today’s outcome, we appreciate the discussion and will work closely with the FDA as it completes its ongoing evaluation,” said Dr. Joel Lippman, Noven’s chief medical officer.

He reiterated the company’s belief that the trial data support the use of the drug as safe and effective.

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