A Food and Drug Administration panel was split Thursday on whether Malvern-based Endo Health Solutions' testosterone drug Aveed was safe enough to be approved.
The FDA is not required to follow votes by advisory committees, but a 9-9 split combined with a 17-1 negative vote on the company's suggested approach for delivering the injectable drug would be a disappointment for the company, which has tried several times to get the drug approved for use in a growing market.
Thursday's gathering was a joint meeting of the Advisory Committee for Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committee Meeting Announcement. The official agenda statement was:
“The committee will discuss the efficacy and safety of new drug application (NDA) 22219, AVEED (testosterone undecanoate) intramuscular injection, submitted by Endo Pharmaceutical Solutions, Inc., for the proposed indication of replacement therapy in adult males for conditions associated with a deficiency or absence of testosterone. The safety discussion will focus on postmarketing reports of oil microembolism in the lungs and potential anaphylactic reactions. In addition to AVEED, other approved testosterone injectable products will be referenced, especially in regard to oil microembolism and potential anaphylactic reactions reported for those products.”
The link to the FDA page on the meeting is here. It has further links to materials prepared by the FDA staff a brief by Endo Pharmaceuticals, the company's drug subsidiary.
The Associated Press story by Matthew Perrone appears below:
By MATTHEW PERRONE
AP Health Writer
WASHINGTON — Federal health experts issued a split opinion Thursday on whether a long-acting testosterone injection from Endo Health Solutions is safe.
A Food and Drug Administration panel voted 9-9 on the safety of Endo’s Aveed, a drug designed to be injected once every 10 weeks to boost testosterone in men with abnormally low levels. The FDA is not required to follow the group’s advice, though it often does.
Endo has asked the FDA to approve its drug as a long-term treatment for hypogonadism, or low testosterone caused by disease or damage to the reproductive or hormonal organs. The condition is associated with fatigue, weight gain, depression and reduced libido.
Estimates for the number of men in the U.S. with low testosterone levels range from 5 million to 30 million, depending on the criteria used. While there are established numbers for typical testosterone levels in younger men, there is no consensus on what is a “normal number,” in older men.
The split panel vote is the latest twist in Aveed’s multiyear review by the FDA. The Malvern, Pa-based drugmaker first submitted the drug in 2007, but the FDA rejected it in 2008 and again in 2009. Regulators have continued to raise concerns about dangerous side effects associated with the injection.
Panelists who voted against the drug said the risks were not outweighed by the benefits of its long-lasting formulation.
“I felt the safety was not quite there yet — admitting that we need a long-term preparation,” said Dr. Bart Clarke, of the Mayo Clinic in Rochester, Minn.
The Endo injection is to be taken once every 10 weeks, versus weekly or biweekly for currently available products.
Panelists who backed the drug pointed out that it has been approved in Europe since 2003 without any reports of death.
In review documents released earlier in the week, the FDA repeated its concerns about two types of problems seen in company studies: allergic reactions and micro embolisms.
The allergic reactions can cause painful skin symptoms, difficulty breathing and loss of consciousness. The embolisms can cause dangerous breathing problems when tiny droplets of oil from the injection travel to the lungs.
The company suggested those issues could be addressed with labeling instructions that doctors inject the drug “very slowly,” and monitor patients for 30 minutes afterwards.
Panelists rejected that approach by a vote of 17 to 1 because it would not alleviate the risk of side effects.
The FDA also appeared to rule out the company’s plan in its review.
“There are no known approaches to predict or prevent the occurrence of an Aveed-related severe post-injection reaction for any patient,” the FDA stated in briefing documents posted Tuesday.
Drug companies have increasingly targeted low testosterone as a new market opportunity, running television and magazine ads about the impact of low testosterone on aging men.
Testosterone drug sales have increased 90 percent in the last five years to roughly $2 billion annually, mainly driven by new creams and gels, including Endo’s Fortesta.
Shares of Endo Health Solutions Inc. fell 21 cents to close at $35.75.