The US Food and Drug Administration on Thursday requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market due to public health concerns over abuse.
"After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks," FDA said.
The move to call on a company to remove a drug for reasons of safety or effectiveness is a relative rarity for FDA (and one of the first for an opioid). A review from 2015 of drugs pulled from the market found that between 1996 and 2005, there were 66 withdrawals, of which just two were for reasons of safety or effectiveness. In comparison, between 2006 and 2015, there were 149 withdrawals, of which nine were for reasons of safety or effectiveness.
But new FDA commissioner Scott Gottlieb last month said his immediate priority is to target opioid abuse and he has established a commission to come up with new ways of dealing with the crisis.
Endo said in a statement on Thursday that it’s "reviewing the request and is evaluating the full range of potential options as we determine the appropriate path forward … Despite the FDA's request to withdraw Opana ER from the market, this request does not indicate uncertainty with the product's safety or efficacy when taken as prescribed. Endo remains confident in the body of evidence established through clinical research demonstrating that Opana ER has a favorable risk-benefit profile when used as intended in appropriate patients."
According to an FDA review of postmarketing data, FDA said there was "a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation. Injection abuse of reformulated Opana ER has been associated with a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy). This decision follows a March 2017 FDA advisory committee meeting where a group of independent experts voted 18-8 that the benefits of reformulated Opana ER no longer outweigh its risks."
FDA also said Thursday that if Endo chooses not to remove Opana ER from the market, the agency "intends to take steps to formally require its removal by withdrawing approval. In the interim, the FDA is making health care professionals and others aware of the particularly serious risks associated with the abuse of this product."
First approved by FDA in 2006, in 2012 Endo replaced the original formulation of Opana ER with a new one intended to make the drug resistant to physical and chemical manipulation for abuse by snorting or injecting.
But FDA determined that the data did not show that the reformulation could be expected to meaningfully reduce abuse and declined the company’s request to include labeling describing potentially abuse-deterrent properties for Opana ER.
In 2013, the Centers for Disease Control and Prevention (CDC) reported 15 cases in Tennessee of thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse.
"The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market," said Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research. "This action will protect the public from further potential for misuse and abuse of this product."
But whether FDA will halt the marketing of other opioids remains unknown. In April, FDA approved RoxyBond, the first immediate-release opioid analgesic approved with labeling describing its abuse-deterrent properties. FDA said Thursday it "will continue to examine the risk-benefit profile of all approved opioid analgesic products and take further actions as appropriate as a part of our response to this public health crisis."