Abuse of opioid painkillers has reached epidemic proportions in many areas of the US, and the FDA is under enormous political pressure to do something about it. With this in mind the agency is to convene a panel on March 13, 14 examining formulations of oxymorphone, with particular emphasis on Endo International's Opana ER.
Both the FDA and Endo declined to state, when asked, whether there was any prospect of Opana ER being removed from the US market. But this does appear to be a possibility, with Opana ER coming under particular scrutiny over its safety and abuse potential – despite Endo’s attempts to make it resistant to abuse.
Endo’s immediate-release form of oxymorphone, Opana, was approved in 2006. When the patent expired in 2011 the company was ready with an extended-release version, the patent for which will not fall until 2023.
Endo has since attempted to win a label claim for abuse deterrence, saying Opana ER is resistant to being crushed or dissolved to extract the drug for snorting or injection to produce a high. A legal change proposed in 2012 that would have forced non tamper-resistant versions off the market the instant an abuse-resistant formulation was approved never made it on to the statute books (Political backing unlikely to help developers of tamper-resistant painkillers, August 9, 2012).
Nevertheless, an abuse-resistant label claim – with careful pricing – could have boosted sales. But Endo pulled the sNDA application for specific abuse-deterrent labelling last summer, saying it would gather more clinical data. The company has not yet re-filed this, and it declined to say whether it might in future.
Instead of seeking an enhanced label, Endo might now have to fight for Opana ER’s continued existence on the market. The panel will vote on whether the benefits of Opana ER continue to outweigh its risks. If the vote is a no, presumably the panel will recommend that the agency yank the drug from sale.
It appears that Endo at least does not anticipate market withdrawal, given that its 2017 outlook still includes Opana ER sales. But there are serious safety concerns with Opana ER in particular.
According to the FDA, the panel will discuss safety issues related to the drug, including a warning about serious blood disorders seen in people who abused Opana ER. In October 2012 the FDA said individuals in Tennessee who had dissolved the pill and injected the drug experienced thrombotic thrombocytopenic purpura, a disorder in which blood clots form in the microvasculature. A CDC report on 15 such cases followed in 2013.
More recently, another CDC report linked 108 cases of HIV infection with abuse of extended-release oxymorphone. No particular brand was specified, but it is highly likely that at least some of the patients abused Opana ER.
It has been suggested that Opana ER’s anti-abuse coating might actually be contributing to these outbreaks. This makes the pill harder to crush, so addicts cannot inhale the powder. Instead they dissolve the pill and inject the solution, putting them at risk of needle-borne diseases.
Endo does not expect the pill to be forced from the market, and analysts from Leerink and Mizuho regard this as a remote possibility too. However, Mizuho believes that the FDA might insist on more restrictive labelling, presumably cutting into Opana ER’s sales, which came to $159m last year.
Still, a remote possibility is still a possibility. Pulling Opana ER might be a heavy-handed – and only partial – solution to the opioid addiction problem, but the FDA, the CDC and many US politicians are united in the belief that something must be done.
|FDA-approved oxymorphone formulations|
|Global sales ($m)|
|Product||Company||Product type||2016||2022||US launch|
|Opana ER||Endo International||NDA + proprietary drug delivery||159||124||Dec 12, 2011|
|Opana*||Endo International||NDA||-||-||Jun 22, 2006|
|Oxymorphone Hydrochloride ER||Teva Pharmaceutical Industries||Generic||16||9||Jun 30, 2016|
|Oxymorphone Hydrochloride||Aurobindo Pharma||Generic||-||-||Apr 26, 2016|
|Oxymorphone||Mallinckrodt||Generic||-||-||Apr 25, 2013|
|Oxymorphone Hydrochloride||Avanthi||Generic||-||-||Jan 30, 2013|
|Oxymorphone Hydrochloride XR||Sun Pharmaceutical Industries||Generic||-||-||-|
|Oxymorphone Hydrochloride ER||Hikma Pharmaceuticals||Generic||-||-||-|
|*sales of Opana included in figures for Opana ER.|
This story has been amended to remove an incorrect statement that Opana ER was licensed to Grünenthal in the US. Grünenthal licensed the abuse-deterrent technology used to develop the drug.