Endo International’s strategy of reformulating its opioid painkiller Opana ER to make it less prone to abuse has backfired spectacularly. Apparently prompted by panellists’ concerns that the new formulation is actually more dangerous than the previous version, the FDA has asked Endo to withdraw the drug in the US. Endo’s shares are down 16% in early trading.
It is not yet clear whether Endo will accede to the request. Should it refuse to pull the drug, the FDA can in theory take legal action to force the withdrawal. And, if Opana ER does become the first opioid to be withdrawn, it might not be the last – the FDA said it would continue to look at the risk-benefit profile of all approved opioid analgesics “and take further actions as appropriate”.
Back in March an FDA panel voted 18 to eight that Opana ER’s benefits no longer outweigh its risks. At the time concerns were voiced that Endo’s reformulation of the extended-release oxymorphone to make it harder to crush and inhale made addicts dissolve and inject it instead, thereby contracting serious disorders including HIV and hepatitis C (Event – FDA panel to re-examine Opana ER, March 9, 2017).
Still, it was far from clear at that point that the agency would ask for the drug’s withdrawal. The agency has an uneven history when it comes to opioids: in 2013 it approved Zogenix’s hydrocodone formulation Zohydro ER, despite an adcom recommending against the approval owing to its potential for abuse.
The opiate of the people
The FDA now says a review of postmarketing data proves the suspected shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation. Endo altered the drug’s formulation in 2012 to try to hook FDA designation as abuse-resistant and thus increase sales. The agency was unconvinced.
Endo says it is reviewing the FDA’s request and is “evaluating the full range of potential options” for the drug. But some industry watchers believe the drug’s days are numbered: analysts from Janney wrote that “while timing remains uncertain, it is clear Opana ER will be removed from the market”.
If so, Endo will lose its second biggest seller. Opana ER brought in revenue of $159m last year – about 4% of Endo’s total sales – all of it in the US.
And other companies may need to worry. Nine opioid painkillers outsell Opana ER, and if the FDA decides to take the same attitude to them their US sales could be at risk. Fentanyl, vastly more powerful than even heroin, has particularly exercised lawmakers, and it could be argued that products such as Insys Therapeutics’s Subsys may attract the agency’s attention.
That said, it could be that this situation is unique to Endo – and if that turns out to be the case, the reformulation looks like a very bad misstep.
|Top 10 currently marketed opioid painkillers by 2022 sales|
|Annual WW sales ($m)|
|Nucynta ER||tapentadol hydrochloride||Depomed||281||457||+8%|
|Xtampza ER||oxycodone hydrochloride||Collegium Pharmaceutical||1||327||+146%|
|Embeda||morphine sulfate; naltrexone hydrochloride||Pfizer||168||291||+10%|
|Troxyca ER||naltrexone hydrochloride; oxycodone hydrochloride||Pfizer||3||263||+115%|
|Subsys||fentanyl citrate||Insys Therapeutics||242||180||-5%|
|Duragesic||fentanyl||Johnson & Johnson||288||163||-9%|
|Hydromorphone Hydrochloride||hydromorphone hydrochloride||Pfizer||133||154||+2%|
|Nucynta||tapentadol hydrochloride||Grünenthal Gruppe||117||151||+4%|
|Fentanyl Transdermal System||fentanyl||Mylan||208||139||-6%|
|Opana ER||oxymorphone hydrochloride||Endo International||159||127||-4%|