Pfizer will follow up on the FDA approval of the re-formulated Oxecta (oxycodone HCl), which is designed to be abuse-resistant, with an epidemiological study of whether the immediate-release opioid decreases misuse and abuse and resultant overdose, addiction and death.

The post-market study is attached to FDA's June 17 approval of the drug, which originally was developed as oxycodone plus niacin and named Acurox.

King Pharmaceuticals, since acquired by Pfizer, removed the niacin component from Acurox following the conclusion by FDA and an advisory panel that addition of the B vitamin did not deter abuse (Also see "Advisory Committee Sides With FDA: King/Acura's Acurox Fails To Prevent Abuse" - Pink Sheet, 22 April, 2010.).

However, the advisory committee did appreciate the other abuse-deterrent properties of the product - the addition of sodium lauryl sulfate to make sniffing the drug in crushed form unpleasant, and an excipient that, if the drug is dissolved in liquid, will to turn it into a gel that cannot be easily injected. Both are based on technology from Acura Pharmaceuticals.

King submitted a new NDA for the re-formulated Oxecta in December 2010.

Details of what FDA expects in the Oxecta study are not available. But the complexity of the task is indicated by early proposals for studies of King's extended-release Embeda (morphine sulfate/naltrexone) (Also see "Embeda's Proposed Epidemiological Study Program" - Pink Sheet, 1 November, 2010.) and Purdue's continuous-release OxyContin (oxycodone) (Also see "OxyContin's Planned Epidemiological Study Program" - Pink Sheet, 1 November, 2010.), which were discussed during an advisory committee in 2010.

Label Includes Language, But No Abuse-Resistant Claim

The studies are needed to support claims of abuse-resistance that have eluded sponsors. Such claims may not even be possible, according to the advisory committee, which concluded that abusers will find a way to abuse any product and the best that can be hoped for is a statement about specific characteristics, such as injection-resistance (Also see "Opioid Abuse-Deterrence Labeling May Be A Long Way Off After Panel Rejects Validity Of Broad Claim" - Pink Sheet, 22 October, 2010.).

FDA has, however, allowed information about studies of abuse resistance into labeling.

In the case of Oxecta, the Drug Abuse and Dependence section notes that a crossover study with 40 non-dependent recreational opioid users found a lower likeability for Oxecta compared to immediate-release oxycodone, although the differences in the median and mean scores were small numerically. Both drugs were crushed and self-administered intranasally.

Study participants reported a higher incidence of nasopharyngeal and facial adverse events with Oxecta and an impaired ability to self-administer the drug; 30% of those exposed to Oxecta said they would not take it again, compared to 5% of those exposed to immediate release oxycodone.

The label adds that the clinical significance of these differences has not yet been established and "there is no evidence that Oxecta has a reduced abuse liability compared to immediate-release oxycodone."

Labeling for Embeda, which currently is off the market because of manufacturing problems, also has information about studies of drug-likeability and euphoria. Again, the labeling notes "there is no evidence that the naltrexone in Embeda reduces the abuse liability of Embeda."

FDA has another opportunity to write an opioid label as it considers Pain Therapeutics' Remoxy, a long-acting oxycodone with a June 23 PDUFA date. The company unveiled data from an abuse liability study for the drug in April (Also see "Remoxy's Abuse Liability Study May Offer Clues On FDA's Upcoming Opioid Guidance" - Pink Sheet, 2 May, 2011.).

Commercial launch of Oxecta, which is indicated for management of acute and chronic moderate to severe pain where the use of an opioid analgesic is appropriate, is expected in the late third quarter or early fourth quarter of this year. Acura will receive a $20 million milestone payment from Pfizer for the FDA approval.

-Cathy Dombrowski (c.dombrowski@elsevier.com )

Pfizer Will Study Oxecta Abuse/Misuse Potential Post-Market

More from Archive

More from Pink Sheet