FDA Sticks To Hard Line On Abuse-Deterrent Opioids; Acura Takes A Hit
This article was originally published in The Pink Sheet Daily
Executive Summary
Acura Pharmaceuticals’ stock fell 11% May 28 after the company revealed that FDA advised an abuse liability study for its hydrocodone/acetaminophen product would not support an abuse liability claim.
FDA is maintaining its hard stance on abuse-deterrent claims for opioids that incorporate technologies designed to thwart abuse, this time spurning an Acura Pharmaceuticals Inc. product. The company announced May 28 that FDA advised it that data from an intranasal abuse liability study testing its abuse-deterrent hydrocodone/acetaminophen product candidate would not be sufficient to support a claim of abuse-deterrence.
The advice letter is bad news for Acura, although not entirely unexpected given that the study in question did not meet its primary endpoint. The company needs an abuse-deterrent claim for the product to differentiate it from other hydrocodone/acetaminophen products on the market, most notably Percocet, which is available as a cheap generic.
Acura had been awaiting guidance on the abuse-liability study before filing an NDA for the product and hopefully finding a marketing partner. The company’s stock dropped 11% on the news to close the day at $1.12.
The firm plans to meet with FDA to discuss next steps and will update investors on a revised timeline for an NDA submission after the meeting.
“We are putting together our request presently and given the criticality of the issue, we are hoping the FDA will meet with us in short order,” CEO Robert Jones said in an interview. More clarity likely would be needed from FDA before a potential partner would commit to marketing the drug, effectively tabling such discussion for now.
The specialty pharma met with FDA in December to discuss the results from Study 301, a Phase II trial that assessed the abuse liability of snorting a crushed hydrocodone/acetaminophen tablet formulated with Acura’s abuse-deterrent Aversion technology in 40 recreational drug abusers (Also see "In Challenging Opioid Market, Acura Still Seeks A Partner" - Pink Sheet, 7 Nov, 2013.). The results showed the Aversion product had a slightly lower numeric mean maximum drug liking compared to an equivalent dose of a marketed generic version of hydrocodone/acetaminophen, but the results were not statistically significant.
FDA determined the data were insufficient and that a product has to have an impact on drug liking to support a claim of abuse, the company said in a release. FDA also questioned whether the intranasal route is a relevant route of abuse for hydrocodone/acetaminophen products versus abuse through injection and recommended that Acura identify variables that could have impacted the findings from the study before conducting an additional one.
Acura found the question about the route of abuse surprising given that hydrocodone products are recognized as the most widely abused and research in the literature shows 18% of the abuse is via snorting. “It has really come out of the blue,” Jones said, noting that FDA did not question the route of abuse used in the study during the December meeting.
Acura already is preparing for a new study, perhaps using a parallel design instead of a crossover design, which FDA has suggested could be the more appropriate design in guidance issued in January 2013 on abuse-deterrent opioids (Also see "FDA’s Opioid Guidance: Industry Celebrates Multi-Tiered Labeling Cake" - Pink Sheet, 14 Jan, 2013.).
Partnering Plans Still On For Oxycodone
The setback comes as Acura had picked up some momentum in recent weeks. In April, the company announced that it had reached an agreement with Pfizer Inc. to terminate its license to Acura’s Aversion technology and return rights to a different crush-resistant product, Oxecta (oxycodone). Pfizer acquired the immediate-release oxycodone product when it bought King Pharmaceuticals Inc. for $3.3 billion in late 2010, but the drug languished at Pfizer.
The hydrocodone/acetaminophen product previously was returned to Acura by the big pharma, which returned rights to three products made with the Aversion technology in 2012. Acura agreed to pay $2 million to Pfizer in the most recent arrangement, though Pfizer will maintain ownership of the brand name. Oxecta generated less than $250,000 in 2013, according to Acura.
Jones said the company is moving ahead with partnering discussions for the product and expects it will re-enter the market by the end of the year.
Pfizer largely has been unsuccessful capitalizing on King’s abuse-deterrent pain portfolio, in part because of the high regulatory hurdles at FDA for getting opioid drugs approved with abuse-deterrent claims (Also see "The Best Bad Deal of All Time? Pfizer/King and the Business Dynamics of Abuse Deterrence" - Pink Sheet, 30 May, 2013.). FDA’s leadership has been forthright about the challenges in the space, despite recognizing the need for abuse-deterrent medicines. Commissioner Margaret Hamburg called abuse-deterrent technology “poor” during testimony to a Senate committee in March (Also see "Abuse-Deterrent Testimony: Hamburg Defends Opioid Policy On The Hill" - Pink Sheet, 14 Mar, 2014.).
Acura is far from the only company that has struggled to get abuse-deterrence claims for opioid drugs recognized by FDA. So far only one product, Purdue Pharma LP’s OxyContin (oxycodone controlled-release), includes abuse-deterrent claims in labeling (Also see "Opioid Market Snapshot: No Pain, No Gain For Abuse-Deterrence Claims" - Pink Sheet, 24 Mar, 2014.).