FDA Panel Likes New Abuse-Deterrent Opioid

http://www.medpagetoday.com/Neurology/PainManagement/53528?xid=nl_mpt_DHE_2015-09-14&eun=g578717d0r

WASHINGTON — In a second joint meeting of two FDA advisory committees, all 23 panelists voted unanimously to approve an abuse-deterrent formulation of extended-release oxycodone (Xtampza).

Panelists felt that the new formulation, which is comprised of tiny microspheres of drug collected inside a capsule, would pose a significant advantage for the large number of chronic pain patients who have difficulty swallowing pills — without any additional safety risk posed by the need to take the drug with food.

Giving dysphagia patients opioids has been a challenge with other abuse-deterrent products because these properties prevent crushing, a common route of abuse. The new capsule, on the other hand, can be opened and sprinkled into food or delivered via feeding tube.

“Overall I think this is not only an incremental advance, but a step forward from the available products we have,” said panelist Sharon Walsh, PhD, of the University of Kentucky.

“A large number of patients are going to take this drug because they have swallowing disorders, and it will become the go-to drug,” said panelist Raeford Brown, MD, also of the University of Kentucky. “It’s an advance in abuse-deterrence and I think we will see a meaningful reduction in abuse with this drug.”

Drugmaker Collegium Pharmaceuticals presented evidence from pharmacokinetic studies as well as a phase III randomized controlled trial, both of which suggested that the drug would be hard to abuse via the intranasal or intravenous routes.

Those studies did, however, show that Xtampza’s bioavailability is increased when taken with food. Panelists did express concerns that fluctuations in oxycodone blood levels could occur if patients weren’t careful about how they took the drug, but ultimately they were reassured by safety data from the clinical study.

“The phase III study was well conducted, there was efficacy based on pain scores across meals, and the low rate of adverse events suggests the food effect is forgiving and unlikely to be of major clinical significance,” said panelist Brian Bateman, MD, of Harvard.

That conclusion differed vastly from Thursday’s joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, which evaluated Purdue Pharma’s abuse-deterrent, immediate-release oxycodone formulation. That drug had the opposite problem — it had diminished bioavailability when taken with food. Panelists were so concerned that patients would take the drug incorrectly — potentially leading to overdose if they took too much from not feeling an immediate response if taken with food — that they voted nearly unanimously (23 to 1) against approval.

The FDA said it initially advised Collegium to reformulate the product to avoid the food effect, but its final version was still susceptible to increased bioavailability with food, so the agency recommended the additional clinical studies to demonstrate safety when taken with food.

If approved, Xtampza will join four other abuse-deterrent extended-release opioids on the market, including three from Purdue — OxyContin, Targiniq, and Hysingla — and Pfizer’s Embeda.

But Judy Staffa, PhD, RPh, director of epidemiology in the office of pharmacovigilance at the FDA, warned that abuse-deterrent formulations have not yet proven that they diminish opioid abuse in the real world.

Earlier this year, Purdue Pharma pulled an application and cancelled a related FDA advisory committee meeting that was supposed to evaluate “postmarketing studies evaluating the misuse and/or abuse of reformulated OxyContin” and whether those studies “have demonstrated that the reformulated product has a meaningful impact on abuse.”

Filed under: General Problems