FDA Panel Recommends Approval of ER Abuse-Deterrent Oxycodone

A US Food and Drug Administration (FDA) advisory committee has recommended approval of a new extended-release, abuse-deterrent oxycodone that may be an advance over similar products.

The members of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 23 to 0 to support approval of Collegium Pharmaceutical’s Xtampza ER(oxycodone extended-release capsules), for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternatives are inadequate.

The extended-release medication offers a potential alternative for millions of people with chronic pain who have trouble swallowing. Unlike the abuse-deterrent form of OxyContin(Purdue), Xtampza ER does not get sticky when wet. And, Xtampza ER cannot be transformed into an immediate-release form, even if it is crushed or chewed. Canton, Massachusetts-based Collegium showed that the medication could be given by breaking open the capsule and pouring the oxycodone microspheres into a feeding tube or sprinkling them onto soft food or directly into the mouth.

“We’ve seen data suggesting the prevalence of dysphagia is substantial in chronic pain patients,” said panelist Brian Bateman, MD, MSc, assistant professor of anesthesia at Harvard Medical School. “This will meet that clinical need.”

Committee members also said that the company had convincingly proven that this formulation would prevent abuse by inhalation or injection. “The abuse deterrence is very promising,” said Anita Gupta, DO, PharmD, vice chair of the division of pain medicine and regional anesthesiology at Drexel University College of Medicine. “It’s progress in the right direction.”

Panelist Raeford Brown, professor of anesthesiology and pediatrics at the University of Kentucky College of Medicine, agreed. “This is a real advance, from what I can determine, in the issue of deterrence of opioid abuse,” he said.

Nananda Col, MD, a principal at Shared Decision Making Resources in Georgetown, Maine, said she thought that while Xtampza ER might not necessarily curb abuse at the population level, it offered an “opportunity to reduce abuse at the individual level.” And, she said,the drug “will make it easier for doctors on the ground floor to prescribe without worrying about it being diverted.”

Unique ER formulation

Because early pharmacokinetic data indicated that taking the drug while fasting substantially lowered its bioavailability, Collegium worked with the FDA on finding a formulation that would minimize those effects.

If approved, Xtampza ER will join four other approved abuse-deterrent ER opioids: OxyContin, Targiniq(oxycodone and naloxone extended-release tablets; Purdue), Embeda (morphine sulfate and naltrexone extended-release capsules; Pfizer), and Hysingla ER (hydrocodone extended-release tablets; Purdue).

According to data from IMS Health cited by the FDA, the number of extended-release oxycodone formulations dispensed by outpatient retail pharmacies has been declining, while single-entity IR oxycodone prescriptions (which do not have abuse-deterrent properties) have been on the rise — up 52%, from 10.4 million in 2010 to 15.8 million in 2014. Prescriptions for extended-release oxycodone declined by about a third over the same period, from 7.3 million in 2010 to 4.7 million in 2014. Most of those were for Purdue’s reformulated abuse-deterrent OxyContin.

Some panelists speculated that ER prescriptions might rise with the availability of Xtampza ER.

Yesterday, members of the panel voted 23 to 1 against allowing Purdue Pharma’s Avridi, the first immediate-release oxycodone tablet to come with abuse-deterrent properties. The panel recommended that the FDA decline approval based on concerns that delayed analgesia due to the antiabuse technology seen when it was taken with food may lead to increased overdose risk.

Phase 3 Data Help Sway Panel

Collegium conducted a number of studies — including in vitro pharmacokinetic studies and randomized human trials — to prove the safety and efficacy of Xtampza ER and also that its abuse-deterrent technology worked.

The FDA’s main concern was whether patients would follow directions to take the medication with food. Less bioavailability with fasting created the potential for adverse events, including overdose.

To better assess how the drug would work in the real world, the company conducted a phase 3 enriched-enrollment, randomized withdrawal, double-blind, placebo-controlled trial comparing Xtampza ER with placebo. The 193 Xtampza ER patients and 196 placebo patients were opioid-naïve or experienced and had moderate-to-severe, chronic lower-back pain for at least 6 months. Those taking Xtampza ER had statistically significantly lower pain scores after 12 weeks.

Patients also kept meticulous electronic food diaries. The company concluded that there was not much variation in medication effectiveness with different diets. And there were no adverse events associated with either eating or not eating.

“Having the phase 3 trial made all the difference in the world,” said panelist Linda Tyler, PharmD, professor and associate dean for pharmacy practice at the University of Utah College of Pharmacy.

“The data from the phase 3 study were very compelling,” agreed Dr Bateman. “It suggests the food effect is forgiving, and unlikely to be of major clinical significance.”