FDA Advisory Committees Spurn Purdue Pharma’s NDA for Avridi
Two FDA advisory committees voted 23 to 1 last week not to recommend approval of Purdue Pharma’s NDA for Avridi, saying the public health benefits of the abuse-deterrent opioid don’t outweigh the risks to patients posed by the effect of food intake.
Avridi is one of two abuse-deterrent opioids the panels are considering this week. They met last week to discuss Collegium Pharmaceuticals’ Xtampza ER oxycodone capsule, which — like Avridi — also carries risks if taken on an empty stomach. The abuse-deterrent properties of Xtampza differ from those of Avridi, however, so the panel will have to consider whether its benefits outweigh the risks.
For immediate-release Avridi (oxycodone), gelling agents activate when the drug is mixed with a liquid to prevent intravenous abuse. It also contains sodium laurel sulfate, which causes a burning sensation if snorted. However, panel members pointed out that the majority of abusers take opioids orally.
Members of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee also worried that Avridi’s slowed absorption when taken with food could affect safety and efficacy. Purdue has proposed labeling saying the drug should be taken on an empty stomach, but FDA reviewers said patients may have difficulty finding a time window to take it, since it is intended to be dosed every four to six hours.
On a full stomach, the median time to peak exposure with Avridi was roughly four hours, with a range of one to nine hours, compared with roughly 1.5 hours and a range of 0.5 to 4 hours for reference product Roxicodone (immediate-release oxycodone hydrochloride).
Panel members expressed concerns about Avridi’s efficacy and the potential for toxicity if patients who don’t see immediate relief take additional doses.
Only four opioid products, all of which are extended-release formulations, are approved with abuse-deterrent properties described in their labels. Purdue has received approval for three of those products: OxyContin (oxycodone), Targiniq (oxycodone and naloxone) and Hysingla (hydrocodone). The fourth product, Embeda (morphine sulphate and naltrexone), is manufactured by Pfizer. — Jonathon Shacat