Panel recommends FDA approve implant to treat opiate addiction

An advisory committee recommended Tuesday that the Food and Drug Administration (FDA) approve an implant designed to reduce addicts’ cravings for heroin or prescription painkillers.

The implant, probuphine, provides a steady dose of buprenorphine, which has been shown to ease withdrawal symptoms, decrease cravings and cut the risk of relapse. Buprenorphine is currently available only as a pill or dissolvable film that’s placed under the tongue. Although it can be life-saving, it carries major risks: some addicts sell their supplies to get money for other drugs.

Probuphine’s manufacturer, New Jersey-based Braeburn Pharmaceuticals, says the implant eliminates that risk. The FDA typically follows committees’ advice.

Probuphine’s development comes at a time when addiction to opiates — which include illegal drugs such as heroin, as well as prescription painkillers such as morphine and OxyContin — has been called an epidemic.

The death rate from drug overdoses more than doubled from 1999 to 2013, according to the Centers for Disease Control and Prevention. Drug overdoses now kill 44,000 Americans a year – more than car accidents.

At the advisory panel’s meeting Tuesday, several witnesses described how opiate addiction has harmed them or their families. Two fathers described how their sons died from drug overdoses, and both asked the committee to recommend approving probuphine.

Medications to treat addiction are strictly regulated.

Methadone is available only at specialized clinics, where patients typically must go every day to receive a dose. Buprenorphine is considered safer than methadone because it’s less likely to cause an overdose. Patients can receive buprenorphine at a doctor’s office, but physicians prescribing the drug must be certified to dispense it and are only allowed to treat 100 patients at a time.

Like all pills, buprenorphine can be accidentally swallowed by children. About 1 million people took buprenorphine in 2012, according to the FDA.

The White House has recommended expanding the use of medications that treat opiate addiction. Addicts who are given such “medication-assisted treatment” cut their risk of death in half, according to the Substance Abuse and Mental Health Services Administration. The medications also halve a person’s risk of becoming infected with HIV, the virus that causes AIDS.

Probuphine works like a contraceptive implant, such as Norplant. Four implanted rods, each smaller than a match stick, provide a steady amount of medication for up to 6 months. The FDA is considering approving it for a specific population: “stable” patients who are already taking the dissolvable buprenorphine film at a low dose. The committee voted 12-5 in favor of probuphine.

“I think this will save some folks’ lives,” said advisory committee member David Pickar, an adjunct professor of psychiatry at Johns Hopkins Medical School in Baltimore.

Doctors who want to prescribe probuphine would have to refer patients to providers trained to implant medical devices, or undergo training to learn how to safely implant and remove it, said Behshad Sheldon, president and CEO of Braeburn Pharmaceuticals, who spoke at Tuesday’s advisory committee hearing.

Implanting probuphine takes 10 to 15 minutes and removing it takes about 20 minutes, said Steven Chavoustie, a physician involved in a clinical trial of the device.

Pharmacist Tracy Rupp urged the committee to reject probuphine, noting that its manufacturer presented only one clinical study showing the drug was effective.

In the study, doctors compared the use of probuphine implants and buprenorphine film, Sheldon said. Patients in the study were considered “stable” because they had been safely using the films. After 6 months, 85% of those given probuphine tested negative for illegal drugs, compared to 72% of those given the film.

The study had multiple flaws, said Rupp, director of public health policy initiatives at the National Center for Health Research, a nonpartisan group that analyzes health data.

Some missing urine tests were counted as negative, as if the patient had no drugs in their system. But Rupp noted that people addicted to opiates “often skip tests to avoid a positive test.” That could skew the results, Rupp said.

“It is disappointing that the advisory committee set such a low bar for safety and effectiveness,” Rupp said after the vote. “Is probuphine effective? We still don’t know because the study was poorly designed and missing data.”

Judith Kramer, the committee’s acting chairwoman, said she voted against recommending probuphine’s approval because doctors don’t yet know if it’s effective for more than 6 months. Many people who are addicted to opiates need to take medication for years, she added.

“We all desperately want something to be available” to treat opiate addiction, said Kramer, a professor emerita at Duke University in Durham, N.C. Yet she added: “I’m very concerned about the precedent this sets.”

Some addiction specialists say they’re concerned about probuphine’s safety.

Doctors don’t yet know how to safely transition patients from buprenorphine films to the implant, said pharmacist Tracy Rupp, director of public health policy initiatives at the National Center for Health Research, a nonpartisan group that analyzes health data.

Rupp, who recommended the committee reject probuphine, said it takes up to four weeks for the implant to provide the same level of medication provided by the film strips. That suggests patients will need to continue taking buprenorphine by mouth for the first few weeks after receiving the implant, Rupp said.

Rupp said she’s worried patients could relapse during that transition. “This is an unacceptable risk for stable patients,” Rupp said.

Rupp also said the study didn’t match the demographics of addicts in real life, noting 84% of the patients in the study were white. Jennifer Higgins, the committee’s acting consumer representative, said she would like the FDA to require studies in more diverse populations.

“This is not the real world of opioid addiction,” Rupp said. “Many of these patients will require treatment for years. We need long-term safety data from diverse populations. Patients will require a new incision every 6 months, creating an ongoing risk of harm due to bleeding and infectious complications.”