About 80% of the patients were adequately treated with four implants, but in some patients, a fifth rod or supplemental treatment with sublingual buprenorphine was needed. Completion rates were lower among those on placebo (31% and 26%, vs. 64% and 66%, respectively). In the two studies, the most common implant site–related adverse events included pruritus, pain, erythema, edema, and hematoma.
The company’s Risk Evaluation and Mitigation Strategy (REMS) includes plans for restricted distribution, a specialty pharmacy only, and a training-certification program for health care providers who implant the rods. (The FDA requires a REMS for a drug when it determines that a risk management strategies beyond the label are needed to ensure the benefits of a drug outweigh its risks.) Both the panel and the FDA reviewers said the REMS needs to be improved.
When asked about the panel’s recommendation, Dr. Robert L DuPont said in an interview that it is a major development in medication-assisted treatment of opiate dependence in light of problems with diversion and nonmedical use of buprenorphine. "This novel dosing strategy removes the risk of diversion in a large population of drug abusing patients that poses a high risk of diversion and misuse," said Dr. DuPont, the first director of the National Institute on Drug Abuse.
"The development of abuse-resistant formulations of controlled substances is one of the best new ideas to turn back the major epidemic of prescription drug abuse."
If approved, the panel recommended that other potential problems with the device should be monitored closely, including removal of implants by nonmedical personnel for diversion (which was not seen in the studies) and the risk of long-term exposure to the components if they are not removed. The panel urged study of whether implants can be inserted in previous implant sites.
Buprenorphine can be administered in an office setting as opposed to a methadone clinic. The currently marketed buprenorphine products are Subutex and Suboxone (buprenorphine with naloxone), both available in generic formulations; and a sublingual formulation approved in 2010. In 2012, 10.7 million prescriptions were dispensed for buprenorphine products for an estimated 1 million patients, mostly the buprenorphine/naloxone combination, according to the FDA. Between January 2003 and December 2012, an estimated 40 million buprenorphine prescriptions were written. The top three categories of prescribers were general practitioners/family physicians/doctors of osteopathy (one category), psychiatrists, and internists.
If approved, the manufacturer plans to market it as Probuphine. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist might be given a waiver, but not at this meeting.