The FDA agreed to review the denial of Probuphine, a subdermal implant which delivers the medicine buprenorphine to patients being treated for opioid addiction. Probuphine was previously denied approval because of concerns of the drug’s effect over time, its absorption rate and the training of doctors who have to add and remove the implant every six months.
Fear over Probuphine’s effectiveness stemmed from the drug’s lack of ability to block the effects of opioids taken by the user while on separate medication. The argument against this claim is the fact that Probuphine’s primary ingredient, buprenorphine, is not used for blocking the effects of opioids, but rather tries to suppress an opioid’s withdrawal symptoms.
As with any subdermal implant, the absorption rate of the drug will vary depending on the patient. The FDA worries that the amount of the drug received by the body over the implant’s six month lifespan will be too great and thus be dangerous.
The lack of doctor buy-in stems from Probuphine’s newness. Directions for inserting the implant are no different from those for inserting an IV, but because the implant is new to the market, the FDA is concerned that doctors will be hesitant to participate.
Titan Pharmaceutical’s Executive Vice President and Chief Development Officer Kate Beebe said in a company press release, “We are pleased that the FDA has accepted for review the resubmission of the NDA for Probuphine, and will be working with the agency and Braeburn to achieve our goal of offering the first product on the market to provide maintenance treatment of opioid addiction continuously for six months following a single treatment.”
Probuphine is a small, stick-shaped implant, usually located in the arm, and aims to make the application of buprenorphine easier by continually giving doses of the drug automatically for a period of six months. It is currently offered as a one-time dose via a dissolvable strip under the tongue. Using an implant eliminates some of the risks associated with taking pills. The medicine cannot be stolen or misused; a dose is never missed; if a patient has a job that involves travel, especially overseas, they don’t have to remember their medicine; and patients who live with small children do not have to worry about unintentional poisoning from the dissolvable tablet.
Results of a 24-week, double-blind study showed patients who used the Probuphine implant tested negative for illicit opioids significantly less often than those who had placebo implants. Forty percent of patients using the active implant showed no use of illicit drugs in weeks 1-16 of the study. This is compared to only a 28.3 percent average in the placebo group. Those who received the drug also showed fewer withdrawal symptoms, fewer cravings and a greater improvement on the Clinician Global Impressions Severity ratings of opioid dependence.
Dr. Frank Vocci, co-principal investigator, negotiated with the FDA to approve the study as a response to Probuphine’s denial and is prepared to conduct further studies on the drug’s impact should approval be given.
In January of 2016, after reviewing the newest data, a team of medical experts voted 12 to 5 to recommend Probuphine’s approval. The panel of doctors concluded that the benefits of a subdermal implant of buprenorphine outweighed its potential dangers. Maryland Department of Health Psychiatrist Dr. Thomas Grieger, a member of the panel who voted for approval, told The New York Times, “There is not evidence of significant risk using this agent, but there is evidence of significant benefit.” His opinion was corroborated by fellow panelist Dr. David Prickar, adjunct professor of psychiatry at Johns Hopkins Medical School. “I think this will save some folks’ lives,” he said. “From a safety point of view I think we’re in good shape.”
History shows the FDA follows the advice of its experts 74 percent of the time, which is good news for the future of Probuphine. The final decision on whether or not to approve Probuphine is expected in February of 2016.