Subdermal Buprenorphine Implant Poised to Join Fight Against Painkiller Epidemic

FDA approval decision expected by May 27

As U.S. lawmakers search for ways to stop the current epidemic of heroin and painkiller abuse, two pharma companies––Titan Pharmaceuticals of San Francisco and Braeburn Pharmaceuticals of Princeton, New Jersey––have joined forces to develop a matchstick-sized implant that market analysts expect will be approved in May, according to a Reuters report. The product, known as Probuphine, is a six-month subdermal buprenorphine implant for the long-term maintenance treatment of opioid addiction. Implanted into the arm, the product is designed to be less vulnerable to abuse or illicit resale than the oral drugs that are currently used to treat opioid addiction.

Probuphine was developed using Titan’s ProNeura platform technology, which consists of a small rod made from a mixture of ethylene-vinyl acetate and a drug substance. The resulting product is a solid matrix that is placed subdermally, normally in the inner part of the upper arm, during a simple office procedure, and is removed in a similar manner at the end of treatment. The drug substance is released continuously through the process of dissolution, resulting in a stable, nonfluctuating blood level similar to that seen with intravenous administration.

In January 2016, the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) reviewed the new drug application for Probuphine and voted 12 to 5 in favor of approval. The panel expressed concern, however, about possible complications from insertion and removal of the inch-long implant. Trial data also showed that some users still needed oral buprenorphine.

If cleared by the FDA, Probuphine would be the first marketed product to provide maintenance treatment of opioid addiction continuously for six months after a single procedure. The agency’s approval decision is expected by May 27.

Phase 3 trial data supporting the efficacy of Probuphine were presented on April 15 at the annual conference of the American Society of Addiction Medicine. The findings indicated that subjects who were clinically stable on sublingual buprenorphine at a dosage of 8 mg or less per day maintained stability when transferred to Probuphine. The results also showed that subjects switched to Probuphine were more likely to remain free from illicit opioids throughout the six-month study period compared with the subjects who remained on sublingual buprenorphine (86% vs. 72%, respectively). Thus, Probuphine was shown to be noninferior to sublingual buprenorphine (the trial’s primary endpoint).

Other companies could also enter the addiction-prevention market. Indivior Plc, spun off from the Reckitt Benckiser Group, has a buprenorphine injection in late-stage development. North Carolina-based BioDelivery Sciences International, which currently sells a buprenorphine film, is also working on an injectable formulation.

Sources: Reuters; April 29, 2016; and Titan Pharmaceuticals; April 15, 2016.