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FDA Rejects Opioid-Dependence Drug Probuphine (Buprenorphine)
The FDA has issued a complete response letter (CRL) to the new drug application (NDA) for Probuphine (buprenorphine subdermal implant; Titan Pharmaceuticals) for the maintenance treatment of opioid dependence in adults.
The CRL states that the FDA cannot approve the application in its present form. The agency has requested additional data supporting the efficacy of Probuphine, including:
- The drug’s ability to provide opioid blockade of relevant doses of agonists
- The effect of higher doses of Probuphine, ideally doses more closely approximating the blood plasma levels associated with sublingual doses of buprenorphine (12 to 16 mg/day)
- Human-factors testing of the training associated with Probuphine’s insertion and removal
The CRL also includes recommendations regarding product labeling and the implementation of a risk evaluation and mitigation strategy (REMS).
Probuphine is an investigational subdermal implant designed to deliver continuous blood levels of buprenorphine for 6 months following a single treatment. Buprenorphine, an approved agent for the treatment of opioid dependence, is currently available in the form of daily-dosed sublingual tablets and film formulations, with reported 2011 sales of $1.3 billion in the U.S.
Probuphine consists of a small, solid implant made from a mixture of ethylene-vinyl acetate (EVA) and the drug substance (buprenorphine). The resulting construct is a solid matrix that is placed subdermally, normally in the upper arm, in a simple office procedure. The implant is removed at the end of the treatment period. Buprenorphine is released slowly and continuously through the process of dissolution, resulting in a steady rate of release.
Source: Titan Pharmaceuticals; April 30, 2013.