Regulatory Decision Summary for Belbuca

Belbuca is an oral transmucosal formulation of buprenorphine, a synthetic long-acting partial agonist opioid.

Using the enriched enrollment random withdrawal (EERW) design, the efficacy of Belbuca was shown in two pivotal studies, one study in opioid naïve patients with chronic low back pain (CLBP) and one study in opioid experienced patients also with CLBP. The respective absolute effect sizes (pain score differences between Belbuca and placebo on an 11 point Numerical Rating Scale) were -0.67 and -0.98.

No unexpected treatment emergent adverse events (TEAEs) occurred during any of the phase I, II or III studies that were submitted. The TEAEs seen with BELBUCA in clinical studies were similar to those observed with other opioid analgesics (nausea, vomiting, constipation and somnolence).

The study submitted to assess the effect of buprenorphine on QT interval could not be considered as the patients in that study were concomitantly administered naltrexone (naltrexone might correct the effect of buprenorphine); the sponsor made a commitment to conduct a thorough QT study with Belbuca.

Belbuca is administered through the oral mucosa and pharmacokinetics has shown that buprenorphine was absorbed more rapidly, and to a greater extend, in subjects with mucositis. To mitigate the risk of overdose, the use of Belbuca in patients with known or suspected oral mucositis is contraindicated. This mitigation strategy was considered acceptable as, in Canada, there are alternative formulations of buprenorphine that can be given by different routes of administration.

Overall, the benefit-harm-uncertainty profile of Belbuca in the treatment of chronic pain is considered favorable for all proposed strengths (75µg, 150µg, 300µg, 450µg, 600µg, 750µg, and 900µg)