Regulatory Decision Summary for Sublocade
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
This New Drug Submission was filed to seek an indication for Sublocade for the treatment of moderate to severe opioid use disorder (OUD) in adults, as part of a complete treatment plan that includes counselling and psychosocial support. Upon review, the indication was modified to specify that patients should be clinically stabilized on a transmucosal buprenorphine-containing product. Sublocade is an extended-release, subcutaneous injection of buprenorphine.
OUD is defined as a neurobehavioural syndrome characterized by repeated, compulsive seeking/use of an opioid despite adverse social, psychological or physical consequences. In addition to pain-related indications, buprenorphine-containing products are also approved in Canada for the management of opioid dependence. Sublocade is currently approved in the United States (April 2018) for a similar indication as requested in the current application.
Why was the decision issued?
Patients with opioid use disorder (OUD) have physical and psychological addiction to the substance. Patients with OUD have a life centered on opioid consumption regardless of social, psychological, or physical consequences. Currently, one of the management strategies for the treatment of OUD is the use of buprenorphine products (substitution therapy) along with drug counselling and psychological support.
Buprenorphine is a partial agonist of µ-opioid receptor. Various formulations of buprenorphine are currently used for the treatment of patients addicted to opiate products with mixed rates of success. This submission was filed seeking an indication for Sublocade, a monthly, subcutaneous injection of buprenorphine in the management of patients with moderate to severe OUD in conjunction with drug counselling and psychological support.
To support the sought indication, the sponsor provided a single placebo-controlled trial of two doses of Sublocade, followed by an open-label safety study. Other supportive studies included clinical pharmacology trials, pooled analysis of pharmacokinetic data, a receptor occupation study, analysis of tamper-resistant properties of the product, and a controlled blockade study. During the development program, a total of 570 and 395 patients, respectively, received 6 and 12 monthly injections of Sublocade.
The single pivotal trial in this New Drug Submission showed that both 100 mg and 300 mg maintenance doses of Sublocade administered over 6 months were statistically significantly better than placebo. Clinical pharmacology data showed that steady-state plasma levels of buprenorphine were well above the minimum demonstrated in previous studies to be required for sufficient opioid receptor blockade. Open-label and other studies established safety and tolerability of Sublocade in patients with OUD for up to 12 injections.
Other safety topics of interest included QT-interval prolongation, teratogenicity, hepatic-related adverse events, injection site conditions, and use of Sublocade in pregnancy. All of these issues have been labelled properly and risks associated with such events can be mitigated with monitoring and data collection as outlined in the Risk Management Plan. At this time and with the currently available information, Benefit-Harm Uncertainty of Sublocade use in the management of patients with OUD is favourable.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.