Regulatory Decision Summary for Imbruvica
Review decision
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.
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What was the purpose of this submission?
This supplemental new drug submission (SNDS) was filed to add a new indication for Imbruvica for the treatment of patients with steroid dependent or refractory chronic Graft Versus Host Disease (cGVHD).
Why was the decision issued?
Efficacy of Imbruvica for the proposed indication was based on a single Phase 1b/2, open label, single arm trial (Study 1129) conducted in 42 subjects with steroid dependent or refractory chronic Graft Versus Host Disease (cGVHD). Assessment of safety was based on this study and was also supplemented by Imbruvica safety data from the pivotal trials supporting the other market authorized indications.
Treatment with Imbruvica 420 mg/day provided a best overall response rate (BORR) of 66.7%, including 21% of patients who displayed a complete response and 45% of patients who had a partial response. Based on current clinical treatment standards, a BORR of 25% or more is considered to be clinically meaningful in this disease setting. Therefore, although this was a small study, there was evidence of clinically meaningful efficacy of Imbruvica in patients with cGVHD.
The safety profile of Imbruvica in cGVHD patients in the pivotal trial was generally comparable to that described for Imbruvica in patients from other Imbruvica trials supporting other indications. The most common adverse events reported by the cGVHD patients were fatigue, bruising, diarrhea, muscle spasms, stomatitis, nausea, hemorrhage, and pneumonia, and the most frequent laboratory abnormalities were decreases in platelet and hemoglobin levels. No new safety signals were identified in the current submission.
Despite the small size of the pivotal trial provided in this submission, it is recognized that the high response rate in this very refractory clinical setting, along with a generally tolerable safety profile, provides a clinically meaningful benefit to those patients with steroid dependent or refractory cGVHD. The Product Monograph has been revised to reflect the efficacy and safety data to inform healthcare providers and patients.
Based on the data provided in the submission, the benefit-harm-uncertainty assessment is positive for Imbruvica for the treatment of patients with steroid dependent or refractory cGVHD.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.