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?
In this Supplemental New Drug Submission (NDS), the sponsor is requesting to extend the market authorization for Imbruvica to include the treatment of patients with Waldenströms Macroglobulinemia (WM).
Why was the decision issued?
Waldenstroms Macroglobulinemia is a rare and incurable lymphoproliferative disease of B lymphocytes. Ibrutinib (the medicinal ingredient in Imbruvica) targets an aberrant signaling pathway found in approximately 90% of WM tumors which provides a rationale for its investigation in this disease.
The safety and efficacy of Imbruvica were evaluated in an open-label, multi-centre, single-arm trial of 63 previously treated patients with WM. Patients were treated with daily 420 mg/day oral Imbruvica. Patients achieved an overall response rate (ORR) of 87%, with 14% Very Good Partial responses, 55% Partial Responses, 18% Minor Responses. The median duration of ORR was not reached; analysis at the 18-month landmark showed that 86% of all responders remained alive and progression-free, representing a durable response. Of the 38 patients with low hemoglobin levels at baseline, a sustained improvement in hemoglobin was reported in 82%.
The most common treatment-emergent adverse events (TEAEs) in this study were diarrhea, neutropenia, thrombocytopenia, anemia, nausea, fatigue, muscle spasms, rash, epistaxis, sinusitis, and upper respiratory tract infection. Most TEAEs were low grade and adequately managed. Overall, the Imbruvica safety profile observed in WM patients was generally consistent with that already established from previous reviewed studies in the treatment of Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma patients. However, non-melanoma skin cancer was identified as a new risk associated with Imbruvica. Imbruvica has a tolerable safety profile for WM patients, and the updated product monograph provides recommendations to appropriately mitigate its associated risks.
The response rates achieved for WM patients following treatment with Imbruvica were high, durable, and clinically relevant, and a small single arm study in this rare disease was considered appropriate. With an acceptable and well characterized safety profile, Therapeutics Products Directorate (TPD) concluded the benefit-risk profile for Imbruvica in the treatment of patients with WM is positive.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.