Regulatory Decision Summary for Orencia
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?
The purpose of this submission was to seek authorization of Orencia (abatacept) for the prophylaxis of moderate to severe acute graft versus host disease (aGVHD) in unrelated-donor hematopoietic stem cell transplantation (HSCT) in patients 6 years of age and older.
After evaluation of the submitted data package, Health Canada authorized Orencia for the following indication:
- the prophylaxis of moderate to severe acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 6 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.
Orencia has already been authorized by Health Canada for the treatment of adult rheumatoid arthritis, juvenile idiopathic arthritis, and adult psoriatic arthritis.
Why was the decision issued?
Market authorization was based on the results of a main trial and a supportive study that used data from a Center for International Blood and Marrow Transplant Research.
In the main trial, two cohorts of patients were studied:
A randomized, double-blind, place-controlled study of patients who underwent an 8 of 8 Human Leukocyte Antigen (HLA)-matched HSCT who received Orencia (73 patients) or placebo (69 patients) in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX) (8 of 8 cohort); and
An open-label, single-arm study of 43 patients who underwent a 7 of 8 HLA-matched HSCT (7 of 8 cohort).
Compared to standard aGVHD prophylaxis regimen, the addition of Orencia to standard aGVHD prophylaxis regimen (CNI + MTX) had statistically significant improvement in moderate to severe GVHD free survival (GFS), overall survival (OS), disease free survival (DFS), and lower transplant related mortality (TRM) assessed at Day 180 post-transplantation for 8 of 8 cohort.
Due to the limitations of the exploratory analysis for the 7 of 8 single arm cohort, a retrospective study was conducted using real world data routinely collected into the Center of International Blood and Marrow Transplant Research (CIBMTR) database. This retrospective cohort study compared the overall survival (OS) with 180 days of follow-up post-HSCT in 7 of 8 HLA-matched patients treated with CNI + MTX + Orencia (ABA) without antithymocyte globulin (ATG) to those treated with CNI + MTX without ATG. The OS at day 180 was greater in the CNI + MTX + Orencia without ATG group compared to patients treated with background CNI + MTX without ATG (98% vs 75%).
The most common (10%) adverse reactions in the Orencia treated patients were anemia, hypertension, cytomegalovirus (CMV) reactivation/infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury. Higher number of infections, CMV and Epstein-Barr Virus (EBV) reactivation/infection, and post-transplant Lymphoproliferative Disorder (PTLD) were observed in patients who received Orencia for aGVHD prophylaxis during unrelated HSCT. PTLD was associated with EBV infection. Special details for monitoring and preventing CMV and EBV infection/reactivation are provide in the product monograph (PM).
The recommended dose of the Orencia is 10 mg/kg (maximum dose of 1,000 mg) as intravenous infusion over 60-minutes on the day before transplantation (Day -1), followed by administration on Day 5, 14, and 28 after transplantation. View the PM for details.
The overall benefit-risk assessment is considered favourable. A Notice of Compliance (NOC) is recommended.
Decision issued
Approved; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.