Regulatory Decision Summary for Mylotarg

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.


Product type:

Drug

Medicinal ingredient(s):

gemtuzumab ozogamacin

Therapeutic area:

Anti-neoplastic Agent

Type of submission:

New Drug Submission

Control number:

223091
What was the purpose of this submission?

 

The purpose of this New Drug Submission (NDS) was to seek market authorization of Mylotarg (gemtuzumab ozogamicin) in combination with chemotherapy (daunorubicin and cytarabine) for treatment of patients with previously untreated, de novo AML. After evaluation of the submitted data package, Health Canada authorized the following indications: Mylotarg is indicated for combination therapy with daunorubicin and cytarabine for the treatment of adult patients with previously untreated, de novo CD33-positive acute myeloid leukemia, except acute promyelocytic leukemia.

 

Why was the decision issued?

 

Authorization of was primarily based on the results from the pivotal Phase 3 study (n=271). This was a randomized, open-labelled, parallel, two arm study, comparing the efficacy and safety of adult patients with previously untreated de novo acute myeloid leukemia treated with Mylotarg in combination with chemotherapy (daunorubicin and cytarabine, [Mylotarg arm, n=135]) to chemotherapy alone (control arm, n=136). Mylotarg was administered on Days 1, 4, and 7 during induction therapy and on Day 1 during consolidation therapy.

The primary efficacy endpoint of the pivotal study was event-free survival (EFS). EFS represented the time during which patients did not experience treatment failure, relapse of disease or death. Patients who received Mylotarg in combination with chemotherapy experienced a longer median EFS compared to patients who received chemotherapy alone, 13.6 months versus 8.5 months. The addition of Mylotarg to chemotherapy resulted in a, clinically meaningful, 34% reduction in the risk of treatment failure, relapse of disease or death. In addition, patients who received Mylotarg in combination with chemotherapy experienced a longer median overall survival compared to patients who received chemotherapy alone, 27.5 months versus 21.8 months. The addition of Mylotarg to chemotherapy resulted in a 19% reduction in the risk of death.

The identified serious risks with gemtuzumab ozogamacin (GO) include, hepatotoxicity (including veno-occlusive disease [VOD]), myelosuppresion/cytopenias (including infections and haemorrhage), tumour lysis syndrome (TLS) and infusion-related reactions. With respect these risks, fatal and/or life-threatening events have been observed with GO. These risks have been identified in a Serious Warnings and Precautions box of the Product Monograph (PM). The occurrence of early deaths (within 28 or 30 days of last dose of any study treatment) was similar between treatment arms. Treatment-related mortality was slightly higher for patients in the GO arm, 5.3% versus 3.6% in the control arm. The increase was driven by deaths due to haemorrhage and hepatotoxicity (VOD). Thrombocytopenia, hepatotoxicity (VOD), haemorrhage and infection were the most common reasons that lead to treatment discontinuation. Patients treated with GO experienced higher incidences of thrombocytopenia, prolonged thrombocytopenia, and higher number of platelet transfusions. Risk mitigation strategies, including patient monitoring, dose modifications and recommendations for permanently discontinuing GO treatment have been outlined in the product monograph (PM).

Overall, the risks associated with GO are appropriately captured in the PM and are considered tolerable and manageable.

A Notice of Compliance (NOC) was recommended based on the benefit-risk profile in the indicated population.

For more information on Health Canadas decision, please view the Summary Basis of Decision.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.