Regulatory Decision Summary for Besponsa

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:


Medicinal ingredient(s):

Inotuzumab ozogamicin

Therapeutic area:

Antineoplastic agent

Type of submission:

New Drug Submission

Control number:

What was the purpose of this submission?


The purpose of this new drug submission (NDS) was to seek the authorization of Besponsa (inotuzumab ozogamicin) for use in adult patients with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.


Why was the decision issued?


The Sponsor provided a pivotal, multinational, open-label, randomized, phase III study of Besponsa (inotuzumab ozogamicin) compared to a defined investigators choice of chemotherapy in adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL).

Besponsa treatment demonstrated a clinically meaningful and statistically significant improvement in hematological remission rate (complete remission/incomplete hematologic recovery [CR/CRi]) as compared to the control arm (81% versus 32%). Additionally, the CR/CRi was supported by the achievement of a durable response and minimal residual disease (MRD) negativity that favored Besponsa treatment over the control arm. Notably, 48% of the patients in the Besponsa arm proceeded to potentially lifesaving hematopoietic stem cell transplant (HSCT) as compared to approximately 22% of the patients in the control arm. Besponsa treatment also resulted in a trending 1 month overall survival (OS) benefit favouring the Besponsa arm as compared to the control (7.7 versus 6.7 months), which did not meet the pre-specified statistical significance. Very likely, OS was confounded by a number of issues including:

  1. patients that proceeded to potentially life-saving HSCT,
  2. increased post HSCT non-relapse mortality in the Besponsa arm, and
  3. the high use of post-study induction therapies in patients in the control arm as compared to the Besponsa arm.

The safety profile of Besponsa in relapsed or refractory patients with B-cell precursor ALL has been characterized based on the pivotal and supportive clinical trial involving more than 200 patients with CD22-positive B-cell precursor ALL. The identified significant safety risks are hepatotoxicity and hematologic toxicity. Other important toxicities include cardiovascular (QT prolongation) and gastrointestinal toxicity. These toxicities, although significant, were:

  1. consistent between the pivotal and supportive study;
  2. clearly highlighted in the Adverse Reactions table and the Warnings and Precautions section of the Product Monograph (PM); and
  3. generally manageable, as demonstrated in the pivotal trial, by dose interruption, dose reduction, dose discontinuation and/or standard medical practice.

These mitigation strategies are clearly outlined in the PM. Additionally, a Serious Warnings and Precautions Box has been added to the PM to highlight the more severe, fatal and or life-threatening safety risks including: post-HSCT non-relapse mortality, hepatotoxicity (including venoocclusive disease), myelosuppression/cytopenia (including infections and hemorrhagic events), tumour lysis syndrome, infusion-related reactions and QT prolongation. Finally, given the significant hepatotoxicity observed in patients treated with Besponsa, the Sponsor has committed to conducting two additional clinical trials. One trial will evaluate two dose levels of Besponsa in patients at risk for hepatotoxicity and another will evaluate the toxicity of Besponsa in patients after HSCT.

Given the grim prognosis (3- to 6-month survival) and limited medical options for relapsed or refractory B-cell precursor ALL patients, at this time, HSCT is the only viable option for a patient to have a chance at a relatively longer term survival. To this end, Besponsa treatment helped more patients achieve a durable CR/CRi with MRD negativity, which helped more patients to proceed onto potentially lifesaving HSCT. The efficacy was coupled with a toxicity profile that was considered tolerable and manageable. As such, the benefit risk is considered positive under the proposed conditions of use.

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.