Regulatory Decision Summary for Rylaze

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):

crisantaspase recombinant

Therapeutic area:

Antineoplastic Agent

Type of submission:

New Drug Submission

Control number:

257092
What was the purpose of this submission?

 

The purpose of this new drug submission was to seek market authorization for Rylaze (crisantaspase recombinant), for use in the treatment of adult and pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma who have developed hypersensitivity to E. coli-derived asparaginase.

After evaluation of the submitted data package, Health Canada authorized Rylaze for the following indication:

Rylaze (crisantaspase recombinant) is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 year or older who have developed hypersensitivity to E. coli-derived asparaginase.

 

Why was the decision issued?

 

The market authorization of Rylaze was based on the results of a pivotal Phase 2/3, open-label, multicenter trial, in adult and pediatric patients 1 year or older with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) who had developed hypersensitivity to E. coli-derived asparaginase (pegaspargase). Patients received Rylaze at one of three dosages, administered intramuscularly (IM) on Monday, Wednesday and Friday, for a total of 6 doses to replace each dose of pegaspargase remaining on their treatment plan. Rylaze was administered as a component of a multi-agent chemotherapeutic regimen.

The determination of efficacy was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) at a level of ≥ 0.1 U/mL. Although patients achieved a response rate of 89.6% at the last 72-hour assessment during the first course of treatment, the lower bound of the 95% confidence interval (CI) of the response rate did not reach 90%, as was predefined to represent achievement of the primary endpoint of the study. However, the results of modelling and simulations showed that for a dosage of 25 mg/m2 administered IM on a Monday and Wednesday and 50 mg/m2 administered IM on a Friday, the proportion of patients expected to maintain NSAA ≥ 0.1 U/mL was 93.0% (95% CI: 91.8%, 94.1%) at 48 hours after a dose of Rylaze, and 91.0% (95% CI: 89.7%, 92.2%) at 72 hours after a dose of Rylaze. Overall, these results are considered clinically meaningful in the indicated patient population.

The safety profile of Rylaze is generally consistent with that of other asparaginase class products. Adverse reactions requiring monitoring and/or dosage adjustment include hypersensitivity, hepatotoxicity, pancreatitis, thrombosis, hemorrhage, and hyperglycemia. The risks associated with Rylaze can be effectively managed and important safety information has been captured in the Rylaze Product Monograph.

Overall, Rylaze provides an effective treatment option with the potential to allow patients to continue receiving asparaginase as part of their treatment for ALL or LBL in the event they can no longer receive pegaspargase due to development of hypersensitivity. When administered at the authorized dosage as a component of multi-agent chemotherapy, Rylaze is expected to maintain asparaginase activity at clinically meaningful levels in a high percentage of patients. The risks associated with Rylaze can be effectively managed in the post-market setting. The benefit/risk profile of Rylaze is considered favourable for the authorized indication.

The sponsor is required to submit additional modelling data to assess efficacy and safety in patients younger than 1 year of age. Additionally, the sponsor is required to provide an assessment of immunogenicity in all patients enrolled in the pivotal trial.

 

Decision issued

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