WHAT IS THE CADTH REIMBURSEMENT RECOMMENDATION FOR RYLAZE?: CADTH recommends that Rylaze be reimbursed by public drug plans 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 derived asparaginase if certain conditions are met. WHICH PATIENTS ARE ELIGIBLE FOR COVERAGE? Rylaze (crisantaspase recombinant) should only be covered to treat patients who have ALL or LBL with documented hypersensitivity to (or silent inactivation of) an derived asparaginase. WHAT ARE THE CONDITIONS FOR REIMBURSEMENT? Rylaze should only be reimbursed as part of a multicomponent treatment regimen to replace pegylated derived asparaginases (pegaspargase), following hypersensitivity or silent inactivation of the derived asparaginase. Rylaze should be prescribed by clinicians with expertise in the management of ALL or LBL, and the cost of Rylaze should be reduced. WHY DID CADTH MAKE THIS RECOMMENDATION? A single-arm trial showed that children and adults with ALL or LBL and hypersensitivity or silent inactivation to derived asparaginase treated with 1 course (6 doses) of crisantaspase recombinant intramuscularly (IM) achieved adequate values of asparaginase activity, with adverse events (AEs) that were considered manageable and within the expected frequency of harms observed in patients with ALL or LBL. Rylaze meets an important need in the Canadian landscape due to scarcity of other options in patients with hypersensitivity or silent inactivation to asparaginase. Based on CADTH’s assessment, there is insufficient health economic evidence to determine whether Rylaze represents good value to the health care system at the public list price compared with other -derived asparaginase (EDA) treatments. Based on public list prices, Rylaze is estimated to cost the public drug plans approximately $2.7 million over the next 3 years if the comparator EDA remains available and $26.8 million if it does not.

ADDITIONAL INFORMATION

WHAT ARE ALL AND LBL? Both ALL and LBL are types of cancers of the blood and bone marrow. ALL affects a type of white blood cell called lymphocytes and LBL affects immature white blood cells (lymphoblasts). Symptoms are nonspecific and may include fatigue, pain, shortness of breath, and other symptoms. Both types of cancers are more common in children than adults and are common types of childhood cancer. Of those who receive asparaginase treatment, approximately 10% to 30% have documented hypersensitivity to asparaginase derived from and need other treatment options. UNMET NEEDS IN ALL AND LBL: Asparaginase is an essential part of treating patients with ALL and LBL. As asparaginase is made from small parts of a bacteria called , some patients can produce antibodies against the drug, which can reduce the activity of the asparaginase and affect patients’ clinical evolutions and outcomes. When this happens, doctors call it hypersensitivity (or silent inactivation when there are no symptoms); hypersensitivity prompts the need for other treatment options. There is an important need in the Canadian landscape due to issues of scarcity of other options in patients with hypersensitivity or silent inactivation to derived asparaginase. HOW MUCH DOES RYLAZE COST? Treatment with Rylaze is expected to cost approximately $24,022 per 2-week course in the pediatric and young adult population and $43,676 per 2-week course for older adults.