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Study Underway to Examine the Planned Use of Voraxaze® with Methotrexate in CNS Lymphoma

Initial study results shared on American Academy of Neurology website

Initial data has been posted online from an investigator initiated pilot study exploring the planned use of Voraxaze® (glucarpidase) administered with repeated doses of methotrexate and rituximab in patients with central nervous system lymphoma (CNSL). Researchers at the Memorial Sloan Kettering Cancer Center planned to present their findings at an American Academy of Neurology (AAN) meeting in April which had to be cancelled. The abstract is available on the AAN website here.

High dose methotrexate, a standard treatment for CNSL, is regarded as an efficacious anti-tumor agent, but creates significant risk and burden for patients. Administration requires aggressive hydration and inpatient monitoring to prevent toxicity. Voraxaze® is known to result in a rapid and sustained reduction of serum methotrexate levels(ref) without crossing the blood brain barrier, suggesting there may be a role for Voraxaze® as a companion to methotrexate treatment.

“Chemotherapy can be one of the most daunting and demoralizing aspects of cancer treatment for patients and their families,” said Christon Hill, Vice President of Life Cycle Management at BTG Specialty Pharmaceuticals. “We often describe cancer patients as heroic in part because of the fight they must mount to sustain the effects of chemotherapy. We’re working together with top researchers to explore how routinely giving Voraxaze® in combination with methotrexate, might alleviate toxicity, manage the risk to patients and help them to complete therapy.”

In this pilot study, sponsored by Memorial Sloan Kettering Cancer Center in collaboration with the University of Alabama at Birmingham, adult patients with isolated CNSL are treated with rituximab and methotrexate 3 g/m2 or 6 g/m2 administered for eight cycles. Voraxaze® is given 24 hours following start of each methotrexate infusion. Methotrexate concentrations are monitored in serum and cerebrospinal fluid.

Based on the first five patients in the study having received a combined total of 24 doses of methotrexate, researchers shared initial findings that administration of Voraxaze® 24 hours after methotrexate results in repeated and consistent rapid reduction of serum methotrexate levels. In patients analyzed to date, methotrexate levels in the cerebrospinal fluid remain therapeutic and clinical response is seen.

Enrollment in the study is ongoing. For more information about the study, or to contact an investigator about participation, please visit https://clinicaltrials.gov/ct2/show/NCT03684980

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Indication and Limitations of Use

• Voraxaze® is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function

• Limitations of Use: Voraxaze® is not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Serious Hypersensitivity Reactions

• Serious hypersensitivity reactions, including anaphylactic reactions, may occur. Serious hypersensitivity reactions occurred in less than 1% of patients

Monitoring Methotrexate Concentration/Interference with Assay

• Methotrexate concentrations within 48 hours following Voraxaze® administration can only be reliably measured by a chromatographic method due to interference from metabolites. Measurement of methotrexate concentrations within 48 hours of Voraxaze® administration using immunoassays results in an overestimation of the methotrexate concentration

ADVERSE REACTIONS

• In clinical trials, the most common related adverse events (occurring in >1% of patients) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache.

DRUG INTERACTIONS

• Voraxaze® can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended, and may also reduce the concentrations other folate analogs or folate analog metabolic inhibitors.