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Initial study results show feasibility of outpatient methotrexate administration with planned-use Voraxaze® (glucarpidase) during COVID-19 pandemic

BTG Specialty Pharmaceuticals highlights study inspired by COVID-19 pandemic conditions, presented at Society for NeuroOncology annual conference

Initial data from two cohorts of an investigator initiated study exploring the planned use of Voraxaze® (glucarpidase) following high dose methotrexate (MTX) administered in patients with central nervous system lymphoma (CNSL) are available on the Society for NeuroOncology (SNO) website (abstract COVD-23, abstract CTNI-61). Researchers at Memorial Sloan Kettering Cancer Center will present both abstracts at the SNO virtual annual meeting on November 19, 2020.

An ongoing arm of the study inspired by the difficult circumstances created by the COVID-19 pandemic is exploring the planned use of Voraxaze® to enable high dose MTX treatment of CNSL on an outpatient basis. The pandemic can put pressure on hospital resources and elderly or at-risk patients may be less willing to visit a hospital for cancer treatment. Rather than put these procedures on hold, patients in this study were able to continue their treatment in a community outpatient setting without having to be admitted to a hospital.

“This study explores whether a protocol using glucarpidase following high dose methotrexate can enable outpatient treatment in a community setting,” said Dr. Lauren Schaff, principal investigator for the study. “The initial findings are encouraging, as none of the enrolled patients required hospital admission, and all patients treated with this protocol requested to continue treatment in the outpatient setting. This protocol could be particularly valuable during the ongoing COVID-19 pandemic as patients may be reluctant to travel to hospitals.”

High dose MTX, 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 produce a rapid and sustained reduction of serum methotrexate levels without crossing the blood brain barrier, suggesting that Voraxaze® as a companion to methotrexate treatment could reduce hospital stays or even allow outpatient treatment of CNSL.

Adult patients with isolated CNSL were administered MTX 3.5 g/m2 in the outpatient setting with hydration. Patients returned 24 hours later for Voraxaze® 2000u and additional hydration. MTX levels were measured 24 and 48 hours following MTX administration.

Seven outpatient high dose MTX treatments were administered to a total of three patients. In all cases, MTX levels were reduced to < 100 nmol/L at 48 hours. Three treatments resulted in grade 1 elevation of the liver enzymes AST/ALT (two patients). One treatment resulted in a grade 2 creatinine increase. Creatinine returned to baseline following additional outpatient hydration. No patients required hospital admission.

In a separate abstract to be presented at the SNO meeting, the investigators will share initial data from another study cohort exploring repeated use of Voraxaze® following high dose MTX in patients with CNSL. Data on 50 doses of MTX administered to 12 adult patients with isolated CNSL showed that administration of low-dose Voraxaze® 24 hours after MTX 3-8 g/m2 resulted in a reproducible rapid reduction in serum MTX levels in non-renally impaired patients. MTX levels in the cerebrospinal fluid remained therapeutic and the clinical response appeared to be as expected from MTX-based therapy.

Investigators are currently enrolling to a larger study of planned-use Voraxaze® for repeated doses of outpatient HD-MTX. For more information about the study, or to contact an investigator about participation, please visit https://clinicaltrials.gov/ct2/show/NCT03684980

For more information about BTG Specialty Pharmaceuticals support for Investigator Initiated Studies, please visit https://btgsp.com/research

About BTG Specialty Pharmaceuticals

BTG Specialty Pharmaceuticals, a division of Boston Scientific, provides rescue medicines typically used in emergency rooms and intensive care units to treat patients for whom there are limited treatment options. We are dedicated to the development, manufacture, and commercialization of quality medicines that make a real difference to patients and their families. Our current portfolio of antidotes counteracts certain snake venoms and the toxicity associated with some heart and cancer medications. To learn more, please visit: btgsp.com.

For further information contact:
Chris Sampson, Corporate Communications Director
chris.sampson@btgsp.com; Mobile: +44 (0)7773 251 178

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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.