New economic analysis of Voraxaze® (glucarpidase) in patients with delayed methotrexate

Model simulation shows cost of timely Voraxaze® use is offset by shorter hospital stays and associated with substantially improved clinical outcomes

West Conshohocken, PA, March 15, 2023 (GLOBE NEWSWIRE) -- BTG Pharmaceuticals, a SERB company, today announces the publication of an economic simulation assessing the value of Voraxaze® (glucarpidase) for treating adult patients in the United States who experience delayed methotrexate elimination due to impaired renal function. The analysis was published in the peer-reviewed journal ClinicoEconomics and Outcomes Research (available via open access here)i.

Researchers built an economic model comparing the current standard of care, including delayed glucarpidase treatment or hemodialysis, with a proposed practice of treating all eligible patients with Voraxaze® within 48-60 hours from the start of the high dose methotrexate (HDMTX) infusion, in accordance with current consensus guidelines.

Study co-author Jaya Kala, MD, Onco-nephrologist, Houston, TX, said: “In addition to economic benefits, the analysis shows that timely use of glucarpidase could lead to substantial improvements in patient care. The model showed that proposed practice allowed more patients to complete their cancer therapy, shortened hospital stays, and reduced the need for hemodialysis and its associated risks.”

Simulations based on the model showed that for each patient with delayed elimination of HDMTX due to impaired renal function, timely treatment with Voraxaze® resulted in cost savings compared with hemodialysis or delayed Voraxaze® treatment. Treatment with Voraxaze® had an incremental cost versus standard of care alone but was associated with shorter hospital stays and substantially improved clinical outcomes.

The simulation analysis found that timely treatment of all eligible patients with Voraxaze® (within 48-60 hours from the start of HDMTX infusion) was associated with:

  • a 12% increase in cost per patient, offset by decreased hospital costs.
  • Increased patient survival rates.
  • Decreased number of patients requiring hemodialysis.
  • Increased opportunity for HDMTX rechallenge.
  • Reduced hospital & ICU length of stay.

Study co-author Rebecca Nelson, PharmD, BCOP, malignant hematology clinical pharmacy supervisor, Moffitt Cancer Center, said: “Along with the clinical and economic impact of timely glucarpidase intervention, this article also discusses rechallenging patients with HDMTX. This is an important consideration for resuming patients’ care after experiencing this potentially life-threatening event of delayed methotrexate elimination with acute kidney injury during their treatment. Intervening with glucarpidase timely, where indicated, can increase the opportunity to rechallenge patients with HDMTX.”

The study also outlines hypothetical practical scenarios for large US institutions. One scenario describes an institution that treats 50 adult patients with HDMTX per year, one of whom receives a delayed administration of Voraxaze® (at 72 hours). According to the model, an institution such as this could save over $70,000 if they shift practice to the timely administration of Voraxaze®.

“This study shows that even with conservative assumptions, using Voraxaze as recommended in the guidelines delivers benefits for both patients and hospitals,” said Thomas Kolaras, Chief Commercial Officer for BTG Pharmaceuticals. “If hospitals also take into account reimbursement rates – which are not included in this analysis – as well as other costs associated with the standard of care, hemodialysis, and monitoring, the economic rationale is even clearer regarding earlier intervention with Voraxaze.”

About the Study

Researchers developed a decision tree model to reflect the average number of patients treated with HDMTX at a large US institution in one year. The model, informed by real-world Medicare claims data, conservatively estimates the costs and clinical outcomes for the treatment practice recommended by consensus guidelines where eligible patients are treated with Voraxaze® within 60 hours, as compared with treatment with standard of care alone or in conjunction with delayed glucarpidase or hemodyialysis. The model also estimated the three-year cancer survival associated with the ability to resume treatment with HDMTX after treatment for delayed methotrexate elimination.

This article can is available via open access here:

About Methotrexate Toxicity

Methotrexate is a potent anticancer agent used in high doses (>500 mg/m2) to treat osteosarcoma, lymphomas, and lymphoblastic leukemia. Because methotrexate is primarily cleared by the kidneys, high doses can impair kidney function and lead to delayed methotrexate elimination. Exposure to elevated concentrations of methotrexate for minutes to hours may lead to acute renal toxicity and other serious systemic adverse reactions. In clinical studies, patients treated with Voraxaze® experience rapid and sustained reductions in plasma MTX concentrations. ii, iii

About BTG Pharmaceuticals

BTG, a SERB company, is dedicated to helping healthcare providers treat patients with critical conditions, focusing on emergency care and rare diseases. For over 30 years we have helped treat complex and life-threatening conditions; supporting clinicians, healthcare systems and governments while offering hope to patients and their families. As a fully integrated company, we have the experience and capabilities to acquire, develop, and manufacture our medicines to the highest standards, and make them available worldwide through our secure supply chain.  For more information visit:

Voraxaze® US 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

Please see full Prescribing Information.


  1. Kala J, Nelson R, Drudge C, Zhou A, Ward S, Bourque M. Glucarpidase for Treating Adults with Delayed Methotrexate Elimination Due to Impaired Renal Function: An Economic Simulation Analysis. Clinicoecon Outcomes Res. 2023;15:165-179
  2. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010;28(25):3979-3986.
  3. 2013 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT). Clin Toxicol. 2013;51(7):575-724.


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