A Retrospective Study of Medicare Claim Data Shows Patients Treated with Voraxaze® had Shorter Hospitalizations and Lower Mortality

PHILADELPHIA, Feb. 14, 2019 /PRNewswire/ -- BTG plc (LSE: BTG), the global healthcare company, today announced the publication of data showing that cancer patients with presumed methotrexate toxicity treated with Voraxaze^® (glucarpidase) had shorter hospital stays, lower in-patient mortality, and lower 90-day mortality than those treated with conventional treatment.  The study, based on a retrospective review of Medicare claim data, was published in the journal ClinicoEconomics and Outcomes Research.

"This is the first comparison of patient outcomes associated with Voraxaze^® relative to outcomes experienced by similar patients not treated with Voraxaze^®," said Christon Hill, Vice President of R&D for BTG Pharmaceuticals. "Together with existing clinical data and the inclusion of Voraxaze^® in consensus treatment guidelines, this review of Medicare patient data adds useful evidence for physicians and payers treating cancer patients."

Researchers used 2010-2017 Medicare claim data to identify patients with select lymphomas or leukemia, inpatient chemotherapy, and treatment with Voraxaze^®.  Hospital length of stay, mortality, and readmission rates were compared between these patients and those treated with alternative therapies.  Researchers conducted inverse probability treatment weighting using propensity scores to control for between-group differences in patient characteristics and to make the groups comparable.  An exploratory analysis also compared outcomes between patients who received Voraxaze^® within 3 days of admission to the hospital and those who received it after 3 days.

Results:

Among patients who received Voraxaze^® the average length of stay was 14.7 days, 4.0 of which were spent in the intensive care unit (ICU).  Patients in the non-glucarpidase group, with or without dialysis, spent an average of 21.9 days in hospital (p=0.025) and 8.3 days in the ICU (p=0.056).

Inpatient mortality among Voraxaze^® patients was 3.3% and 30-day and 90-day mortality 13.3% and 16.7%, respectively. Patients in the non-glucarpidase group, with or without dialysis, had a higher inpatient mortality rate of 20.8% (p=0.024). There was no statistically significant difference between groups in terms of 30-day and 90-day mortality.

Patients in the non-glucarpidase group treated with dialysis had an even longer length of stay in hospital (40 days) and in ICU (18) and a higher 90-day mortality (59%).

About Methotrexate Toxicity:

Methotrexate is a potent anticancer agent used in high doses (>500 mg/m²) to treat osteosarcoma, non-Hodgkin lymphoma, CNS lymphoma, and adult and paediatric acute lymphoblastic leukemia. Because methotrexate is primarily cleared by the kidneys, high doses can induce kidney dysfunction and 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. Early treatment with Voraxaze^® is associated with significantly lower rates of toxicity and mortality.^[i]

About Voraxaze:

Acute kidney injury due to high‐dose methotrexate (HDMTX) is a serious, life‐threatening toxicity that can occur in pediatric and adult patients. Voraxaze^® (glucarpidase) is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction. In clinical studies, patients treated with Voraxaze® experience rapid and sustained reductions in plasma MTX concentrations.^[ii],^[iii]

About BTG Pharmaceuticals.

BTG Pharmaceuticals provides antidotes that counteract the potentially life-threatening effects associated with exposure or overexposure to certain toxins. These acute care products are typically used in emergency rooms and intensive care units to treat patients for whom there are limited or no existing treatment options. We are dedicated to delivering quality medicines that make a real difference to patients through the development, manufacture, and commercialisation of pharmaceutical products. To learn more about BTG Pharmaceuticals, please visit: btgplc.com/pharmaceuticals.

For further information contact:

Chris Sampson, Corporate Communications Director

+44-(0)-20-7575-1595; Mobile: +44-(0)-7773-251-178

Indication and Limitations of Use

• Voraxaze® (glucarpidase) is indicated for the treatment of toxic plasma methotrexate concentrations (>1 μmol/L) in patients with delayed methotrexate clearance due to impaired renal function
• Voraxaze® is not indicated for use in patients who exhibit the expected clearance of methotrexate (plasma methotrexate concentrations within 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) or those with normal or mildly impaired renal function because of the potential risk of subtherapeutic exposure to methotrexate

Important Safety Information

Adverse Reactions

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

Warnings and Precautions

Serious Allergic Reactions

• Serious allergic reactions, including anaphylactic reactions, may occur

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 can overestimate the methotrexate concentration

Continuation and Timing of Leucovorin Rescue

• Leucovorin should not be administered within 2 hours before or after Voraxaze® dose because leucovorin is a substrate for Voraxaze®
• For the first 48 hours after Voraxaze®, administer the same leucovorin dose as given prior to Voraxaze®. Beyond 48 hours after Voraxaze®, administer leucovorin based on the measured methotrexate concentration
• Do not discontinue therapy with leucovorin based on the determination of a single methotrexate concentration below the leucovorin treatment threshold
• Therapy with leucovorin should be continued until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days
• Continue hydration and alkalinization of the urine as indicated

^[i] Voraxaze® [prescribing information]. BTG International Inc; 2013.

^[ii] 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; 28:3979-3986.

^[iii] 2013 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT), Clinical Toxicology 2013; 51(7):575-724. doi:10.3109/15563650.2013.817658.