Date: 2012-01-28
Type of information:
Product name: Voraxaze®
Compound: glucarpidase injection
Therapeutic area:
Action mechanism: Voraxaze® works by breaking down methotrexate into its inactive metabolites which are then eliminated from the body by routes other than the kidney (primarily the liver).
Company: BTG International (UK)
Disease: treatment of toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function.
Latest news: * On January 17, 2012, the FDA approved glucarpidase injection (Voraxaze, BTG International Inc.) for the treatment of toxic plasma methotrexate concentrations (> 1 micromol/L) in patients with delayed methotrexate clearance due to impaired renal function. Safety data were evaluated in 290 patients treated in two single-arm, open-label, multicenter trials. These trials enrolled patients who had markedly delayed methotrexate clearance secondary to renal dysfunction. The median age was 17 years (1 month to 85 years), 64% were male, 32% had osteogenic sarcoma or sarcoma and 63% had leukemia or lymphoma. The most common adverse reactions (incidence >1%) were paraesthesias, flushing, nausea and/or vomiting, hypotension and headache.
The approval was based on the pharmacodynamic endpoint of a rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, defined as an attainment of plasma methotrexate concentration ?1 micromol/L within 15 minutes following glucarpidase administration and sustained for up to 8 days.
Efficacy was established in 22 patients with delayed methotrexate clearance (more than 2 standard deviations above the average indicated on standard nomograms) secondary to renal dysfunction. The efficacy assessment was limited to patients having pre- and post-treatment plasma samples collected and handled according to a validated procedure to yield reliable methotrexate measurements by HPLC.
All patients received glucarpidase, 50 Units/kg, as an intravenous injection over 5 minutes. Patients with pre-glucarpidase methotrexate concentrations >100 ?mol/ L were to receive a second dose of glucarpidase 48 hours after the initial dose. All patients received vigorous intravenous hydration, urinary alkalinization, and leucovorin rescue. Ten of the 22 patients met the criteria for RCSIR [45% (95% CI: 27, 65)]. Efficacy was dependent on pre-treatment methotrexate levels. Ten of 13 patients (77%) who had baseline methotrexate levels between 1-50 micromol/L achieved an RSCIR, however, none of the 9 patients with pre-glucarpidase methotrexate concentrations > 50 micromol/L attained this endpoint. All evaluable patients exhibited more than 95% reduction in methotrexate concentration from pre-treatment baseline levels that was maintained for up to 8 days following glucarpidase therapy.
* On April 30, 2012, BTG International has announced the launch of Voraxaze® (glucarpidase) in the US. Voraxaze® is indicated for the treatment of toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function. BTG also announces that the company is partnering with ASD Healthcare, part of the AmerisourceBergen Corporation, to be the sole distributor for Voraxaze® in the US.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2012-01-17
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2003-08-19
Orphan status UE: 2003-02-03
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
