BTG plc, the specialist healthcare company, today announces that it has received regulatory approval from the US Food and Drug Administration (FDA) for its Biologics License Application (BLA) for Voraxaze® (glucarpidase). The approval of Voraxaze® was granted under priority review, a designation that is given to therapies that offer major advances in treatment or provide a treatment where there is no adequate alternative therapy.
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. It 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). Voraxaze® is the first and only drug able to reduce toxic plasma methotrexate levels.
High dose methotrexate chemotherapy is used to treat or prevent the recurrence of certain types of cancer, such as osteosarcoma, leukemia, and lymphoma. Some patients treated with methotrexate develop impaired kidney function, which leads to the accumulation of toxic levels of methotrexate in the blood and puts patients at risk of additional toxicity.
The most common related adverse events in clinical trials were paresthesia (a sensation of tingling or burning on the skin), flushing, nausea, vomiting, hypotension and headache.
Louise Makin, Chief Executive Officer of BTG, commented: “Voraxaze® is the first product BTG has taken through to approval in the US and we look forward to its launch over coming months. It will be sold by our existing specialty pharmaceuticals sales force, with the addition of a few extra personnel, alongside our established emergency room medicines, CroFab® and DigiFab®.”
Guenter R. Janhofer, Chief Medical Officer and Head of Development at BTG, added: “Today’s FDA approval of Voraxaze® has the potential to help patients in the rare event that they experience delayed methotrexate elimination due to impaired renal function. In the clinical trials which led to approval, patients achieved rapid and sustained reductions in plasma methotrexate concentrations.”
The FDA approval is based upon data from 290 patients who were treated in 2 single-arm, open-label, multicentre trials.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 FDA 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 μmol/L within 15 minutes following glucarpidase administration and sustained for up to 8 days.
The efficacy of Voraxaze® was established in a subset consisting of 22 treatment-evaluable patients in one of the two clinical studies. Patients enrolled in this study exhibited 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 chromatographic methodology.
Ten of the 22 patients achieved RSCIR [45% (95% CI 27, 65%)]. 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.
Voraxaze® is to be administered as a single intravenous injection of 50 Units per kg.
The most common adverse reactions (incidence >1%) were paresthesias, flushing, nausea and/or vomiting, hypotension and headache.
Healthcare providers should note that:
• Methotrexate concentrations within 48 hours following glucarpidase administration can only be reliably measured by a chromatographic method due to interference from metabolites [4-deoxy-4-amino-N10-methylpteroic acid (DAMPA)]. Measurement of methotrexate concentrations within 48 hours of glucarpidase administration using immunoassays can overestimate the methotrexate concentration.
• Leucovorin should not be administered within 2 hours before or after a glucarpidase dose because leucovorin is a substrate for glucarpidase.
Forward Looking Statements
This communication may contain forward-looking statements with respect to the financial condition, results of operations, businesses and prospects of BTG plc (“BTG”). These statements are based on current expectations and involve risk and uncertainty because they relate to events and depend upon circumstances that may or may not occur in the future. There are a number of factors which could cause actual results or developments to differ materially from those expressed or implied by these forward-looking statements. Any of the assumptions underlying these forward-looking statements could prove inaccurate or incorrect and therefore any results contemplated in the forward-looking statements may not actually be achieved. Nothing contained in this press release or communicated verbally should be construed as a profit forecast or profit estimate. Investors or other recipients are cautioned not to place undue reliance on any forward-looking statements contained herein. BTG undertakes no obligation to update or revise (publicly or otherwise) any forward-looking statement, whether as a result of new information, future events or other circumstances. Neither this communication nor any verbal communication shall constitute an invitation or inducement to any person to subscribe for or otherwise acquire securities in BTG.
For further information contact:
Andy Burrows, Director of Investor Relations
T: +44 (0)20 7575 1741 / M: +44 (0)7990 530605
Rolf Soderstrom, Chief Financial Officer
T: +44 (0)20 7575 0000
Ben Atwell - T: +44 (0)20 7831 3113