Voraxaze™ - an enzyme that breaks down methotrexate (MTX)
Voraxaze fact sheet
Voraxaze Emergency Enquiries:
Europe/RoW:
David Briscoe Tel: +44 (0)207 246 9950 / Mob: +44 (0)7968 492 957
IDIS Customer Services:
UK & Republic of Ireland: +44 (0)1932 824100
Other EU countries:+44 (0)1932 824123
Out of hours emergency line: +44 (0)1932 824198
US:
US intravenous and US LV PK: AAIPharma: +1 866 918 1731
US intrathecal: Protherics Inc: +1 888 327 1027
Voraxaze US supplies
Availability
Please consult our Supply Details page for specific information on a country by country basis on how to obtain Voraxaze.
Product Information
Voraxaze (glucarpidase, previously known as carboxypeptidase G2 or CPG2) is a biological product designed to rapidly reduce the amount of blood levels of methotrexate (MTX), a commonly used cancer drug in the blood. High doses of MTX can cause kidney damage in some cancer patients and this can delay the elimination of MTX from the body. Prolonged exposure to high concentrations of MTX commonly results in serious toxic effects such as mucositis (painful mouth sores), reduced platelet and white blood counts (myelosuppression) , kidney failure and an increased risk of sepsis and in some instances death. A number of cancer patients die every year from MTX induced toxicity, typically due to sepsis. Voraxaze is the only drug which can remove MTX from the blood; dialysis is the only other way to remove MTX from the blood.
Voraxaze rapidly reduces the amount of MTX in the blood stream following a simple intravenous infusion. Voraxaze contains a recombinant enzyme (glucarpidase) which rapidly cleaves MTX into a non-toxic form. In one pivotal and two supportive studies, Voraxaze™ was able to achieve a clinically important reduction (CIR) in MTX concentration to ≤1 µmol/L in the majority of patients treated. This is a generally accepted threshold below which the risk of severe MTX toxicity is considered to be low. Consistently, Voraxaze reduced plasma or serum MTX concentrations by an average of >98% by the time of the first sample point, which was usually 15 minutes after the administration of Voraxaze in each of the three studies.
In clinical studies, a total 25/329 (8%) patients reported 50 adverse events with a possible relationship to Voraxaze™; about a third of these were considered to be allergic reactions (burning sensation, flushing, hot flush, allergic dermatitis, feeling hot, pruritis, hypersensitivity). Two of the adverse events were considered serious, hypertension and arrhythmia, but neither was definitively associated with use of Voraxaze™ and the latter was considered more likely to be associated with MTX.
Development status
Intervention
Voraxaze was granted orphan drug status in both the US and Europe in 2003. Marketing applications were previously submitted in the US and EU and subsequently withdrawn following requests for additional information. To support marketing applications in the US and EU, Protherics is undertaking a small clinical study, the leucovorin pharmacokinetic (LV PK) interaction study, to further characterise the drug-drug interaction between Voraxaze and leucovorin. This study is being conducted alongside the completion of a additional manufacturing and analytical work. Three consecutive conformance batches of Voraxaze, which are required for regulatory approval, are planned to be manufactured starting in the last half of 2008.
Protherics will start resubmitting a Biological License Application (BLA) to the US Food and Drug Administration (FDA) on a rolling basis in the second half of 2008. Protherics intends to seek a Priority Review, reducing the time for the BLA review from ten to six months from submission of the final part of the application and providing a potential approval in the US in 2010. Following feedback from the EMEA, we are investigating the availability of a suitable non-clinical model to generate data to support resubmission of a Marketing Authorisation Application in the EU.
Planned Use
A development programme has been initiated to expand the indications for Voraxaze to include planned repeated use, a market opportunity which could be worth up to US$100 million per annum.
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