New molecular entity
Development and Regulatory status
Jan 22Approved in EU .
Nov 21Recommended for EU approval under exceptional circumstances by CHMP “to reduce toxic plasma methotrexate concentration in adults and children (aged 28 days and older) with delayed methotrexate elimination or at risk of methotrexate toxicity”. Voraxaze will be available as 1000 IU/ml powder for solution for injection .
Aug 20Filed in EU via centralised procedure .
May 12Launched in the US .
Jan 12Approved in US to reduce toxic methotrexate levels due to kidney failure .
Sep 11Filed in US and given priority review status .
Apr 11Glucarpidase was granted orphan drug status in both the US and Europe in 2003. Company filing in the US on a rolling basis; complete submission expected mid-2011. They will seek a Priority Review. Following feedback from the EMA the company are investigating a suitable non-clinical model to generate data to support resubmission in the EU .
Nov 08Filed in US with Fast track designation. Launch anticipated Q4 09 (10)
May 07MAA withdrawn May 07 (9)
May 07EU submission for chemoprotection withdrawn
May 07FDA has requested additional manufacturing and stability data as well as a 12-patient study to assess the drug's interaction with leucovorin. FDA have agreed that it can be re-filed as a rolling submission early next year and could therefore be on the US market in 2009. The company are hoping that the extra info provided to FDA will satisfy requests from EU agency - resulting in resubmission of EU approval
Jan 07EMEA have requested more manufacturing data which has pushed back anticipated approval to 2H08. Fast track in US. Product is already being used on a compassionate basis in US and on a named-patient basis in EU and rest of world.
Nov 06Marketing application withdrawn in US.
Sep 06EU approval expected in the first half of 2007
Sep 06Filed in US Sep 06
Jan 03Positive Opinion granted by EC Orphan Medicinal Products Committee; plan to file for approval in EU and US by end of 2003. Company expect launch in US in 2005
Approximately 5 to 10 patients a year (adults/paediatrics) develop a significant deterioration in renal function after the start of high dose methotrexate, have toxic plasma methotrexate levels and are at risk of life-threatening methotrexate-induced toxicities .
Trial or other data
Mar 21SERB complete acquisition of BTG Specialty Pharmaceuticals .
Jun 12Data supporting approval in the US reported at ASCO. 492 patients (median age 18 years (range: 5 weeks to 85 years) experiencing renal toxicity and delayed elimination of methotrexate (MTX) were treated with Voraxaze® (50 U/kg IV) in compassionate use trials conducted in the US and EU from November 1993 to June 2009. 41% of patients had NHL, 30% had osteogenic sarcoma, 23% ALL, and 7% other malignancies. The median pre-Voraxaze® MTX concentration was 17 micromoles/litre. 76% received a single dose Voraxaze®, 22% received 2 doses, and 2% received 3 doses. The first dose of Voraxaze® was given at a median of 3 days after MTX administration. 156 patients had MTX concentrations determined by HPLC. At first measurement (median 15 minutes post-Voraxaze®) serum MTX was reduced by a median of 99% relative to baseline. At the last measurement (median 40 hours post-Voraxaze®) median serum MTX reduction remained at 99% compared with baseline. Among 410 patients with pre-Voraxaze® renal impairment (measured as common terminology criteria for adverse events Grade 2 or higher), 64% recovered to Grade 0 or 1 after a median of 12.5 days post-Voraxaze®. AEs included paresthesia (2.0%), flushing (1.8%) and headache (1.0%). 8% of patients died within 30 days of Voraxaze® administration of causes unrelated to Voraxaze®, as judged by the treating physician .
Nov 06Marketing application withdrawn in US following FDA's request for manufacturing information (4). BLA withdrawal in US will cause a delay of approx one year, although it is already available there on a compassionate-use basis. US approval now expected in the second half of 2008 (5).