PMID- 12196045
OWN - NLM
STAT- MEDLINE
DCOM- 20030225
LR  - 20181025
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 16
IP  - 4
DP  - 2002
TI  - Laronidase.
PG  - 316-8
AB  - BioMarin Pharmaceutical is developing laronidase, recombinant alpha-L-iduronidase 
      enzyme replacement therapy for the treatment of mucopolysaccharidosis I (MPS-I) 
      [the most severe form of this is called Hurler syndrome]. The company has 
      received US and European orphan drug designation for the enzyme and has 
      fast-track review status with the FDA. In 1998, BioMarin Pharmaceutical and 
      Genzyme General formed a joint venture for development and marketing of 
      laronidase. A Phase I trial in 10 patients with a range of disease severity of 
      MPS-I required for US and European filing was completed at the Harbor-UCLA 
      Medical Center in California. This open label trial involved weekly infusions 
      with laronidase. The two-year follow-up data revealed sustained and, in certain 
      parameters, improved clinical results recorded at the end of 1 year of therapy. 
      BioMarin and Genzyme General have completed a pivotal, Phase III trial in the 
      centres in the USA, Canada and Europe, including patients with Hurler-Scheie and 
      Scheie syndromes. In a multicentre, double-blind, placebo-controlled study, all 
      45 patients with MPS-I have received at least their initial weekly infusion of 
      laronidase. Patients are being evaluated over a 6-month period. BioMarin 
      Pharmaceutical and Genzyme General have filed on 15 April 2002 the first portion 
      of a 'rolling' BLA with the US FDA for use of laronidase in the treatment of 
      MPS-I. The companies are planning to complete the BLA filing in Q3 2002. The 
      application will include 6-month data from the ongoing open-label Phase III 
      extension study and also the 6-month data from the placebo-controlled part of the 
      Phase III study. In the open-label extension study, patients from both the 
      treatment and placebo arms of the Phase III trial received weekly infusions of 
      laronidase for at least 6 months. The response from the US FDA is anticipated 
      during the H1 of 2003. Both companies plan to initiate two new clinical trials in 
      patients with MPS-I. One study will enrol patients with MPS-I under 5 years old. 
      Another study will investigate laronidase in patients with advanced clinical 
      symptoms of MPS-I. Additionally, patients from the ongoing Phase III study will 
      continue to receive treatment with laronidase. On 1 March 2002, BioMarin and 
      Genzyme filed a marketing approval application with European regulatory 
      authorities for AldurazymeOE for the treatment of MPS-I. Mucopolysaccharidosis I 
      is a rare autosomal recessive lysosomal storage disorder caused by 
      alpha-L-iduronidase deficiency. Its manifestations in children can include growth 
      and developmental delay, enlargement of spleen and liver, skeletal deformity, 
      cardiac and pulmonary impairment, vision or hearing loss and mental dysfunction. 
      At present, bone marrow transplantation is the only available treatment.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
RN  - 0 (Recombinant Proteins)
RN  - EC 3.2.1.76 (Iduronidase)
SB  - IM
MH  - Animals
MH  - Clinical Trials, Phase I as Topic
MH  - Humans
MH  - Iduronidase/pharmacokinetics/*therapeutic use
MH  - Mucopolysaccharidosis I/*drug therapy/genetics
MH  - Recombinant Proteins/pharmacokinetics/therapeutic use
RF  - 4
EDAT- 2002/08/28 10:00
MHDA- 2003/02/26 04:00
CRDT- 2002/08/28 10:00
PHST- 2002/08/28 10:00 [pubmed]
PHST- 2003/02/26 04:00 [medline]
PHST- 2002/08/28 10:00 [entrez]
AID - 160409 [pii]
AID - 10.2165/00063030-200216040-00009 [doi]
PST - ppublish
SO  - BioDrugs. 2002;16(4):316-8. doi: 10.2165/00063030-200216040-00009.