The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Elaprase (idursulfase) is a purified form of the lysosomal
enzyme human iduronate-2-sulfatase of recombinant DNA origin. It is
designed to replace the natural enzyme, increasing catabolism of
certain accumulated glycosaminoglycans (GAG), which abnormally
accumulate in multiple tissue types in patients with
mucopolysaccharidosis II (MPS-II, or Hunter syndrome).
Elaprase is specifically indicated for the treatment of Hunter
syndrome in adults and children ages 5 and older. The drug has been
shown to improve walking capacity in these subjects.
Elaprase is supplied as sterile, aqueous clear to
slightly-opalescent colorless solution for intravenous infusion.
Recommended initial dosing is 0.5 mg/kg administered via weekly
infusion. The initial recommended infusion rate is 8 ml/hr for the
first 15 minutes, which may be increased at 8/ml/hr increments at
15 minute intervals barring appearance of infusion reactions, to a
maximum of 100 ml/hr. Total infusion duration is generally 1-3
hours, and should not exceed 8 hours. Infusions may be slowed,
temporarily stopped, or discontinued for that dose if infusion
reactions occur (see Side Effects, below).
FDA approval of Elaprase was based on the results of one clinical
trial. This randomized, double-blind, placebo controlled trial
enrolled 96 subjects with Hunter's Syndrom, aged 5-31 years.
Subjects received Elaprase 0.5mg/kg every week, Elaprase 0.5mg/kg
every other week or placebo. The treatment duration was 53 weeks.
The primary efficacy endpoint was a score based on the change from
baseline to week 53 in distance walked during a 6 minute walk test
and the change in forced vital capacity percentages. The primary
endpoints showed the greatest statistical significant difference
between the weekly Elaprase treated group and the placebo group
(p=0.0049). The subjects in the Elaprase weekly group showed a 35
meter mean increase in distance walked versus the placebo group.
There was not a statistically significant difference in forced
vital capacity percentages between the groups.
Ongoing Study Commitments
- Shire commits to long-term safety and efficacy data in an
observational survey (the Hunter Outcome Survey, HOS) of patients
with Hunter Syndrome being treated with Elaprase. In addition to
clinical and laboratory tests that are part of standard medical
care for patients with Hunter's Syndrome, the survey will
collect data on patients from the six minute walk test, from a
subset of centers that will have the training a facilities to
collects the data in a standardized and reproducible manner, and
urinary GAG levels approximately every 6 to 12 months for at least
15 years. Assessments and data collected in the HOS will include
those listed in table 1 of the Hunter Outcome Survey summary
protocol version 1.0, dated October 31, 2005 and in the Safety
Specification and Pharmacovigilance Plan documented in the Elaprase
BLA. For pediatric patients in the HOS, data to be collected will
include standardized and replicated height, weight and head
circumference in conjunction with deformity assessments and
patients method of feeding. The survey will be designed to take
advantage of any opportunity to evaluate the effect of Elaprase on
female reproduction, pregnancy and lactation. The HOS data will be
analyzed at yearly intervals and the results will be submitted in
annual reports for BB-IND.
Protocol Submission: by November 2006
Study start: March 2007
Final report submission: September 2022
- Shire has agreed to conducting a study to evaluate the
pharmacokinetics, pharmacodynamis and safety in at least 18
children 5 years of age and under treated with Elaprase for at
least 6 months. In this population, pharmacodynamics will include
urinary GAG levels and changes in liver and spleen volumes. The
study will assess routine developmental milestones and growth. The
study will collect data on respiratory infections, surgical
interventions (e.g., PE tubes and adenoidectomy), hearing loss,
serious or severe infusion reactions, and other serious adverse
events. The study may be conducted as a separate study or as a
sub-study under a special protocol within the Hunter Outcome
Protocol Submission: November 2006
Study Start: March 2007
Final Report Submission: June 2009
- Shire has agreed to submit the final study complete study
TKT024EXT, titled "An Open Label Extension study of TKT024
Evaluating Long-term Safety and Clinical Outcomes of MPS II
Patients Receiving I2S Enzyme Replacement Therapy".
Study Completion: December 2007
Final Report Submission: August 2008
Adverse events associated with the use of Elaprase may include,
but are not limited to, the following:
- limb pain
- visual disturbance
In addition, Elaprase was shown to cause anaphylactiod reactions
in some patients during infusions. It is contraindicated in
patients with comprised respiratory function or acute respiratory
Mechanism of Action
Hunter's Syndrome is an X-linked recessive disease caused by
insufficient levels of the lysosomal enzyme iduronate-2-sulfatase.
This enzyme cleaves the terminal 2-O-sulfate moieties from the
glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate. Due
to the missing or defective iduronate-2-sulfatase enzyme in
patients with Hunter's Syndrome, GAG progressively accumulate
in the lysosomes of a variety of cells, leading to cellular
engorgement, organomegaly, tissue destruction and organ system
dysfunction. Treatment of Hunter's Syndrome patients with
Elaprase provides exogenous enzyme for uptake into cellular
lysosomes. Mannose-6-phosphate (M6P) residues on the
oligosaccharide chains allow specific binding of the enzymes to the
M6P receptors on the cell surface, leading to cellular
internalization of the enzyme, targeting to intracellular lysosomes
and subsequent catabolism of accumulated GAG.
Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P,
Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M,
Vijayaraghavan S, Wendt S, Puga A, Ulbrich B, Shinawi M, Cleary M,
Piper D, Conway AM, Kimura A A phase II/III clinical study
of enzyme replacement therapy with idursulfase in
mucopolysaccharidosis II (Hunter syndrome). Genetics in
medicine : official journal of the American College of Medical
Genetics 2006 Aug;8(8):465-73.