Hunterase

About Hunterase Clinical Trials Safety Information How to Use

About Hunterase

What is
Hunterase?

#Idursulfase-β #Idursulfase beta #orphan drug #MPS II #rare disease #ERT #Hunter syndrome

Composition

Active ingredient : Idursulfase-β 6.0 mg (3 ml in 1 vial)

Indication

Hunterase (Idursulfase-β) is indicated for patients with Hunter Syndrome (Mucopolysaccharidosis II, MPS II) as an enzyme replacement therapy (ERT).

How does
Hunterase work in
Our Body?

In an unaffected individual
In an MPS II patient
(Hunter syndrome)
ERT with Hunterase (Idursulfase-β)

Clinical Trials

#Idursulfase-β #Idursulfase beta #Phase I/II #urinary GAG #6MWT #FVC #LVMI #LVEF

Hunterase (Idursulfase beta) is a safe and effective treatment option in mucopolysaccharidosis II (MPS II), addressing crucial somatic ailments presented by patients.

In Phase III, participants in the idursulfase beta groups (n = 24) were male Asians (mean age, 12.0 years). Idursulfase beta was superior to placebo in 6-minute walk test improvement (62.2 vs 7.3 m, P < .0001). Decrease in urine glycosaminoglycan excretion (-71.13% vs 21.39%, P < .0001) and reduction in the liver (-26.67% vs -0.80%, P < .0001) and spleen volumes (-26.46% vs 7.2%, P < .0001) were significant.
The safety profile of idursulfase beta was satisfactory.

This study demonstrated the superiority of idursulfase beta over placebo in improving 6-MWT results. Furthermore, idursulfase beta significantly reduced urine GAG excretion and liver and spleen volumes while exhibiting a safety profile comparable to that of idursulfase.

Study design

*Historical placebo cohort from a previous idursulfase trial (TKT024)2 R,
randomization; Tx, treatment; f/u, follow-up; MPS II, mucopolysaccharidosis type II.

Methods

The study comprised two sequential parts.

In Part 1,

a randomized, double-blind study,
idursulfase or idursulfase beta were given for 52 weeks.

In the open, single cohort Part 2 study,

additional participants received idursulfase beta for 52 weeks.
Data from the idursulfase beta groups from Parts 1 & 2 were pooled for comparisons with the historical placebo group (n=32)

Primary endpoint

A change in the 6-minute walk test
(6-MWT) at week 53

Secondary endpoints

Changes in:

6MWT at other time points
Urine total GAG levels
Heparan sulfate (HS) and Dermatan sulfate (DS) levels
Liver volume
Spleen volume
Absolute forced vital capacity (FVC)
Echocardiographic parameters assessing cardiac size and function

Primary Endpoint and Results

The mean change at week 53 in the idursulfase beta group demonstrated the superiority compared to the histrorical placebo group.
Idursulfase group was significantly greater than that in the historical placebo group (62.2 vs 7.3 m, P < .0001), with a lower bound of the 1-sided 95% CI of 48.05 m.
Per-protocol analysis showed a similar level of significant change in the idursulfase beta group (mean = 62.1 m, median = 52.8 m).

Changes in 6-minute walk test (6MWT) throughout the study period

*Historical placebo from a previous idursulfase trial (TKT024)²

Secondary Endpoints and Results

Mean percent change in urine total GAG concentration at week 53 showed a significant reduction in the idursulfase beta group compared with that in the historical placebo group (-71.13% vs 21.39%, P < .0001)

% changes in urine total GAG, HS, and DS level at week 53

The error bar represents a 90% CI.
*Historical placebo from a previous idursulfase trial (TKT024)²
GAG, glycosaminoglycan

% changes in Liver and Spleen Volume at week 53

Immunogenicity

Idursulfase beta showed a lower rate of persistent NAb+ (16.7% vs 62.5%) compared with idursulfase, and in the beta group, NAb− patients had slightly greater HS/DS reductions, while NAb+ patients experienced more SAEs and acute AEs.

Persistent NAb+ Proportion by Treatment Group

Proportion of patients with neutralizing antibody positivity (NAb+) in the idursulfase beta group (A) or idursulfase group (B). a Only when an antidrug antibody (ADA) test was positive, an NAb test was carried out subsequently.

Idursulfase beta (n=24)

Idursulfase (n=8)

Safety

In the idursulfase beta group, most adverse events were mild to moderate with no treatment discontinuations, and the proportion of patients with persistent neutralizing antibodies during the treatment period was 16.7%, notably lower than 62.5% observed with the active comparator.

	Idursulfase beta (Parts 1&2) (n=24)	Idursulfase (Part 1) (n=8)
Anti-drug antibodies, n(%)
Positive at least once	23 (95.8)	8 (100.0)
Positive ≥ three times consecutively	21 (87.5)	8 (100.0)
Neutralizing antibodies [Neutralizing assay], n(%)
Positive at least once	9 (37.5)	8 (100.0)
Positive ≥ three times consecutively	4 (16.7)	5 (62.5)

Safety Information

Hunterase should be administered by a healthcare professional according to the prescribing information.

PRECAUTIONS

WARNING

Life-threatening anaphylactic reactions have been observed in some patients during infusions of a medicine similar to Hunterase. Reactions have included respiratory distress, hypoxia, hypotension, seizure, and/or angioedema. Because of potential of severe infusion reactions, appropriate medical support should be readily available when Hunterase is administered. When severe infusion reactions occurs, subsequent infusions should be managed by using antihistamines and/or corticosteroids prior to or during infusions, a slower rate of Hunterase administration, and/or early discontinuation of the Hunterase infusion if serious symptoms occur.

Inject with care

Patients with serious recurrent reactions related to injection after infusion of Hunterase.
Patients with history of anaphylaxis to ingredients of Hunterase.
Patients with history of shock to ingredients of Hunterase.

General precautions

Life-threatening anaphylactic reactions have been observed in some patients during infusions of a medicine similar to Hunterase. Reactions have included respiratory distress, hypoxia, hypotension, seizure, and/or angioedema. Because of potential of severe infusion reactions, appropriate medical support should be readily available when Hunterase is administered. When severe infusion reactions occur, subsequent infusions should be managed by using antihistamines and/or corticosteroids prior to or during infusions, a slower rate of Hunterase administration, and/or early discontinuation of the Hunterase infusion if serious symptoms occur.
Interaction with other medicinal products : No formal drug-drug interaction studies have been conducted with Hunterase.

Carcinogenesis, Mutagenesis, Impairment of fertility

Long-term studies to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with Hunterase.

Pregnancy

Reproduction studies in pregnant female animals have not been conducted with Hunterase. It is also not known whether Hunterase can cause fatal harm when administered to a pregnant woman or can affect reproduction capacity.
Nursing mothers

It is not known whether this product is excreted in human milk.
Pediatric use

Patients in the clinical studies were older than age 38 months and younger than age 35 years. Children, adolescents, and adults responded similarly to treatment with Hunterase.

Storage And
Shelf-life

Store at a 2 ºC to a 8 ºC in a hermetic container.
The shelf-life of this product is 36 months from the date of manufacture.

ADVERSE
REACTIONS

All adverse reactions in patients treated with Hunterase weekly for 24 weeks compared with the active comparator during the clinical trial are shown in the pdf file below. 3 serious adverse reactions were observed: 2 cases of otitis media and 1 case of gastroenteritis. However, all cases were determined as ‘not-related’ to Hunterase.
Adverse reactions associated with Hunterase were urticaria, rashes, and pruritus.
All adverse reactions were mild and controlled by adjusting the infusion rate and using proper drug treatments.

ENG Official Insert Paper

PDF Download

How to Use

Recommended Dosage

Method: intravenous infusion, once weekly.
Each vial of Hunterase contains 2 mg/ml of Idursulfase-β.
One vial contains 6 mg of Idursulfase-β in 3 ml solution and is for single use only.
Recommended dosage of Idursulfase-β protein = Patient’s weight (kg) * 0.5 mg/kg

Automatic Calculation

Enter your weight and it will be calculated automatically.

1 ml

Hunterase 1 Vial
Idursulfase-ß 6.0 mg / 3 mL

Please enter your weight (kg)

kg

Recommended dosage of Idursulfase-β = Patient’s weight (kg) * 0.5 mg/kg

Idursulfase-β (mg)

mg

Hunterase (vial)

vials

Injection Process

This information is based on the common clinical practice. It is not published or written in the package insert.

01

Open the Hunterase Vial(s) after determining the required number of vials using the above calculator.

02

Sterile the Hunterase Vial Cap.

03

Dilute Hunterase in 100 ml of normal saline (0.9% sodium chloride injection) in the infusion bag.

04

Adjust the infusion rate considering the patient’s condition.

Recommendation

The initial infusion rate for the first 15 minutes – 8 mL/hr. If the infusion is well tolerated, the rate may be increased by 8 mL/hr increments every 15 minutes. The infusion rate should not exceed 100 mL/hr.

Precautions in Storage and Handling

Store Hunterase vials under refrigeration at 2 ºC to 8 ºC
Protect from light without freezing and do not shake it.
Do not use Hunterase after the expiration date on the vial.
This product contains no preservatives. The diluted solution should be used immediately. If immediate use is not possible, the diluted solution can be stored refrigerated at 2 ºC to 8 ºC for up to 48 hours, or must be administered within 8 hours if held at room temperature.

References