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).

Who developed
Hunterase?

#GC Biopharma #South Korea

GC Biopharma has developed Hunterase and obtained a marketing authorization in the Republic of Korea in 2012.
GC Biopharma is one of the top 5 pharmaceutical companies in Korea that has developed vaccines, plasma derivatives, Drugs for Rare Diseases, and other pharmaceutical products.

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 #urinary GAG #6MWT

Hunterase (Idursulfase-β) generated clinically significant reduction of urinary GAG and improvements in endurance as measured by 6MWT, and showed an acceptable safety profile for the treatment of MPS II.

A 24-week, randomized, single-blind, active comparator-controlled phase I/II trial was conducted in 31 patients with MPS II (6-35 years) to evaluate the efficacy and safety of Hunterase in the treatment of MPS II.

Primary Endpoint and Results

Study groups

Comparator group, 0.5 mg/kg/week (N=11)

Idursulfase-β group, 0.5 mg/kg/week (N=10)

Idursulfase-β group, 1.0 mg/kg/week (N=10)

Primary endpoint

The extent of reduction in urinary GAG excretion.

Results

Urine GAG excretion

Patients in all three groups exhibited reduction in urine GAG.

Urine GAG was significantly reduced in the 0.5 mg/kg (P=0.043) and 1.0 mg/kg (P=0.002) idursulfase-β groups compared with the active comparator group.

See the original chart

Comparator,
0.5 mg/kg/week (N)

Idursulfase beta,
0.5 mg/kg/week (N)

Idursulfase beta,
1.0 mg/kg/week (N)

Baseline

Comparator,
0.5 mg/kg/week (N)

129.1 (± 59.9)

Idursulfase beta,
0.5 mg/kg/week (N)

164 (± 53.19)

Idursulfase beta,
1.0 mg/kg/week (N)

124.7 (± 36.1)
4 weeks

Comparator,
0.5 mg/kg/week (N)

105.6 (± 56)

Idursulfase beta,
0.5 mg/kg/week (N)

112.3 (± 56.7)

Idursulfase beta,
1.0 mg/kg/week (N)

73.5 (± 35.7)
8 weeks

Comparator,
0.5 mg/kg/week (N)

109.8 (± 67.8)

Idursulfase beta,
0.5 mg/kg/week (N)

103.4 (± 56.4)

Idursulfase beta,
1.0 mg/kg/week (N)

67.1 (± 21.7)
12 weeks

Comparator,
0.5 mg/kg/week (N)

102.5 (± 55)

Idursulfase beta,
0.5 mg/kg/week (N)

110.9 (± 44.1)

Idursulfase beta,
1.0 mg/kg/week (N)

71.9 (± 24.4)
16 weeks

Comparator,
0.5 mg/kg/week (N)

111.1 (± 69.7)

Idursulfase beta,
0.5 mg/kg/week (N)

107 (± 46.2)

Idursulfase beta,
1.0 mg/kg/week (N)

63 (± 24.6)
20 weeks

Comparator,
0.5 mg/kg/week (N)

104.6 (± 62.6)

Idursulfase beta,
0.5 mg/kg/week (N)

111.6 (± 46.5)

Idursulfase beta,
1.0 mg/kg/week (N)

70.7 (± 24.5)
24 weeks

Comparator,
0.5 mg/kg/week (N)

105.3 (± 59.6)

Idursulfase beta,
0.5 mg/kg/week (N)

114.4 (± 45)

Idursulfase beta,
1.0 mg/kg/week (N)

74.5 (± 27.3)

All values are means ± SD.
*reference range : < 175 CPC unit/g Cr for ≤ 85 CPC unit/g Cr for > 9years.

Percent change in urinary GAG excretion

The reduced urine GAG level was maintained throughout the 24 weeks of treatment.

% Change, Urine GAG (Mean ± SEM)

*P = 0.043, **P = 0.002

Secondary Endpoints and Results

Secondary endpoints

6MWT: the distance walked in 6 minutes
Pulmonary function test (FVC): forced vital capacity
Cardiac evaluations (LVMI): left ventricular mass index
Cardiac evaluations (LVEF): left ventricular ejection fraction
Joint mobility (joint range of motion): flexion and extension of the shoulder, elbow, hip, and knee

Results

Percent change in 6MWT distance

Changes in 6MWT in patients with attenuated MPS II were significantly greater in the 0.5 mg/kg (P=0.003) and 1.0 mg/kg (P=0.015) idursulfase-β groups than in the active comparator group.

% Change, 6MWT

At 24 Weeks, the percent changes in 6MWT distance were significantly higher in idursulfase beta groups treated at dosages of 0.5 mg/kg/week (*P = 0.003) and 1.0 mg/kg/week (**P = 0.015), compared to comparator group. Grey bars represent the comparator group (N = 8), yellow bars represent the idursulfase beta 0.5 mg/kg/week group (N = 6), and orange bars represent the idursulfase beta 1.0 mg/kg/week group (N = 7).

Changes of secondary efficacy variables from baseline to 24 weeks

Idursulfase-β showed similar effectiveness to the active comparator in FVC, echocardiography, and joint range of motion.

Variables

Comparator,
0.5 mg/kg/week (N)

Idursulfase beta,
0.5 mg/kg/week (N)

Idursulfase beta,
1.0 mg/kg/week (N)

Variables

6MWT, m

Comparator,
0.5 mg/kg/week (N)

-9.1 ± 35.2 (8)

Idursulfase beta,
0.5 mg/kg/week (N)

61.6 ± 32.2 (6)

Idursulfase beta,
1.0 mg/kg/week (N)

38.4 ± 36.4 (7)
Variables

6MWT, % change

Comparator,
0.5 mg/kg/week (N)

-2.7 ± 9.2 (8)

Idursulfase beta,
0.5 mg/kg/week (N)

+23.5 ± 16.9 (6)

Idursulfase beta,
1.0 mg/kg/week (N)

+12.7 ± 11.9 (7)
Variables

FVC, L

Comparator,
0.5 mg/kg/week (N)

0 ± 0.1 (5)

Idursulfase beta,
0.5 mg/kg/week (N)

0 ± 0.1 (3)

Idursulfase beta,
1.0 mg/kg/week (N)

0.2 ± 0.1 (4)
Variables

FVC, % change

Comparator,
0.5 mg/kg/week (N)

+1.2 ± 8.4 (5)

Idursulfase beta,
0.5 mg/kg/week (N)

+7.9 ± 11.3 (3)

Idursulfase beta,
1.0 mg/kg/week (N)

+15.8 ± 7 (4)
Variables

LVMI, % change

Comparator,
0.5 mg/kg/week (N)

-1.7 ± 18 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

-5.1 ± 18.5 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

-5.9 ± 25.1 (10)
Variables

LVEF, % change

Comparator,
0.5 mg/kg/week (N)

+2.9 ± 11.9 (9)

Idursulfase beta,
0.5 mg/kg/week (N)

+2.5 ± 10.8 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

-1.4 ± 7.4 (10)

Joint range of motion, % changes

Comparator,
0.5 mg/kg/week (N)

Idursulfase beta,
0.5 mg/kg/week (N)

Idursulfase beta,
1.0 mg/kg/week (N)

Joint range of motion, % changes

Shoulder flexion

Comparator,
0.5 mg/kg/week (N)

23.4 ± 26.6 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

6.1 ± 10.7 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

6.7 ± 11.2 (10)
Joint range of motion, % changes

Shoulder extension

Comparator,
0.5 mg/kg/week (N)

1.8 ± 43 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

-20.4 ± 31.8 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

-1.2 ± 19.8 (10)
Joint range of motion, % changes

Elbow flexion

Comparator,
0.5 mg/kg/week (N)

7.2 ± 10.7 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

1.1 ± 9.4 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

-1.6 ± 11 (10)
Joint range of motion, % changes

Elbow extension

Comparator,
0.5 mg/kg/week (N)

25 ± 78.8 (9)

Idursulfase beta,
0.5 mg/kg/week (N)

3.8 ± 41.6 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

11.9 ± 94.5 (10)
Joint range of motion, % changes

Hip flexion

Comparator,
0.5 mg/kg/week (N)

4.5 ± 14 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

-4.1 ± 14.9 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

-1.3 ± 10.9 (10)
Joint range of motion, % changes

Hip extension

Comparator,
0.5 mg/kg/week (N)

22.6 ± 41.5 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

47.3 ± 98.9 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

4.2 ± 34.2 (8)
Joint range of motion, % changes

Knee flexion

Comparator,
0.5 mg/kg/week (N)

4.5 ± 7.9 (10)

Idursulfase beta,
0.5 mg/kg/week (N)

-0.7 ± 12.5 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

1.3 ± 8.2 (10)
Joint range of motion, % changes

Knee extension

Comparator,
0.5 mg/kg/week (N)

7.4 ± 40.1 (9)

Idursulfase beta,
0.5 mg/kg/week (N)

-28.1 ± 59.1 (10)

Idursulfase beta,
1.0 mg/kg/week (N)

0 ± 43.6 (8)

*6WMT, 6-minute walk test; FVC, forced vital capacity; LVMI, left ventricular mass index; LVEF, left ventricular ejection fraction

Safety Information

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

Precautions

Warning

Patients with compromised respiratory function or acute respiratory disease may be at higher risk of life-threatening complications from infusion reactions.

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 Package Insert

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

Orphanet J Rare Dis. 2013;8:42
Mol Ther Methods Clin Dev. 2021;21:67-75
Mol Genet Metab. 2015;114(2):156-60

Hunterase

About Hunterase

What is Hunterase?

Composition

Indication

Who developed Hunterase?

How does Hunterase work in Our Body?

Clinical Trials

Primary Endpoint and Results

Study groups

Primary endpoint

Results

Urine GAG excretion

Patients in all three groups exhibited reduction in urine GAG.

Percent change in urinary GAG excretion

The reduced urine GAG level was maintained throughout the 24 weeks of treatment.

Secondary Endpoints and Results

Secondary endpoints

Results

Percent change in 6MWT distance

Changes in 6MWT in patients with attenuated MPS II were significantly greater in the 0.5 mg/kg (P=0.003) and 1.0 mg/kg (P=0.015) idursulfase-β groups than in the active comparator group.

Changes of secondary efficacy variables from baseline to 24 weeks

Idursulfase-β showed similar effectiveness to the active comparator in FVC, echocardiography, and joint range of motion.

Safety Information

Precautions

Storage And Shelf-life

Adverse Reactions

ENG Package Insert

How to Use

Recommended dosage

Automatic calculation

Enter your weight and it will be calculated automatically.

Injection Process

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

Recommendation

Precautions in Storage and Handling

In an unaffected individual

Diagram of the IDS sequence

In an MPS II patient (Hunter syndrome)

ERT with Hunterase (Idursulfase-β)

What is
Hunterase?

Who developed
Hunterase?

How does
Hunterase work in
Our Body?

Storage And
Shelf-life

Adverse
Reactions