Recurrent attacks of hereditary angioedema (HAE)

Active Ingredient: Donidalorsen

Indication for Donidalorsen

Population group: only adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Preventive action

Donidalorsen is indicated for routine prevention of recurrent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older.

For this indication, competent medicine agencies globally authorize below treatments:

80 mg once monthly

For:

Dosage regimens

Subcutaneous, 80 milligrams donidalorsen, once monthly.

Detailed description

The recommended starting dose in adult and adolescent patients aged 12 years and older is 80 mg donidalorsen by subcutaneous injection once monthly.

A dosing interval of 80 mg once every 2 months may be considered if the patient is well controlled (e.g., attack free) for at least 3 months while receiving donidalorsen.

Based on the clinical data, a gradual reduction in attack rate is seen as early as Week 1 after the initial dose of donidalorsen with an expected maximum effect after 1 month.

Consideration should be given to discontinuing treatment in patients with normal C1-INH HAE (nC1-INH) who have shown insufficient reduction in attacks after 4 months of treatment.

Donidalorsen is not intended for the treatment of acute HAE attacks.

Elderly

No dose adjustment is required for patients above 65 years of age.

Missed dose

If a dose is missed, the patient or caregiver should be instructed to administer the dose as soon as possible. Thereafter, dosing should be resumed at the prescribed dosing frequency (once monthly or once every 2 months) from the date of the most recently administered dose.

Changing from other HAE prophylactic medicinal products

The following treatment schedules (Table 1) are recommended for patients that are changing their HAE prophylactic therapy from berotralstat, a C1 esterase inhibitor, or lanadelumab to donidalorsen.

Table 1. Treatment schedule for patients changing from other prophylactic therapy to donidalorsen:

Other prophylactic therapyRecommended treatment schedule when changing to
donidalorsen
BerotralstatContinue taking the current dose of berotralstat for 14 days
after initiating treatment with donidalorsen.
C1 esterase inhibitorContinue taking the current dose of C1 esterase inhibitor for
14 days after initiating treatment with donidalorsen.
LanadelumabAdminister last dose of lanadelumab 14 days prior to initiating
treatment with donidalorsen.

Dosage considerations

Donidalorsen is to be administered as a subcutaneous injection in the abdomen, upper thigh region, or for caregivers only, the back of the upper arm. Rotation of the injection site is recommended.

Donidalorsen must not be injected into areas where the skin is tender, bruised, red, hard, infected or discoloured.

Active ingredient

Donidalorsen

Donidalorsen is a 2'-O-methoxyethyl–modified antisense oligonucleotide (ASO) conjugated to a triantennary N-acetylgalactosamine (GalNAc3) moiety that causes ribonuclease H1 (RNase H1) mediated degradation of prekallikrein (PKK) mRNA through selective binding to PKK mRNA, which results in reduced production of PKK protein. PKK is a pro-enzyme for plasma kallikrein, which results in the release of bradykinin, a potent vasodilator causing inflammation and swelling in hereditary angioedema (HAE).

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