Zirdawny (donidalorsen)
Zirdawny is approved for routine prevention of recurrent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older. Zirdawny contains the active ingredient donidalorsen (as sodium).
Hereditary angioedema (HAE) is a rare inherited condition. It usually occurs when the body does not have enough of a protein called C1 inhibitor, or C1 inhibitor does not work properly. C1 inhibitor normally helps control inflammation and swelling by regulating the immune system.
People with HAE have episodes of swelling, known as angioedema attacks, in different parts of the body. These attacks can be painful and potentially life-threatening. Swelling may affect:
- hands and feet
- face, eyelids, lips or tongue
- voice-box (larynx), which may make breathing difficult
- genitals
- stomach and intestines.
Angioedema attacks can happen without warning and may be triggered by things like stress, injury, infection, or certain medications.
Zirdawny contains the active ingredient donidalorsen. It belongs to a group of medicines called antisense oligonucleotide.
In people with HAE, a protein called C1 inhibitor does not work properly or is present at low levels. As a result, plasma kallikrein becomes activated leading to high levels of plasma kallikrein and overproduction of bradykinin. Too much bradykinin causes fluid to leak from blood vessels into surrounding tissues, leading to the recurrent swelling, known as angioedema attacks, seen in HAE.
Donidalorsen helps prevent angioedema attacks by lowering the production of prekallikrein and consequently lowering levels of plasma kallikrein. This in turn reduces the levels of bradykinin in the blood and lowers the risk of ongoing HAE symptoms (i.e. swellings).
Zirdawny is given as a subcutaneous (below the skin) injection every month. Injections every 2 months may be considered, if the attacks are well controlled while taking Zirdawny.
The effectiveness of Zirdawny was assessed in one main clinical trial (Study CS05 – OASIS-HAE) and one supporting trial. The safety of Zirdawny was assessed combining data from two clinical trials, Study CS05 and Study CS02.
The main clinical trial, Study CS05, was conducted over 24 weeks and recorded the number of investigator-confirmed angioedema attacks experienced by 90 participants with HAE, aged 12 years and older. The study compared:
- 45 participants in the treatment group given Zirdawny at 4-weekly intervals,
- 23 participants in the treatment group given Zirdawny at 8-weekly intervals,
- 22 participants given the placebo (a medicine containing no active ingredients) at 4-weekly intervals/8-weekly intervals.
The supporting trial assessed the effectiveness of Zirdawny in participants with HAE with normal C1-inhibitor (nC1-INH-HAE).
Key findings from clinical studies
- In Study CS05, Zirdawny given every 4 weeks or 8 weeks reduced the rate of angioedema attacks compared to placebo, and this difference was statistically meaningful.
- At 24 weeks, 91% of participants receiving Zirdawny every 4 weeks, and 74% of participants receiving Zirdawny every 8 weeks had well-controlled disease, based on the Angioedema Control Test (AECT), compared to 41% of participants receiving the placebo.
- At 24 weeks, meaningful improvement in health-related Quality of Life was reported for Zirdawny treatment groups compared to placebo, using the validated questionnaire ‘Angioedema Quality of Life Questionnaire (AE-QoL)’.
- The rate of treatment related adverse reactions (side effects or unexpected outcomes) was similar for donidalorsen (70.6%) and placebo (81.8%).
- The most common side effect in participants treated with Zirdawny were injection site reactions (24.4%). No deaths or serious adverse drug reactions occurred during clinical trials.
The TGA decided that the application provided sufficient evidence supporting the safety and effectiveness of Zirdawny and the medicine can be registered in Australia.
More detailed information on why the TGA approved Zirdawny will be published in the upcoming Australian Public Assessment Report (AusPAR).
For comprehensive information on potential side effects and risks, refer to the Consumer Medicine Information (CMI) leaflet or Product Information (PI) document.
This decision summary will not be updated to reflect any subsequent changes and may therefore not contain the most current information about the medicine. For the latest information, refer to the medicine’s CMI or PI.
The CMI leaflet offers guidance for consumers to support safe and effective use of the medicine. The CMI includes information on dose, how to use the medicine properly, potential side effects, safety precautions, storage instructions and more.
The Australian CMI for Zirdawny can be accessed through the searchable TGA eBusiness Services or ARTG databases.
The PI document provides essential prescribing information for health professionals, including details on dosage recommendations, pregnancy category, contraindications, precautions and potential side effects.
The Australian PI for Zirdawny can be accessed through the searchable TGA eBusiness Services or ARTG databases.
For health advice and information, including a symptom checker and service finder refer to the healthdirect website.
For advice on prescription medicines, over the counter medicines and other medicines (including complementary medicines) call Medicines Line.
For information on medicines subsidised by the Australian Government refer to the Pharmaceutical Benefits Scheme (PBS) website.
For data and reports on health and welfare topics in Australia refer to the Australian Institute of Health and Welfare website.
After proper training on correct injection technique, a patient or caregiver may inject Zirdawny if their doctor determines it is appropriate. Comprehensive instructions for administration using the pre-filled pen are provided in the package insert.
Your doctor may wish to check your blood count and liver function with a blood test, before and during your treatment with Zirdawny.