The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has approved Dawnzera (donidalorsen, Otsuka Pharmaceutical Netherlands B.V.) for the prevention of swelling attacks in patients aged 12 years or older with hereditary angioedema. The approval was granted through the International Recognition Procedure. 

The subcutaneous injection, administered via a pre-filled pen either every 4 or 8 weeks, offers a new prophylactic approach for managing this potentially life-threatening inherited disorder, which is characterised by recurrent episodes of swelling and abdominal pain.

Targeting Kallikrein-Bradykinin Pathway

Hereditary angioedema is caused by deficiency or dysfunction of the C1 inhibitor protein, leading to excess bradykinin activity. This can trigger recurrent swelling episodes, including potentially life-threatening airway swelling. 

Donidalorsen reduces plasma kallikrein production, which lowers bradykinin levels in the blood, thereby helping to prevent symptoms linked to hereditary angioedema.

Reduction in Attack Frequency

The approval was based on the phase 3 OASIS-HAE trial involving patients aged 12 years or older with hereditary angioedema. In the study, 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients).

After 24 weeks, the mean number of attacks per month was approximately 0.4 in patients given donidalorsen every 4 weeks and about 1 attack in those given the medication every 8 weeks, compared with roughly 2.3 attacks in those given placebo. The mean attack rate from week 1 to week 25 was 81% lower in the 4-week group and 55% lower in the 8-week group than in the placebo group.

Donidalorsen also improved patients’ quality of life, based on a validated questionnaire measuring how symptoms affected daily activities.

Safety and Tolerability

The most frequent side effects, which may affect more than 1 in 10 people, were injection site reactions (including erythema, pain, itching, hardening, hematoma, bruising, skin scaling, allergic reaction, or swelling) and blood tests showing liver abnormalities.

In clinical trials, 98% of adverse events were mild or moderate in severity, with the most frequent being erythema at the injection site, headache, and nasopharyngitis.

More information can be found in the Summary of Product Characteristics and Patient Information Leaflets, which will be published on the MHRA Products website within 7 days of approval.