In patients with hereditary angioedema (HAE), the C1-inhibitor blood protein does not function properly, allowing bradykinin peptides to build up in the body. These then cause inflammation and fluid leakage; as the fluid leaks into body tissues, it causes swelling. HAE is characterized by these attacks of severe, sudden, and unexplained swelling under the skin. In some cases, these attacks can be difficult to treat. But a new study highlights the potential of treating or reducing HAE attacks using donidalorsen.
What is Hereditary Angioedema (HAE)?
Hereditary angioedema (HAE) results from a genetic defect on chromosome 11 which causes the C1-inhibitor deficiency. The condition is aptly named: hereditary (inherited), angio (related to blood vessels), edema (swelling caused by excess fluid). HAE attacks may be caused by a trigger – such as injuries, stress, infection, or hormonal fluctuations – they also often occur without a trigger. While HAE affects both males and females, females may be more affected due to more frequent hormonal changes. Symptoms and characteristics include:
- Swelling of the extremities to 2x+ their normal size
- Swollen face and eyelids to the point of unrecognizability
- Gastrointestinal inflammation
- Abdominal pain
- Nausea and vomiting
- Abdominal distention
- Throat (larynx, esophagus, trachea) swelling
- Difficulty breathing
- Fatigue
- Muscle pain
Evaluating Donidalorsen
According to Medical Dialogues, the study, published in the New England Journal of Medicine, explored the efficacy of donidalorsen for reducing the risk and prevalence of HAE in adult patients. Ionis Pharma describes donidalorsen as:
A ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of prekallikrein, or PKK [which] plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE.
This is designed to overcome the limitations and tolerability issues associated with the current standard-of-care: prophylactic treatments.
Altogether, 20 patients enrolled in this Phase 2 clinical trial. Patients received either 80mg donidalorsen, administered subcutaneously, or a placebo. Ultimately, the findings showed that:
- There was a much higher risk of HAE attacks in the placebo group (mean monthly rate: 2.21) compared to those taking donidalorsen (mean monthly rate: 0.23).
- Patients taking donidalorsen reported a significant improvement in quality-of-life (QOL).
- While side effects did occur in both groups, there was a higher rate of adverse reactions within the group receiving the placebo.
