(Vienna, 27-03-2023) In the case of the rare genetic disease of hereditary angioedema (HAE), swelling occurs in one or more parts of the body without a recognisable trigger. An HAE attack can be life-threatening especially if the upper respiratory tract is affected. Active substances for on-demand medication are currently only available in the form of injections and transfusions. In a phase 2 study led by the University Hospital Frankfurt and the Charité - Universitätsmedizin Berlin and with the cooperation of the Medical University of Vienna, the efficacy of an orally administered substance for acute attacks has now been proven for the first time. The study results were published in the renowned journal "The Lancet".
Patients with HAE have a mutation in their genetic make-up. The genetic disease manifests itself mainly during childhood and adolescence and remains symptomatic in most affected individuals throughout their lives. It manifests as severe, localised swellings of the skin and mucous membranes that can occur in various parts of the body. Abdominal attacks are particularly painful, lasting several days and confining sufferers to bed if left untreated. If the upper airways are affected, an HAE attack can be life-threatening. Laryngeal oedema is one of the most common causes of death in HAE patients. Therefore, treatment guidelines recommend the treatment of the attacks as early as possible. Studies have shown that prompt treatment significantly reduces the time to symptom relief and the overall duration of the attack.
Oral therapies instead of transfusions or injections
The currently approved therapies for HAE consist of on-demand medications and prophylactic action, i.e. substances for acute treatment or the prevention of attacks. However, the administration of these drugs has been difficult so far: Patients receive the substance through infusions or injections. These methods require training, lead to delays in treatment and can cause undesirable side effects such as pain and hypersensitivity reactions at the transfusion or site of the injection. With the orally administered drug now being researched, these serious side effects could be avoided. Compared to placebo, Sebetralstat provided faster symptom relief, reduced the severity of the seizures and extended the time to conventional treatment significantly. Sebetralstat is rapidly absorbed by the body and reaches maximum plasma concentrations within one hour, which is crucial for symptom relief.
The study recently published in "The Lancet" demonstrated that an effective oral therapy for acute angioedema attacks in HAE is possible. In addition to the University Hospital Frankfurt and the Charité - Universitätsmedizin Berlin, scientists from several European countries, the USA, New Zealand and Canada were involved in the study. At MedUni Vienna, Tamar Kinaciyan (Department of Dermatology), an internationally renowned researcher in the field of hereditary angioedema, played a key role in proving Sebetralstat to be an effective treatment for acute attacks.
Based on the promising results of the study, a phase 3 clinical trial with Sebetralstat is currently being conducted to re-evaluate the need-based treatment with the active substance.
Publication: The Lancet
Investigational oral plasma kallikrein inhibitor Sebetralstat for on-demand treatment of hereditary angioedema;
Aygören-Pürsün, E.; Zanichelli, A.; Cohn, D. M., Cancian, M., Hakl, R., Kinaciyan, T., Magerl, M., Martinez-Saguer, I., Stobiecki, M., Farkas, H., Kiani-Alikhan, S., Grivcheva-Panovska, V., Bernstein, J. A., Li, H. H., Longhurst, H. J., Audhya, P. K., Smith, M. D., Yea, C. M., Maetzel, A., Lee, D. K., Feener, E. P., Gower, R., Lumry, W. R., Banerji, A., Riedl, M. A., Maurer, M.;
The Lancet; 11.02.2023 (Epub ahead of print).
DOI: doi.org/10.1016/S0140-6736(22)02406-0