Garadacimab is approved for the routine prevention of recurrent attacks of hereditary angioedema (HAE). In an early benefit assessment, the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this monoclonal antibody offers an added benefit compared with the appropriate comparator therapy (ACT) for adults and adolescents aged 12 and older.
The (German-language) report was published in June 2025, an English translation in January 2026.
The manufacturer succeeded in conducting a viable indirect comparison of three studies. The result: For the first time in a benefit assessment for this chronic disease, there is a hint of a considerable added benefit in comparison with berotralstat, one of the three options for the ACT.
Rare hereditary disease
HAE is a rare hereditary disease whose symptoms typically begin in childhood or adolescence. It is characterized by recurrent swelling of the skin or mucous membranes due to a genetic defect that causes a deficiency of an enzyme inhibitor. In healthy people, this inhibitor prevents excessive permeability of the blood vessels. The excessive permeability in HAE leads to too much fluid leaking from the blood vessels into the tissue. The resulting swelling can be potentially fatal, particularly in the respiratory tract. Angioedema in the mucous membrane of the digestive tract is accompanied by severe pain and indigestion.
In addition to acute treatment used to stop attacks as quickly as possible, long-term prevention is an option for patients who experience frequent attacks. For this purpose, concentrates of the missing inhibitor can be injected into the bloodstream. Prophylactic subcutaneous or oral drugs can also be administered to prevent excess fluid from entering the tissue.
From this group of drugs, the Federal Joint Committee (G-BA) specified three possible ACTs, including berotralstat.
Far fewer attacks
Although several active comparator therapies are approved, the manufacturer compared garadacimab with placebo in its randomized controlled trial (RCT). In its dossier, however, it used data from two further RCTs to conduct an indirect comparison between berotralstat and placebo, with the latter serving as the common comparator. Due to the very similar study designs, this indirect comparison was suitable for almost all patient-relevant outcomes.
The number of monthly HAE attacks decreased sharply on garadacimab. Some study participants had no attacks at all during the observation period. There were also small advantages in patient-reported outcomes. Overall, there is a hint of a considerable added benefit.
“For the first time, suitable data are available for a comparison with the appropriate comparator therapy in this therapeutic indication,” says Philip Kranz, Head of the Haemato-Oncology and Infectiology Division of IQWiG’s Drug Assessment Department. “However, we cannot understand why placebo-controlled studies are still being conducted in this therapeutic indication. Several established treatment options have been available for hereditary angioedema for a long time.”
The G‑BA decides on the extent of the added benefit
The dossier assessment is part of the early benefit assessment in accordance with the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After publication of the dossier assessment, the G‑BA conducts a commenting procedure and makes a decision on the extent of the added benefit.