Andexanet alfa for haemorrhages: hopes not fulfilled

If life-threatening or uncontrollable haemorrhage occurs during treatment with an anticoagulant, the effect of the anticoagulant must be reversed as quickly as possible. The drug andexanet alfa was made available for reversal of anticoagulation with rivaroxaban or apixaban in 2019 and was considered promising at the time. However, no comparative study data were available for the initial early benefit assessment, so the conclusion was: added benefit not proven. The Federal Joint Committee (G-BA) reached a temporary resolution. Following the expiry of the temporary resolution, the drug manufacturer has now submitted a new dossier, this time containing informative data from a study initiated by the European Medicines Agency (EMA).

The study predominantly included people with intracerebral haemorrhage. In the comparator arm, any treatment other than andexanet alfa was allowed, which concurred with the appropriate comparator therapy (individualized treatment). Based on these study data, the Institute for Quality and Efficiency in Health Care (IQWiG) sees a hint of a lesser benefit of andexanet alfa versus the comparator therapy. The (German-language) report was published in October 2025, an English translation in June 2026.

Primary study outcome not relevant for the benefit assessment

„The manufacturer found positive effects in the primary outcome of its study, but this outcome did not have an informative value for the benefit assessment,“ explains Daniela Preukschat, Division Head of the IQWiG Drug Assessment Department. The primary outcome was effective haemostasis, for which several criteria had to be met. These included a haematoma expansion of no more than 35 per cent 12 hours after randomization, and an increase of no more than 6 points in the so-called NIHSS score, which is used for the early detection of strokes. “Regarding the threshold for haematoma expansion, its relevance to patients is unclear because there is no convincing data that it is a validated surrogate outcome for e.g. long-term impairment.”

However, there are hints of greater harm, in some cases of major extent, in several serious side effects such as cardiac disorders, thrombotic events and ischaemic stroke. “The relevance of these side effects to patients is beyond question,” says Daniela Preukschat. “This leads to the only conclusion that andexanet alfa for intracerebral haemorrhages has a lesser benefit than standard treatment.”

G-BA decides on the extent of 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.