Engasertib shows promise in hereditary haemorrhagic telangiectasia

In the treatment of patients with hereditary haemorrhagic telangiectasia (HHT), use of the novel allosteric, selective AKT inhibitor engasertib appears to be safe and reduce the frequency and duration of epistaxis, according to a proof-of-concept study.

A total of 75 patients with HHT were randomly assigned to receive engasertib at 30 (n=24) or 40 mg (n=25) or placebo (n=26), administered orally once daily for 12 weeks. The frequency and severity of adverse events were assessed as the primary outcome, while the frequency of duration of epistaxis were evaluated as the key secondary outcome.

Among the patients who received at least one dose of the trial drug, the most common on-target adverse events associated with engasertib were mild-to-moderate rash (21 percent in the 30-mg group, 42 percent in the 40-mg group, and 8 percent in the placebo group) and mild-to-moderate hyperglycaemia (12 percent in the 40-mg group and 0 percent in the other two groups). These adverse events were reversible. The incidence of serious adverse events was similar across the three treatment groups.

From baseline to week 12, epistaxis frequency dropped by 26.5 percent with 30-mg engasertib, 27.8 percent with 40-mg engasertib, and 18 percent with placebo. Epistaxis duration decreased by 29.9 percent, 41.4 percent, and 23.8 percent, respectively.

The open-label phase of the study is ongoing.