Vaderis drug lends hope to patients with bleeding disease HHT

A clinical trial of Vaderis Therapeutics' AKT inhibitor engasertib suggests it could be the first effective treatment for hereditary haemorrhagic telangiectasia (HHT), the second most common inherited bleeding disorder.

People living with HHT have blood vessels that have not developed properly, known as arteriovenous malformations (AVMs), and suffer symptoms like regular and persistent nosebleeds, red spots on the body, and anaemia.

In some cases, the AVMs can form in organs like the lungs, liver, and brain, leading to low blood oxygen levels and even more serious complications like seizures and strokes. HHT, also known as Osler-Weber-Rendu syndrome, affects 1 in 3,800 persons worldwide, but has no approved therapies anywhere in the world.

Researchers tested engasertib in a 75-patient study that compared two doses of the oral drug (30 mg or 40 mg once daily) to placebo over 12 weeks.

According to the results – which have just been published in the New England Journal of Medicine – the AKT inhibitor achieved a reduction in nosebleed frequency of around 27%, compared to an 18% reduction in the control group.

Meanwhile, the duration of nosebleeds was cut by around 30% with 30 mg engasertib, 41% with the 40 mg dose, and 24% with placebo. The drug was generally well tolerated, with mild-to-moderate rash the most common side effect.

Overall, 61% of the 40 mg group and 37% of the 30 mg group reported feeling "much better" at the end of 12 weeks, while only 27% of the placebo group said the same.

"This engasertib trial is a step toward a better life for these patients, and I'm thrilled we found it to be both safe and effective at decreasing bleeding in HHT," said lead investigator Dr Hanny Al-Samkari of Massachusetts General Hospital in the US.

In HHT, there is thought to be an activation in the activin receptor-like kinase 1 (ALK1) pathway, which normally controls new blood vessel formation and vascular maintenance, leading to excessive production of AKT. The data with engasertib provides proof-of-concept for using AKT inhibitors to tackle that excess and reduce HHT symptoms.

Swiss biotech Vaderis reported the topline findings from the study in August, and is now discussing the design of a possible pivotal trial of engasertib with major health authorities. It also said an open-label extension of the trial had shown some patients were continuing to see a benefit from the drug out to six months.

Last week, Basel-based Vaderis was granted fast-track status for engasertib for the treatment of HHT.

Photo by Velizar Ivanov on Unsplash