Experimental drug engasertib shows promise for treating inherited bleeding disorder

Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder worldwide, affecting 1 in 3,800 persons. HHT's hallmark symptom is chronic nosebleeds, which often occur alongside other internal bleeding and vascular malformations that impact quality of life and longevity. A new study from Mass General Brigham tested the safety and efficacy of engasertib, a drug specifically designed to target the condition. This 75-participant, double-blind, placebo-controlled trial found engasertib was safe and decreased nosebleed frequency and duration. Their results are published in New England Journal of Medicine.

"HHT causes serious vascular abnormalities throughout the body, often leading to dangerous, abnormal blood vessels in the brain, lungs, and liver, which bring with them major complications including stroke, heart failure, and brain hemorrhage-yet an FDA-approved treatment doesn't exist," said co-lead principal investigator and first author Hanny Al-Samkari, MD, a Mass General Brigham hematologist and co-director of the Hereditary Hemorrhagic Telangiectasia Center of Excellence at Massachusetts General Hospital. "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."

HHT's impact can be both pervasive and devastating. HHT mutates the activin receptor-like kinase 1 (ALK1) pathway, which normally controls new blood vessel formation and vascular maintenance. With these mutations come an excess of the protein AKT-which is the target of engasertib, an oral, once-daily AKT inhibitor developed by Vaderis Therapeutics.

To test the drug's safety and efficacy, 75 people with HHT were randomly split into three treatment groups to take 30 milligrams of engasertib, 40 milligrams of engasertib, or placebo once daily for 12 weeks. The trial was sponsored by Vaderis Therapeutics and was designed by the sponsor in collaboration with the investigators.

At the end of 12 weeks, patients who received engasertib experienced fewer and shorter nosebleeds relative to the placebo group. Additionally, 61% of the 40-milligram group and 37% of the 30-milligram group reported feeling "much better" at the end of 12 weeks, while only 27% of the placebo group said the same. The drug was deemed safe, with the most common side effect being a mild and reversible rash and serious adverse events not differing significantly between treatment and placebo groups. The trial positions engasertib as a potential future treatment for patients with HHT, but bigger, longer studies are still needed to validate the findings.