Engasertib Shows Promise in First Controlled Trial for Hereditary Hemorrhagic Telangiectasia
Key Insights
A 75-participant, double-blind, placebo-controlled trial found that engasertib (search), an oral AKT inhibitor (search), safely reduced nosebleed frequency and duration in patients with hereditary hemorrhagic telangiectasia (search) (HHT (search)).
The study represents a significant advance for HHT (search), the second most common inherited bleeding disorder (search) affecting 1 in 3,800 people worldwide, which currently has no FDA-approved treatments.
Patients receiving the 40-milligram dose showed the strongest response, with 61% reporting feeling "much better" compared to only 27% in the placebo group after 12 weeks of treatment.
A new experimental drug has demonstrated promising results in treating hereditary hemorrhagic telangiectasia (search) (HHT (search)), offering hope for patients with this inherited bleeding disorder (search) that currently lacks FDA-approved therapies. The 75-participant, double-blind, placebo-controlled trial of engasertib (search) showed significant reductions in nosebleed frequency and duration while maintaining a favorable safety profile.
The study, published in the New England Journal of Medicine and led by Mass General Brigham (search) researchers, represents a potential breakthrough for HHT (search) patients who face serious vascular complications including stroke (search), heart failure (search), and brain hemorrhage (search).
Addressing an Unmet Medical Need
HHT (search) affects 1 in 3,800 people worldwide, making it the second most common inherited bleeding disorder (search). The condition's hallmark symptom is chronic nosebleeds, which often occur alongside other internal bleeding and vascular malformations that significantly impact quality of life and longevity.
"HHT (search) 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 (search), heart failure (search), and brain hemorrhage (search)—yet an FDA-approved treatment doesn't exist," said co-lead principal investigator and first author Hanny Al-Samkari, MD, a Mass General Brigham (search) hematologist and co-director of the Hereditary Hemorrhagic Telangiectasia (search) Center of Excellence at Massachusetts General Hospital.
Targeting the Root Cause
HHT (search) results from mutations in the activin receptor-like kinase 1 (search) (ALK1) pathway, which normally controls new blood vessel formation and vascular maintenance. These mutations lead to an excess of the protein AKT (search), creating the therapeutic target for engasertib (search), an oral, once-daily AKT inhibitor (search) developed by Vaderis Therapeutics (search).
Trial Design and Results
The 12-week study randomly assigned 75 HHT (search) patients to three treatment groups: 30 milligrams of engasertib (search), 40 milligrams of engasertib, or placebo, all taken once daily. The trial was sponsored by Vaderis Therapeutics (search) and designed collaboratively between the sponsor and investigators.
After 12 weeks of treatment, patients receiving engasertib (search) experienced fewer and shorter nosebleeds compared to the placebo group. The higher dose showed particularly encouraging results, with 61% of patients in the 40-milligram group reporting feeling "much better" at the study's conclusion, compared to 37% in the 30-milligram group and only 27% in the placebo group.
Safety Profile
The drug demonstrated a favorable safety profile throughout the trial period. The most common side effect was a mild and reversible rash, and serious adverse events did not differ significantly between treatment and placebo groups.
"This engasertib (search) 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 (search)," Al-Samkari noted.
Path Forward
While the results position engasertib (search) as a potential future treatment for HHT (search) patients, researchers emphasize that larger, longer studies are still needed to validate these initial findings and establish the drug's long-term efficacy and safety profile. The successful completion of this proof-of-concept trial marks an important milestone in developing the first targeted therapy for this challenging inherited bleeding disorder (search).