New Drug Engasertib Shows Real Promise for Treating Hereditary Hemorrhagic Telangiectasia
A new clinical study has brought encouraging news for people living with Hereditary Hemorrhagic Telangiectasia (HHT), a genetic bleeding disorder that currently has no FDA-approved treatment. Researchers from Mass General Brigham have reported that an experimental drug called engasertib was both safe and effective in reducing the frequency and duration of chronic nosebleeds, the most common and disruptive symptom of the condition.
The findings were published in The New England Journal of Medicine, one of the world’s most respected medical journals, marking a significant milestone for HHT research and treatment development.
Understanding Hereditary Hemorrhagic Telangiectasia and Why It Matters
Hereditary Hemorrhagic Telangiectasia is the second most common inherited bleeding disorder worldwide, affecting approximately one in every 3,800 people. Despite being relatively common for a rare disease, HHT remains widely underdiagnosed and misunderstood.
The condition is caused by genetic mutations that interfere with normal blood vessel development. As a result, patients develop fragile and abnormal blood vessels, known as telangiectasias and arteriovenous malformations (AVMs). These malformed vessels can rupture easily, leading to frequent bleeding episodes.
The most recognizable symptom of HHT is chronic nosebleeds, often starting in childhood and worsening with age. However, the disease is far more than a nosebleed disorder. Many patients also develop abnormal blood vessels in the lungs, brain, liver, and gastrointestinal tract, which can lead to serious complications such as stroke, heart failure, severe anemia, and brain hemorrhage. These complications can significantly reduce both quality of life and life expectancy.
Until now, treatment options have focused on managing symptoms, such as cauterizing blood vessels or giving iron infusions and blood transfusions. There has been no medication designed to directly target the underlying biology of HHT.
What Is Engasertib and How Does It Work?
Engasertib is an oral, once-daily medication developed by Vaderis Therapeutics. It belongs to a class of drugs known as AKT inhibitors.
To understand why this matters, it helps to look at the biology of HHT. Most cases of HHT involve mutations in genes related to the ALK1 signaling pathway, which normally regulates how blood vessels form and repair themselves. When this pathway is disrupted, the body produces excess AKT protein activity, contributing to the formation of abnormal and fragile blood vessels.
Engasertib works by inhibiting AKT, helping to rebalance this disrupted signaling pathway. In simple terms, the drug aims to address the root cause of abnormal blood vessel growth, rather than just treating the bleeding after it occurs.
Inside the Clinical Trial Design
The study was a randomized, double-blind, placebo-controlled clinical trial, which is considered the gold standard for evaluating new treatments.
A total of 75 adults with confirmed HHT participated in the trial. They were randomly assigned to one of three groups:
- 30 milligrams of engasertib once daily
- 40 milligrams of engasertib once daily
- Placebo
The treatment period lasted 12 weeks. Neither the participants nor the researchers knew who was receiving engasertib or placebo until the study was completed, ensuring unbiased results. The trial was sponsored by Vaderis Therapeutics and designed in collaboration with the study investigators.
The primary goals were to evaluate safety and changes in nosebleed frequency and duration, along with patient-reported quality-of-life outcomes.
Key Results From the Engasertib Trial
At the end of the 12-week period, the results were clear and encouraging.
Participants who received engasertib experienced fewer nosebleeds and shorter bleeding episodes compared with those who received placebo. The improvements were seen in both dosing groups, with the 40-milligram dose showing the strongest effects.
Patient-reported outcomes added another important layer of insight. By the end of the study:
- 61% of patients taking 40 mg of engasertib said they felt much better
- 37% of patients taking 30 mg reported feeling much better
- Only 27% of patients in the placebo group reported similar improvement
These findings suggest that engasertib not only reduced measurable bleeding but also made a meaningful difference in how patients felt day to day.
Safety and Side Effects Observed in the Study
Safety was a critical focus of the trial, especially given that engasertib targets a key cellular signaling pathway.
The drug was found to be generally safe and well tolerated. The most common side effect was a mild and reversible skin rash. Importantly, serious adverse events were not significantly different between the engasertib groups and the placebo group.
No new or unexpected safety concerns emerged during the 12-week trial, which is an essential step before moving into larger and longer studies.
Why This Study Is a Big Deal for HHT Patients
For people living with HHT, this trial represents something that has been missing for decades: a targeted drug designed specifically for their disease.
HHT patients often deal with daily or weekly nosebleeds, chronic fatigue from anemia, repeated medical procedures, and constant concern about internal bleeding. Even modest reductions in bleeding can lead to fewer hospital visits, less need for transfusions, and a better overall quality of life.
Engasertib stands out because it is not a general bleeding medication but a drug that directly targets the molecular pathway driving HHT. That makes it a strong candidate for becoming the first disease-modifying therapy for this condition.
What Comes Next for Engasertib?
While the results are promising, researchers emphasize that larger and longer clinical trials are still needed. The current study was relatively short and involved a limited number of participants.
Future studies will aim to confirm these findings, evaluate long-term safety, and explore whether engasertib can also reduce internal bleeding and organ-related complications, not just nosebleeds.
If those trials are successful, engasertib could move closer to regulatory approval and eventually become a standard treatment option for HHT patients worldwide.
Research Reference
Engasertib versus Placebo for Bleeding in Hereditary Hemorrhagic Telangiectasia, The New England Journal of Medicine (2025)
https://www.nejm.org/doi/10.1056/NEJMoa2504411
