Sledding with her grandchildren. Getting in a workout at the gym. Sitting in a pew at church. Going shopping with her husband.
These may seem like routine daily tasks, but Kerry Pare, 62, doesn’t take any of these moments for granted.
It wasn’t long ago that the joy and peace she finds in these simple activities was often out of reach—she didn’t have the energy for playing or working out and everywhere she went, she had to bring a full roll of paper towels with her in case a sudden and extreme nosebleed interrupted daily life.
“I remember sitting in the front pew at church, and boom—a nosebleed. Everyone came running, and it’s just so embarrassing and so disruptive,” she recalls. “Wherever I was, I just knew it could happen at any time and it wouldn’t stop.”
Severe and recurrent nosebleeds are one of the most visible and distinct symptoms of a genetic condition known as hereditary hemorrhagic telangiectasia (HHT).
Other symptoms include telangiectasis—small red dots that can appear on the face, lips, tongue, and fingers—and fatigue, caused by chronic blood loss.
People with HHT have multiple arteriovenous malformations (AVMs), or abnormal blood vessel connections, which can cause sudden bleeding in the nose, GI tract and other organs.
Unlike other genetic conditions which cause distinct symptoms in early life, the symptoms of HHT can be mild in young patients and might be dismissed.
But they become more severe with age and can cause serious and fatal complications in vital organs including the brain, lung, liver and GI tract.
Hanny Al-Samkari, MD
“This is a severe disease that often dramatically reduces a person’s quality of life and unfortunately may take their life,” says Hanny Al-Samkari, MD, a Mass General Brigham hematologist and co-director of the Hereditary Hemorrhagic Telangiectasia Center of Excellence at Massachusetts General Hospital.
As a clinical investigator, Al-Samkari is searching for better treatments for patients like Kerry.
“There are currently no FDA-approved treatments for HHT," Samkari says. “This is an area where we can do a lot of good and really make a difference in people's lives.”
Searching for Answers
HHT is an inherited disease, which means that many of Kerry’s family members have the condition, too.
Kerry first learned about HHT about two decades ago when she brought her daughter, who had been spitting up blood, into the doctor's office. At first, her doctor wasn’t sure what was causing the child’s symptoms—or the mother’s. They were referred to genetic specialists at Massachusetts General Hospital, who were able to tell just from a physical exam and family history that both mother and daughter had HHT.
“They took one look, and they knew right away,” Kerry says.
The Mass General HHT Center is a designated Center of Excellence and its physicians care for more than 500 families with the condition. The center provides treatment, support, and education for its patients, and it also offers them access to clinical trials, which test new treatments for HHT.
“We want to give our patients the best chance for the best possible outcome,” said Al-Samkari. “How can we improve and lengthen their lives? And how can we make things better for their children so that HHT doesn’t affect the next generation as it has this one?”
Quest for Better Treatments
For decades, HHT management was limited to surgical procedures. Surgeons would surgically remove abnormal blood vessels from a patient’s lungs or brain. They would cauterize bleeding lesions, but those lesions would almost invariably return, leading to a never-ending cycle of painful procedures.
For nosebleeds, one of the few treatments available was a procedure that sealed off a person’s nostrils, closing them surgically, but this often resulted in blood flowing down the back on their throat instead.
“The word I’d use for this procedure is draconian,” said Al-Samkari. “And that was the state we were in just 10 years ago.”
The field has made significant strides since then. Over the last 10 years, cancer drugs have been repurposed to treat people with HHT, with some success. Al-Samkari’s team published results of a clinical trial testing a repurposed drug last year.
“Repurposed drugs have been helpful, but they can have a high burden of side effects,” he explains. “And they’re used off label, which means they often aren’t covered by insurance.”
Clinical Trials Provide a Lifeline to HHT Patients
This year marked a major milestone in the search for new treatments for HHT: For the first time, a drug specifically designed to treat the condition was tested in a clinical trial, which was co-led by Al-Samkari.
The drug, known as engasertib, met its primary endpoint, significantly reducing the number of and severity of nosebleeds that study participants experienced.
Kerry was among the participants in the trial, and she continues to take the drug as part of its open-label extension.
“When I was invited to participate in the trial, I was napping three to four hours a day,” she says. “I couldn’t watch my grandkids. I couldn't play with them. I’d clean the house and have to go back to bed. It was no way to live.”
For Kerry, the clinical trial was lifechanging.
“Today, I go to the gym five days a week—I’ve got muscles! I play all day with my grandkids and take just a little cat nap to refresh up. What a tremendous difference.”
Al-Samkari is thrilled by the difference Kerry and other patients are experiencing and grateful for their help in advancing the field by taking part in clinical trials.
While the phase 1/phase 2 proof-of-concept trial of engasertib is complete, larger studies will be need before FDA approval. The next step will be a phase 3 trial of the HEROIC study, which the pharmaceutical company Vaderis Therapuetics plans to initiate in 2026.
“I cannot overemphasize the importance of clinical trials for many diseases, but specifically in HHT,” Al-Samkari says. “Clinical trials are an absolute lifeline for these patients. They afford patients the opportunity to receive cutting-edge care that can have a life-changing impact."
"While our mission with these trials is always to provide the best treatment for the patients enrolling in the trials themselves, many patients also tell me that they want to do this to help their kids or siblings or their nieces and nephews and other future patients.”
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