New York: While researchers found sufficient evidence that a drug used to treat bone marrow cancer and Kaposi’s sarcoma is safe and effective in treating hereditary hemorrhagic telangiectasia (HHT), a rare bleeding disorder that affects 1 in 5,000 people worldwide, Then they decided to end it. An early clinical trial funded by the National Institutes of Health (NIH).
The New England Journal of Medicine published the results of the trial, which showed that patients with HHT who were given the drug pomalidomide had a significant reduction in the severity of nosebleeds, required fewer blood transfusions and iron infusions than HHT often requires, and improved quality of life. Good quality.
“It’s very unusual to find a therapeutic agent that works in a rare disorder, so this is a real success story,” said Andrey Kindzelski, MD, Ph.D., of NIH’s National Heart, Lung, and Blood Institute. “Prior to our trial, there was no reliable therapeutic to treat people with HHT. This discovery will give people suffering from this disease a positive outlook and a better quality of life.”
HHT, also known as Osler-Weber-Rendu syndrome, is characterized by severe defects in the way the body’s blood vessels form. Instead of growing linearly, they become unusually tangled and twisted. Disrupted blood vessels are fragile and prone to leaking, causing excessive epistaxis or bleeding along the gastrointestinal tract and other mucosal surfaces. These bleeding episodes, which worsen with age, can lead to anemia and reduced quality of life. In severe cases, they can be life-threatening.
Current options for treating HHT include closing off the offending blood vessels in the nose and gastrointestinal tract, or prescribing off-label medications that temporarily stabilize blood clots at bleeding sites, which in turn reduces bleeding. There are currently no Food and Drug Administration-approved medications for the long-term management of HHT.
The researchers hypothesized that pomalidomide works by blocking the growth of abnormal blood vessels. It can cause blood vessel structures to become more normal or have thicker walls so that they are less fragile. However, the research team, led by Keith McCrae, a professor of molecular medicine at the Cleveland Clinic, says more studies are needed.
Researchers enrolled 144 adults with HHT at 11 US medical centers between November 5, 2019 and June 27, 2023. All participants had moderate to severe epistaxis requiring iron infusion or blood transfusion. The researchers gave 95 participants 4 mg of pomalidomide per day, although the dose was reduced to 3 mg or 2 mg per day in patients with adverse reactions—mostly constipation, rash, and lower than average white blood cell counts. The remaining 49 patients received a daily sugar pill that looked like a pomalidomide pill, in addition to their usual care.
At the start of the trial, researchers used a validated HHT-specific bleeding assessment tool to score the severity of each patient’s nosebleeds. To establish a baseline in other areas, participants self-reported other data throughout the trial, particularly the severity of their nosebleeds and the impact of their HHT symptoms on daily activities using a special scoring system. The number of red blood cell units was also recorded.
In June 2023, 43 months into the scheduled four-year trial, an interim analysis found that pomalidomide met prespecified thresholds for efficacy, and the trial was closed to further enrollment.
“These findings have broad implications for people with more severe forms of HHT,” Kindzelski said. “In those cases, malformed blood vessels can develop in organs such as the lungs, liver and brain, leading to hemorrhagic stroke, bleeding in the lungs or heart failure. Such treatment can be life-saving for such patients.”
Although the researchers did not follow the participants after the trial ended, McCree noted that some of his patients from the study went four to six months without a recurrence of nosebleeds even after they stopped the medication. This suggests that the drug may hold promise as a long-term or intermittent treatment. (ANI)
