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The trial results, which were published in the New England Journal of Medicine, detail how patients with hereditary hemorrhagic telangiectasia given the drug, called pomalidomide, experienced a significant reduction in the severity of nosebleeds, needed fewer of the blood transfusions and iron infusions that HHT often demands, and showed improved quality of life.

“Finding a therapeutic agent that works in a rare disorder is highly uncommon, so this is a real success story,” said Andrei Kindzelski, M.D., Ph.D., of NIH’s National Heart, Lung, and Blood Institute. “Before our trial, there was no reliable therapeutic to treat people with hereditary hemorrhagic telangiectasia. This discovery will give people who suffer with this disease a positive outlook and better quality of life.”

Current options to treat hereditary hemorrhagic telangiectasia involve closing off the malformed blood vessels in the nose and gastrointestinal tract or prescribing off-label medications that temporarily stabilize blood clotting at sites of bleeding vessels, which in turn reduces bleeding. There are currently no Food and Drug Administration-approved medications for long-term management of hereditary hemorrhagic telangiectasia.

Researchers speculated that pomalidomide worked by blocking the growth of abnormal blood vessels. It may cause the blood vessels to have a more normal structure or thicker walls so they are less fragile. However, the research team, led by Keith McCrae, M.D., professor of molecular medicine at the Cleveland Clinic, says further study will be needed.

Researchers enrolled 144 adults with hereditary hemorrhagic telangiectasia at 11 U.S. medical centers between Nov. 5, 2019, and June 27, 2023. All participants had moderate to severe nosebleeds requiring iron infusions or blood transfusions. Researchers gave 95 of the participants 4 mg of pomalidomide daily, though the dosage was reduced to 3 mg or 2 mg daily in patients with adverse reactions – mostly constipation, rashes, and lower than average white blood cell counts. The remaining 49 patients received a daily sugar pill designed to look exactly like the pomalidomide pill, in addition to their usual care

At the start of the trial, researchers used a validated hereditary hemorrhagic telangiectasia -specific bleeding assessment tool to score each patient’s nosebleed severity. To establish a baseline in other areas, participants self-reported other data throughout the trial, particularly the severity of their nosebleeds and the effect of their hereditary hemorrhagic telangiectasia symptoms on everyday activities using a special scoring system. The number of units of red blood cells transfused or iron infused was also recorded.

In June 2023, 43 months into the scheduled four-year trial, an interim analysis found pomalidomide had met a prespecified threshold for efficacy, and the trial was closed to further enrollment.

“These findings have broader implications for people with more severe forms of hereditary hemorrhagic telangiectasia,” said Kindzelski. “In those cases, malformed blood vessels can develop in organs such as the lung, liver, and brain, which can lead to hemorrhagic stroke, bleeding in the lungs, or heart failure. A treatment like this could be lifesaving for such patients.”

Reference: Al-Samkari, H., Kasthuri, R. S., Iyer, V. N., Pishko, A. M., Decker, J. E., Weiss, C. R., Whitehead, K. J., & McCrae, K. R. (2024). Pomalidomide for epistaxis in hereditary hemorrhagic telangiectasia. New England Journal of Medicine, 391(12), 1015-1027. https://doi.org/10.1056/NEJMoa2312749