Repurposed Drug Shows Promise for Treating Rare Eosinophilic Diseases

NIAID Now | May 22, 2018

Eosinophils normally comprise a small portion of the body’s white blood cell population and help mediate inflammation and fight parasitic infections. Elevated levels of these cells can lead to serious health problems, including hypereosinophilic syndromes (HES)—rare, chronic and sometimes life-threatening disorders in which very high numbers of eosinophils are present in the blood and tissues. 

Earlier this month, scientists from NIAID and Knopp Biosciences reported that dexpramipexole, a drug initially developed to treat neurological diseases, benefited a subset of patients with HES. Their findings, published online in the journal Blood, help lay the groundwork for a larger clinical trial to further evaluate this potential new HES treatment.

There are many different types of HES, and symptoms can vary depending on the organs involved and the severity of the disease. People with HES commonly experience fatigue, muscle and joint pains, rashes, itching, abdominal pain, shortness of breath and cough. Potentially life-threatening cardiac and neurologic complications occur in up to 20 percent of people with HES.

Drugs called glucocorticoids (steroids) are the standard treatment for almost all variants of HES. While glucocorticoids initially reduce eosinophil counts in many people with HES, the drugs may become less effective at controlling eosinophil levels over time. In addition, glucocorticoids have serious side effects, including bone loss, fractures, weight gain and depression. Thus, scientists are investigating treatment alternatives that could reduce or eliminate the need to take glucocorticoids.

Dexpramipexole was originally investigated as a potential treatment for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Despite promising results in early clinical studies, a Phase 3 clinical trial in ALS did not meet its primary efficacy endpoint. However, the investigators noted that the drug greatly decreased eosinophil levels among the study participants. Researchers shifted gears and began studying dexpramipexole as a potential treatment for HES and other disorders characterized by high eosinophil levels.

The recent Phase 2 study at the NIH Clinical Center, led by NIAID’s Amy Klion, M.D., enrolled 10 participants with HES who required a moderate to high dose of glucocorticoids to control their disease. Prior to starting dexpramipexole treatment, the participants underwent a gradual reduction in their glucocorticoid doses to determine the minimally effective dose needed to control their HES. They then took dexpramipexole orally twice a day for 12 weeks, while continuing a standard dose of glucocorticoids. After 12 weeks, researchers again determined the minimally effective dose of glucocorticoids needed to control each participant’s disease.

Four out of the 10 participants had a greater than 50 percent decrease in their minimally effective glucocorticoid dose after 12 weeks of dexpramipexole. Notably, three of these four participants were able to completely discontinue their glucocorticoids, and they remained asymptomatic and eosinophil-free for 13 to 32 months while continuing dexpramipexole treatment. Overall, dexpramipexole was well-tolerated among the study participants. Reported adverse events were mild and did not cause any participants to stop taking the drug.

The researchers now are planning a multi-site Phase 3 clinical trial to assess the long-term safety and efficacy of dexpramipexole in HES and to evaluate the drug’s mechanism.

May 20-26, 2018, is National Eosinophil Awareness Week.


SR Panch et al. Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes. Blood DOI: 10.1182/blood-2018-02-835330 (2018).

For more information about NIAID research on HES, see Dr. Klion’s lab page.


Content last reviewed on May 22, 2018