Rare Daily Staff

GlaxoSmithKline reported positive results from the pivotal study of Nucala (mepolizumab) in the treatment of patients living with hypereosinophilic syndrome, making it the first treatment to demonstrate a reduction in flares for this rare disease.

Hypereosinophilic Syndrome (HES) is a rare group of inflammatory disorders that affects approximately 20,000 people globally. Patients with the condition have a persistent and marked overproduction of eosinophils, a type of white blood cell. When eosinophils infiltrate certain tissues, they can cause inflammation and organ damage which, over time, can impact patients’ day-to-day ability to function. Complications can range from fever and malaise to respiratory and cardiac problems. If left untreated, the symptoms of HES become progressively worse and the disease can be life-threatening.

The pivotal phase 3 study, which enrolled 108 patients, is a 32-week, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of subcutaneous mepolizumab every four weeks compared with placebo in adolescent and adult patients with severe HES, defined by at least two HES flares within the past 12 months and a blood eosinophil count of 1000 cells/µL or higher.

The study met its primary endpoint, demonstrating a statistically significant result with 50 percent fewer patients experiencing a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with mepolizumab, compared to placebo, when added to standard of care treatment over the 32-week study period (56 percent vs 28 percent).

Secondary endpoints from the study were also statistically significant and supported the primary endpoint, showing that the risk of first HES flare over the study period was 66 percent lower for patients treated with mepolizumab compared to placebo, and there was a 66 percent reduction in the annualized rate of HES flares versus placebo. The safety results in the study were consistent with the known profile of mepolizumab.

“Mepolizumab has the potential to change the treatment landscape for patients with HES which is a complex and debilitating disease with limited therapeutic options today,” said Hal Barron, chief scientific officer and president of R&D at GSK.

Mepolizumab is a first-in-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils reducing blood eosinophils without completely depleting them. It was first approved in 2015 under the trade name Nucala for severe eosinophilic asthma.

“Mepolizumab is thought to work by reducing blood eosinophil levels and evidence suggests it has potential as a targeted treatment option for a range of inflammatory diseases driven by raised eosinophils,” said Gerald Gleich, allergist, immunologist and HES expert at the University of Utah. “These data are very promising and should provide hope for patients affected by this rare, life-threatening condition caused by eosinophilic inflammation.”

Based on these data, GSK plans to progress regulatory submissions in 2020. Further results from the study will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.

Mepolizumab for HES has received both Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration, and Orphan Drug designation by the European Medicines Agency for the treatment of HES.

Photo: Hal Barron, chief scientific officer and president of R&D at GlaxoSmithKline

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