FDA Grants GSK Priority Review for Nucala to Treat Patients with HES

Rare Daily Staff

The U.S. Food and Drug Administration granted GlaxoSmithKline Priority Review for its application seeking approval of Nucala in the treatment of patients with hypereosinophilic syndrome.

Priority review is granted to drugs that treat a serious condition and if approved would provide a significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. It shortens the time to a decision to six months from the customary 10 months.

If approved, it would make Nucala the first targeted biologic treatment for patients with this rare and life-threatening disease caused by eosinophilic inflammation for which treatment options are currently limited.

Hypereosinophilic Syndrome (HES) is a rare and under-diagnosed disorder, making it difficult to estimate its overall prevalence. Patients with HES 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 feeling ill to respiratory and cardiac problems. If left untreated, the symptoms of HES become progressively worse and the disease can be life-threatening.

First approved in 2015 for severe eosinophilic asthma, Nucala (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 to normal levels. At normal levels eosinophils may play a role in maintaining health.

The application as a treatment for HES is based on positive results from a pivotal phase 3 study, a 32-week, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of subcutaneous mepolizumab every four weeks compared with placebo in adolescent and adult patients with uncontrolled HES. Uncontrolled HES was defined by at least two HES flares (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) within the past 12 months and a blood eosinophil count of 1000 cells/µL or higher at screening.

The study met its primary endpoint, demonstrating a statistically significant result of fewer patients experiencing a HES flare or withdrawal from the study when treated with mepolizumab, compared to placebo, when added to standard of care. All secondary endpoints were statistically significant in favor of mepolizumab compared to placebo.

FDA has previously approved Nucala for use as an add-on maintenance therapy for severe eosinophilic asthma and for the treatment of eosinophilic granulomatosis with polyangiitis and is currently being investigated in several other eosinophil-driven diseases. FDA has also granted both Fast Track and Orphan Drug designations for Nucala as a treatment for HES.