FDA grants priority review of Nucala for patients with Hypereosinophilic Syndrome

GlaxoSmithKline (GSK) announced that the US Food and Drug Administration (FDA) has granted a priority review for the company’s application seeking approval of Nucala (mepolizumab) in the treatment of patients with Hypereosinophilic Syndrome (HES) in the US.

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

FDA has also granted both Fast Track and Orphan Drug designations for the use of Nucala in HES. These designations are often given to treatments that have the potential to address a high unmet need in patients with rare diseases.

The application is based on positive results from a pivotal phase 3 study that 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 favour 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 (EGPA). Nucala is currently being investigated in several other eosinophil-driven diseases. It is not yet approved for use in HES anywhere in the world.

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 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, was a 32-week, randomised, double-blind, placebo-controlled study to investigate the efficacy and safety of subcutaneous mepolizumab 300mg (3×100) 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.

First approved in 2015 for severe eosinophilic asthma (SEA), mepolizumab is the 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.

Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 3,000 patients in 21 clinical trials across a number of eosinophilic indications and has been approved under the brand name Nucala in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with SEA. It is approved for paediatric use in SEA from ages six to 17 in Europe and the US and several other markets. In the US, Japan, Canada and a number of other markets, it is approved for use in adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Regulatory submissions for chronic rhinosinusitis with nasal polyps (CRSwNP) are expected to progress in 2020. Mepolizumab is currently being investigated in COPD. It is not currently approved for use in CRSwNP or COPD anywhere in the world.