GSK’s Nucala Hits the Mark in Phase III HES Trial, Setting Up Potential Approval

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Two months after winning approval from the U.S. Food and Drug Administration as an asthma treatment, GlaxoSmithKline is eying another potential regulatory win for Nucala following positive Phase III results in the treatment of patients living with Hypereosinophilic Syndrome (HES).

In the Phase III study, Nucala (mepolizumab) hit its primary endpoint by demonstrating a statistically significant result with 50% fewer patients experiencing a HES flare, defined as a worsening of symptoms or eosinophil threshold requiring an escalation in therapy, when added to standard of care and compared to placebo. GSK said the results mark Nucala as the first treatment to demonstrate a reduction in flares for this rare disease.

HES is a rare group of inflammatory disorders that affects approximately 20,000 people around the world. Patients who are diagnosed 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.

In its announcement, GSK noted that the Nucala arm also hit multiple secondary endpoints in the trial. GSK said for trial patients treated with Nucala, a risk of first HES flare over the study period was 66% lower than for placebo patients. There was also a 66% reduction in the annualized rate of HES flares versus placebo, GSK said. Fatigue scores also improved for the Nucala-treated patients, the company said. Further results from the study will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications, GSK added.

Based on the data from the Phase III trial, GSK said it will seek regulatory approval for Nucala in this indication next year. In September, Nucala was approved as a treatment for children with severe eosinophilic asthma. The approval made Nucala the only targeted biologic to be approved for the condition in children ages six to 11. Nucala, which targets the IL-5 pathway, was initially approved in 2015 by the FDA to treat patients age 12 years and older with severe asthma with an eosinophilic phenotype.

Nucala for HES has received both Fast Track and Orphan Drug designations by the FDA. The European Medicines Agency has granted Orphan Drug Designation to Nucala for the treatment of HES.

“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,” Hal Barron, GSK’s chief scientific officer and R&D head said in a statement.

Gerald Gleich, an expert in HES from the University of Utah, called the data from the late-stage study “promising” and noted that Nucala works by reducing blood eosinophil levels. Evidence suggests, Gleich continued, that Nucala has potential as a targeted treatment option for a number of inflammatory diseases driven by raised eosinophils.