FDA grants priority review of Nucala for patients with Hypereosinophilic Syndrome (HES)

For media and investors only

Issued: London, UK

An approval would give Nucala a third indication in an eosinophil-driven disease

GlaxoSmithKline plc (GSK) today 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.

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About Hypereosinophilic Syndrome (HES)
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.

About the phase 3 study
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 (3x100) 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.

About mepolizumab
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.

Mepolizumab is not approved for the relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

Important safety information
The following information is based on the US Prescribing Information for Nucala in licensed indications only. Please consult the full Prescribing Information for all the labelled safety information for Nucala.

CONTRAINDICATIONS
Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

WARNINGS AND PRECAUTIONS

• Hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after administration of Nucala. Discontinue
• Nucala in the event of a hypersensitivity reaction.
• Do not use to treat acute bronchospasm or status asthmaticus.
• Herpes zoster infections have occurred in patients receiving Nucala. Consider vaccination if medically appropriate.
• Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with Nucala. Decrease corticosteroids gradually, if appropriate.
• Treat patients with pre-existing helminth infections before therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue Nucala until parasitic infection resolves.

ADVERSE REACTIONS
Most common adverse reactions (incidence ≥5%) in severe asthma clinical trials included headache, injection site reaction, back pain, and fatigue. Injection site reactions (eg, pain, erythema, swelling, itching, burning sensation) occurred in 8% of subjects treated with 100 mg of Nucala versus 3% treated with placebo.

In a clinical trial in patients with EGPA receiving 300 mg of Nucala, no additional adverse reactions were identified to those reported in severe asthma clinical trials. Injection site reactions (eg, pain, erythema, swelling) occurred in 15% of subjects treated with 300 mg of Nucala versus 13% treated with placebo.

GSK’s commitment to respiratory disease
For over 50 years, GSK has led the way in developing medicines that advance the management of asthma and COPD. From introducing the world’s first selective short-acting beta agonist in 1969, to launching six treatments in five years to create today’s industry-leading respiratory portfolio, we continue to innovate so we can reach the right patients, with the right treatment. Working together with the healthcare community, we apply world-class science to discover and understand the molecules that become the medicines of tomorrow. We won’t stand still until the simple act of breathing is made easier for everyone.

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.