FDA Approves Nucala as the First and Only Biologic Treatment for Hypereosinophilic Syndrome (HES)

• Third US indication for Nucala demonstrates GSK's commitment to finding new ways to help patients with eosinophil-driven diseases

GlaxoSmithKline plc (GSK) (NYSE:GSK) today announced the US Food and Drug Administration (FDA) has approved Nucala (mepolizumab) for the treatment of adult and pediatric patients aged 12 years and older with Hypereosinophilic Syndrome (HES) for ≥ six months without an identifiable non-hematologic secondary cause. The approval makes Nucala the first and only targeted biologic treatment to be approved for patients with this eosinophil-driven disease in the US.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: "HES is a complex, life-threatening condition that impacts nearly 5,000 patients in the US. Today's approval gives these patients access to a biologic treatment for the first time and demonstrates our commitment to maximising Nucala's impact on eosinophil-driven diseases."

The FDA approval follows a priority review of data from a clinical development programme that included positive results from a pivotal phase 3 study, recently published in the Journal of Allergy and Clinical Immunology. The study showed 50 percent fewer patients experienced a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with Nucala, compared to placebo, when added to standard of care treatment over the 32-week study period (28% vs 56%; p=0.002).

According to Dr. Gerald Gleich, MD, allergist, immunologist and a HES expert: "Patients with HES often suffer from debilitating flares of their disease. Reducing them is an important treatment goal. For the first time, we now have a biologic treatment option to offer appropriate patients with this complex disease."

Patients with HES have a persistent and marked overproduction of eosinophils, a type of white blood cell. Reducing the overproduction of eosinophils to normal levels can help people with eosinophil-driven diseases such as HES.

Mary Jo Strobel, Executive Director, American Partnership for Eosinophilic Disorders (APFED) added: "HES can take many years to diagnose and most patients go through a long and frustrating journey that continues even after the diagnosis is confirmed as treatment roadmaps are often unclear and limited. APFED welcomes this approval of Nucala for HES as it gives our community hope."

Nucala is currently used as an add-on maintenance therapy for severe eosinophilic asthma and for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA), and is being investigated in several other eosinophil-driven diseases.

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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. People with HES may have eosinophil levels three times greater than normal. 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 patients aged 12 years and older 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 Nucala (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 26 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.

In a clinical trial in patients with Hypereosinophilic Syndrome, no additional adverse reactions were identified to those reported in the severe asthma trials. Injection site reactions (e.g., burning, itching) occurred in 7% of subjects treated with 300 mg of Nucala versus 4% 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.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and as set out in GSK's Principal risks and uncertainties" section of the Q2 Results and any impacts of the COVID-19 pandemic.

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