GlaxoSmithKline plc (GSK) today announced positive results from the pivotal study of Nucala (mepolizumab) in the treatment of patients living with Hypereosinophilic Syndrome (HES), making it the first treatment to demonstrate a reduction in flares for this rare disease.
The phase 3 study met its primary endpoint, demonstrating a statistically significant result with 50% fewer patients experiencing a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with mepolizumab, compared to placebo, when added to standard of care treatment over the 32-week study period (56% vs 28%; p=0.002).
Dr Hal Barron, Chief Scientific Officer and President, R&D, GSK, said: “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.”
Secondary endpoints from the study were also statistically significant and supported the primary endpoint, showing:
- Risk of first HES flare over the study period was 66% lower for patients treated with mepolizumab compared to placebo (hazard ratio 0.34; 95% CI 0.18, 0.67).
- There was a 66% reduction in the annualised rate of HES flares versus placebo (rate ratio 0.34; 95% CI 0.19, 0.63).
- Fatigue scores improved in mepolizumab compared to placebo (p=0.036).
- The safety results in the study were consistent with the known profile of mepolizumab.
Dr Gerald Gleich, MD, allergist, immunologist and HES expert, University of Utah, said: “Mepolizumab is thought to work by reducing blood eosinophil levels and evidence suggests it has potential as a targeted treatment option for a range of inflammatory diseases driven by raised eosinophils. These data are very promising and should provide hope for patients affected by this rare, life-threatening condition caused by eosinophilic inflammation”.
Based on these data, GSK plans to progress regulatory submissions in 2020. Mepolizumab is not approved for use in HES anywhere in the world. Further results from the study will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.
About Hypereosinophilic Syndrome (HES)
HES is a rare group of inflammatory disorders that affects approximately 20,000 people globally. Patients 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.
About the phase 3 study
The pivotal phase 3 study, which enrolled 108 patients, is 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 severe HES. Severe HES was defined by at least two HES flares within the past 12 months and a blood eosinophil count of 1000 cells/µL or higher. Mepolizumab for HES has received both Fast Track and Orphan Drug designations by the US Food and Drug Administration (FDA). The European Medicines Agency (EMA) has granted Orphan Drug Designation to mepolizumab for the treatment of HES.
First approved in 2015 for severe eosinophilic asthma, 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 without completely depleting them.
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 severe eosinophilic asthma (SEA). It is approved for paediatric use from ages six to 17 in Europe and the US in severe eosinophilic asthma. In the US, Japan and Canada and a number of other markets, it is approved as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis (EGPA). In addition to HES, it is currently being investigated for nasal polyposis and COPD.
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.
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 following administration of Nucala. These reactions generally occur within hours of administration but in some instances can have a delayed onset (i.e. days). In the event of a hypersensitivity reaction, Nucala should be discontinued.
Acute Asthma Symptoms or Deteriorating Disease
Nucala should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Opportunistic Infections: Herpes Zoster
In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred in subjects treated with Nucala compared to none in placebo. Consider varicella vaccination if medically appropriate prior to starting therapy with Nucala.
Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Parasitic (Helminth) Infection
It is unknown if Nucala will influence a patient’s response against parasites. Treat patients with pre-existing helminth infections before initiating therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue treatment with Nucala until infection resolves.
The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of two clinical trials with Nucala (and placebo) were: headache, 19% (18%); injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5% (4%); influenza, 3% (2%); urinary tract infection 3% (2%); abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3% (<1%); and muscle spasm, 3% (<1%).
Systemic Reactions, including Hypersensitivity Reactions: In 3 clinical trials, 3% of subjects who received Nucala experienced systemic (allergic and nonallergic) reactions compared to 5% in the placebo group. Systemic allergic/hypersensitivity reactions were reported by 1% of subjects who received Nucala compared to 2% of subjects in the placebo group. Manifestations included rash, pruritus, headache, and myalgia. Systemic nonallergic reactions were reported by 2% of subjects who received Nucala and 3% of subjects in the placebo group. Manifestations included rash, flushing, and myalgia. A majority of the systemic reactions were experienced on the day of dosing. Reports of anaphylaxis have been received postmarketing.
Injection site reactions (e.g. pain, erythema, swelling, itching, burning sensation) occurred at a rate of 8% in subjects treated with Nucala compared with 3% in subjects treated with placebo.
USE IN SPECIFIC POPULATIONS
The data on pregnancy exposures from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are progressively transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a foetus are likely to be greater during the second and third trimesters of pregnancy.
GSK’s commitment to respiratory disease
For 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.
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.
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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 Principal risks and uncertainties in the company’s Annual Report on Form 20-F for 2018.