GlaxoSmithKline PLC Breo Ellipta US regulatory submission (9137K)

TIDMGSK

RNS Number : 9137K

GlaxoSmithKline PLC

30 June 2014

Issued: Monday 30 June 2014, London UK & South San Francisco, CA, USA - LSE Announcement

GSK and Theravance announce submission to US regulatory authorities for fluticasone furoate/vilanterol in asthma

GlaxoSmithKline plc (LSE/NYSE: GSK) and Theravance, Inc. (NASDAQ: THRX) today announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for a fixed dose combination of the inhaled corticosteroid, fluticasone furoate and the long-acting beta(2) agonist, vilanterol (FF/VI) as a once-daily treatment for asthma in patients aged 12 years and older, with the brand name of Breo(R) Ellipta(R) .

The sNDA is seeking approval for two dose regimens, 100/25mcg and 200/25mcg, administered once daily using the Ellipta dry powder inhaler.

Today's filing is based upon data generated from the comprehensive clinical development programme for FF/VI in asthma. The clinical development programme comprised 48 clinical pharmacology studies in 1,328 subjects and 23 clinical studies in 12,051 patients with asthma, including the Phase III efficacy and safety study of FF/VI reported in December 2013.

About asthma

Asthma is a chronic lung disease that inflames and narrows the airways, causing recurring periods of wheezing, chest tightness, shortness of breath and coughing which often occurs at night or early in the morning.(1)

Despite medical advances, more than half of patients continue to experience poor control and significant symptoms.(2)

The causes of asthma are not completely understood but likely involve an interaction between a person's genetic make-up and the environment. Key risk factors are inhaled substances that provoke allergic reactions or irritate the airways. These include allergens such as dust mites and pets.(1)

About Breo Ellipta in the US

FF/VI 100/25mcg was approved by the US Food and Drug Administration under the brand name Breo Ellipta in May 2013 as a prescription medication for the long-term, once-daily, maintenance treatment of airflow obstruction and for reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Breo Ellipta is not indicated for the relief of acute bronchospasm or the treatment of asthma in the US.

Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta.

Important Safety Information (ISI) for Breo Ellipta (FF/VI) in COPD in the US

The following ISI is based on the Highlights section of the U.S. Prescribing Information for Breo Ellipta (fluticasone furoate 100 mcg / vilanterol 25 mcg) for the maintenance treatment of airflow obstruction in patients with COPD and to reduce exacerbations of COPD in patients with a history of exacerbations. Please consult the full Prescribing Information for all the labeled safety information for Breo Ellipta.

Long-acting beta(2) -adrenergic agonists (LABAs), such as vilanterol, one of the active ingredients in Breo Ellipta, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of all LABAs, including vilanterol. In the US, the safety and efficacy of Breo Ellipta in patients with asthma have not been established and therefore Breo Ellipta is not indicated for the treatment of asthma.

Breo Ellipta is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients.

Breo Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta(2) -agonist.

Breo Ellipta should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result.

Oropharyngeal candidiasis has occurred in patients treated with Breo Ellipta. Patients should rinse their mouth with water without swallowing after inhalation to help reduce this risk.

An increase in the incidence of pneumonia has been observed in subjects with COPD receiving the fluticasone furoate/vilanterol combination, including Breo Ellipta100 mcg/25 mcg, in clinical trials. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal.

Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients.

Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals.

Caution should be exercised when considering the co-administration of Breo Ellipta with long--term ketoconazole and other known strong CYP3A4 inhibitors because increased systemic corticosteroid and cardiovascular adverse effects may occur.

As with other inhaled medicines, Breo Ellipta can produce paradoxical bronchospasm which may be life-threatening. Vilanterol, the LABA in Breo Ellipta, can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias. Decreases in bone mineral density have been observed with long-term administration of products containing inhaled corticosteroids, as have glaucoma, increased intraocular pressure, and cataracts.

Breo Ellipta should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients. Beta-adrenergic agonist medicines may produce transient hyperglycemia in some patients.

The most common adverse reactions (>=3% and more common than in placebo) reported in two 6-month clinical trials with Breo Ellipta (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%). In addition to the events reported in the 6-month studies, adverse reactions occurring in >=3% of the subjects treated with Breo Ellipta in two 1-year studies included COPD, back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, influenza, pharyngitis, diarrhea, peripheral edema, and pyrexia.

RELVAR(R) , BREO(R) , and ELLIPTA(R) are trade marks of the GlaxoSmithKline group of companies.

V A Whyte

Company Secretary

30 June 2014

GSK - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

Theravance, Inc., A Royalty Management Company - is focused on maximizing the potential value of the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR(R) /BREO(R) ELLIPTA(R) and ANORO(TM) ELLIPTA(R) , with the intention of providing capital returns to stockholders. Under the Long-Acting Beta(2) Agonist (LABA) Collaboration Agreement with GSK, Theravance is eligible to receive the associated royalty revenues from RELVAR(R)/BREO(R) ELLIPTA(R) (fluticasone furoate/vilanterol, "FF/VI"), ANORO(TM) ELLIPTA(R) (umeclidinium bromide/vilanterol, "UMEC/VI") and if approved and commercialized, VI monotherapy. Theravance is also entitled to a 15% economic interest in any future payments made by GSK relating to the combination of UMEC/VI/FF and the Bifunctional Muscarinic Antagonist-Beta(2) Agonist (MABA) program, as monotherapy and in combination with other therapeutically active components, such as an inhaled corticosteroid, and any other product or combination of products that may be discovered and developed in the future under its LABA Collaboration Agreement with GSK (other than RELVAR(R) /BREO(R) ELLIPTA(R) , ANORO(TM) ELLIPTA(R) and VI monotherapy). For more information, please visit Theravance's web site at www.thrxinc.com.

References

(1.) Global Initiative for Asthma. Pocket Guide for asthma management and prevention. Updated 2014.

(2.) Demoly et al. Eur Respir Rev. 2012 Mar 1;21(123):66-74. doi: 10.1183/09059180.00008111.

 
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