From GSK:

GSK receives approval for Encruse® Ellipta® in Japan for the treatment of COPD

26 March 2015

Issued: London

-      Two further GSK products, Duac® Combination Gel and Synflorix™, also gain approval in Japan

GlaxoSmithKline plc (LSE/NYSE: GSK) announced today that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Encruse® Ellipta® (umeclidinium) for the relief of various symptoms due to airway obstruction with chronic obstructive pulmonary diseases (chronic bronchitis, pulmonary emphysema) (COPD).

Encruse is a once-daily long-acting muscarinic antagonist (LAMA), a type of bronchodilator that can improve airflow in and out of the lungs. Encruse is a 62.5mcg strength inhalation powder delivered in the Ellipta inhaler.

Darrell Baker, SVP & Head, GSK Global Respiratory Franchise, said, “We are proud of this approval for Encruse Ellipta as it means healthcare professionals in Japan will have another treatment option for appropriate COPD patients. Encruse is our first LAMA monotherapy and the second treatment from our new COPD portfolio to be approved in Japan within the last year. The Ellipta inhaler has been positively received by physicians in Japan and today’s approval reflects our goal of providing a range of respiratory medicines in a consistent inhaler that enables physicians to meet the specific needs of individual patients.”

Following this approval, it is expected that launch will take place in Japan in 2015.

The MHLW assessment of umeclidinium included a review of ten phase III clinical trials which included approximately 4,000 COPD patients treated with umeclidinium or placebo. Within this, 983 patients received the approved dose of umeclidinium 62.5mcg once-daily.

Approval of Duac® Combination Gel 
The MHLW also today announced the approval of Duac® Combination Gel in Japan, for use in the treatment of acne vulgaris. Duac® Combination Gel (clindamycin 1%-benzoyl peroxide 3%) is the first fixed-dose combination topical treatment for acne in Japan.

Approval of Synflorix
Synflorix™, a pneumococcal conjugate paediatric vaccine, was also approved today by the MHLW, with an indication for the prevention of invasive infectious diseases and pneumonia caused by pneumococcus (serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). Synflorix™ was developed by GSK and is commercialised by Japan Vaccine Co., Ltd., a joint venture between GSK and Daiichi Sankyo Co., Ltd.

Japanese Drug Information for these products will be available soon at http://glaxosmithkline.co.jp/healthcare/. Prior to the label being posted online, a copy of the label may be requested from one of the GSK Media or Investor Relations contacts listed in the “GlaxoSmithKline enquiries” section at the end of this document.

About COPD
COPD is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing. COPD is thought to affect approximately 8.6% of the population aged over 40 in Japan.

Long-term exposure to lung irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke, breathing in second hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD. Most people who have COPD are at least 40 years old when symptoms begin.

Important Safety Information for Encruse Ellipta (umeclidinium) 
The following Important Safety Information (ISI) is based on a summary of the Japanese Drug Information for Encruse Ellipta. Please consult the full Drug Information for all the labeled safety information for Encruse Ellipta.

Encruse Ellipta is contraindicated in patients with narrow-angle glaucoma, impaired urination or a hypersensitivity to umeclidinium, or any of the excipients.

Encruse Ellipta should be administered with care in patients with current or past history of cardiac failure, atrial fibrillation or extrasystoles and in patients with prostatic hyperplasia.

Encruse Ellipta is not indicated for the acute treatment of COPD exacerbations. In order to stabilize symptoms of COPD, continuous use of Encruse Ellipta is essential. However, if a patient does not respond to Encruse Ellipta taken with the correct dosage and administration, treatment with Encruse Ellipta is considered inappropriate for the patient and should be discontinued without hesitation.

As with other inhalation therapies, paradoxical bronchospasm that may be life-threatening may occur after inhalation of Encruse Ellipta. If paradoxical brochospasm occurs, treatment with Encruse Ellipta should be discontinued immediately and alternative therapy should be instituted.

In three global phase III clinical studies, adverse reactions including laboratory abnormalities were reported in 71 (7.4%) of a total of 963 patients (including 52 Japanese patients) treated with Encruse Ellipta or umeclidinium (UMEC) 125 μg*. The most common adverse reactions are cough reported in 6 patients (0.6%), dyspnoea in 3 patients (0.3%), oropharyngeal pain in 3 patients (0.3%), constipation in 3 patients (0.3%), dysgeusia in 3 patients (0.3%), and upper respiratory tract infection in 3 patients (0.3%).

Atrial fibrillation may occur. If any abnormality is observed, treatment should be discontinued and appropriate measures should be taken.

Other adverse events include tachycardia, cough, dry mouth and constipation which were reported in <1% of patients.

In a Japanese 52 week long-term administration study, adverse reactions including laboratory abnormalities were reported in 13 (10%) of a total of 131 patients treated with UMEC 125 μg*. The most common adverse reaction was dysphonia reported in 3 patients (2%).

*The approved dose of Encruse Ellipta in Japan is umeclidinium 62.5mcg once daily.

Other Umeclidinium Regulatory Activity:
Umeclidinium 62.5mcg has been approved in a number of countries including Canada, the European Union, and the United States. Regulatory applications for umeclidinium have been submitted and are undergoing assessment in several other countries.

Important Safety Information for Duac® Combination Gel (clindamycin 1% and benzoyl peroxide 3%)
This new fixed-dose combination Duac contains two medicines: clindamycin 1% and benzoyl peroxide 3% in a gel base formulation. This approval allows Japan to make the product available for the topical treatment of acne vulgaris. Efficacy and safety have not been established in children under 12 years of age.

The product is contraindicated in patients who have demonstrated hypersensitivity to any of the ingredients or lyncomycin antibiotics.

Contact with the mouth, eyes, lips, and other mucuous membranes or areas of irritated or broken skin should be avoided. Application to sensitive areas of skin should be made with caution. In case of accidental contact, rinse well with water. The product should not be orally ingested, in case of accidental ingestion, gastrointestinal adverse drug reactions similar to those seen with systemically administered clindamycin may occur. If such adverse drug reactions occur, physicians should symptomatically treat and monitor the patient with caution.

The product should be used with caution patients with atopic diathesis, in whom severe immediate allergy may occur and in patients with, or with a history of, regional enteritis, ulcerative colitis, or antibiotic-associated colitis (including pseudomembranous colitis).

During treatment, benzoyl peroxide-containing products can cause peeling and reddening in patients. Depending on the severity of these side effects, patients can use a non-comedogenic moisturiser, or temporarily delay dosing (skip dose); however, efficacy has not been established for less than once-daily dosing frequencies.

Patients should be advised that applying too much Duac 3% Gel or applying more than once-daily is not expected to improve efficacy, but may increase the risk of skin irritation.

If severe local irritancy (e.g. severe erythema, severe dryness and itching, severe stinging/burning) occurs, treatment should be discontinued.

As benzoyl peroxide may cause increased sensitivity to sunlight, sunlamps should not be used and deliberate or prolonged exposure to sunlight should be avoided or minimised. When exposure to strong sunlight cannot be avoided, patients should be advised to use a sunscreen product and wear protective clothing.

If a patient has sunburn, this should be resolved before using the product.

Duac 3% Gel should be administered with care when coadministered with the following drugs: erythromycin-containing products, peripherally-acting muscle relaxants, topical sulfonamide-containing products.

If prolonged or significant diarrhoea occurs or the patient suffers from abdominal cramps, treatment should be discontinued immediately, as the symptoms may indicate antibiotic-associated colitis. The product may bleach hair and coloured or dyed fabrics. Avoid contact with hair, fabrics, furniture or carpeting.

Cross resistance between clindamycin and macrolide antibacterial drugs including erythromycin has been reported. Resistance induced by erythromycin is often associated with resistance to clindamycin.

Important safety information for Synflorix™
Most common adverse reactions include pain at the injection site, redness, swelling, drowsiness, appetite loss, irritability and fever, mostly mild to moderate in severity and not long-lasting.

Synflorix™ must not be used in children hypersensitive to the active substances or any other ingredients contained in the vaccine.

In children with an acute severe febrile illness, vaccination should be postponed; presence of a mild infection, such as a cold, should not result in the deferral of vaccination.

Synflorix™ should be given with caution to individuals with thrombocytopenia or any coagulation disorder.

Encruse Ellipta is known by the brand name Incruse Ellipta in markets outside of Japan.

Encruse®, Incruse®, Ellipta®, SynflorixTM and Duac® are trade marks of the GSK group of companies.

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.