Date: 2015-04-30
Type of information: Refusal of a Market Authorisation in the US
Product name: Breo® Ellipta®/Relvar™ Ellipta™ (previously referred to as Relovair®)
Compound: fluticasone furoate and vilanterol
Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases
Action mechanism: corticosteroid. long-acting beta2-agonist (LABA). Breo Ellipta® works by decreasing inflammation in the lungs and helping the muscles around the airways of the lungs stay relaxed to increase airflow and reduce exacerbations in patients with COPD. Relvar® is a combination of the inhaled corticosteroid, fluticasone furoate, and the long-acting beta2-agonist (LABA), vilanterol.
Company: GSK (UK) Theravance (USA - CA)
Disease: asthma in 12-17 year old children
Latest news: * On April 30, 2015, GSK and Theravance announced that the FDA issued a complete response letter related to the proposed use of Breo Ellipta® in patients aged 12-17 stating that the data submitted do not show adequate risk-benefit to support the approval in these patients. The FDA stated that additional data would be required to further demonstrate the safety and efficacy in this population. The efficacy and safety of Breo Ellipta was studied in a clinical trial programme involving over 12,000 subjects in 23 studies of patients aged 12 and over. * On March 19, 2015, GSK and Theravance announced the outcome of the joint meeting of the Pulmonary-Allergy Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee of the FDA regarding the supplemental New Drug Application (sNDA) for Breo® Ellipta® (fluticasone furoate/vilanterol [FF/VI]) as a once-daily inhaled treatment for asthma in patients aged 12 years and older. The FDA Advisory Committee voted that the efficacy and safety data for FF/VI 100/25 mcg and 200/25 mcg once daily in asthma support approval in adults 18 years of age and older (16 for, 4 against). The Committee voted that the efficacy data provides substantial evidence of a clinically meaningful benefit in adults (18 for, 2 against) and that the safety in this population has been adequately demonstrated (17 for, 3 against). The Committee voted against approval for the proposed indication in 12-17 year olds (2 for, 18 against)*. The Committee voted that the efficacy data was not sufficient to demonstrate the benefit (4 for, 16 against) and the safety (1 for, 19 against) has not been adequately demonstrated in this sub-population. The Committee recommended that a large LABA safety trial with FF/VI should be required in adults (13 yes, 7 no) and in 12-17 year olds (17 yes, 2 no and 1 no-vote), similar to the ongoing LABA safety trials being conducted as an FDA Post-Marketing Requirement by each of the manufacturers of LABA containing asthma treatments. FDA Advisory Committees provide non-binding recommendations for consideration by the FDA . Based on these opinions and the data presented, the FDA will make its final decision on approval, which is expected on 30 April 2015 (the Prescription Drug User Fee Act goal date). *On June 30, 2014, GSK and Theravance have announced the submission of a supplemental New Drug Application (sNDA) to the FDA for a fixed dose combination of the inhaled corticosteroid, fluticasone furoate and the long-acting beta2 agonist, vilanterol (FF/VI) as a once-daily treatment for asthma in patients aged 12 years and older, with the brand name of Breo® Ellipta®. The sNDA is seeking approval for two dose regimens, 100/25mcg and 200/25mcg, administered once daily using the Ellipta dry powder inhaler. The 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 . * On November 18, 2013, GSK and Theravance have announced that the European Commission has granted marketing authorisation for Relvar® Ellipta®, which is now licensed across 31 European countries for the following uses: Asthma: the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate: patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short-acting beta2-agonists COPD: the symptomatic treatment of adults with chronic obstructive pulmonary disease (COPD) with a FEV1 < 70% predicted normal (post-bronchodilator) with an exacerbation history despite regular bronchodilator therapy. Two strengths have been licensed for the treatment of asthma (92/22 mcg and 184/22 mcg) and one strength has been licensed for the treatment of COPD (92/22 mcg). Both strengths will be administered once-daily using Ellipta, a new dry powder inhaler (DPI). Under the terms of the 2002 LABA collaboration agreement, Theravance is obligated to make a milestone payment to GSK of $15 million following marketing authorisation for Relvar® Ellipta® from the European Commission . A further $15 million payment to GSK will follow the launch of Relvar®Ellipta® in Europe . As part of its assessment, the European Medicines Agency reviewed results of 10 clinical studies in 7,783 patients with COPD and 16 studies in 9,326 patients with asthma. * On September 20, 2013, GSK and Theravance have announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing authorisation for fluticasone furoate/vilanterol (FF/VI) under the proposed brand name Relvar™ Ellipta™ for the treatment of asthma and chronic obstructive pulmonary disease. Two strengths of FF/VI are proposed for asthma (92/22 mcg and 184/22 mcg) and one strength is proposed for COPD (92/22 mcg). All strengths will be administered once-daily using the Ellipta, a new dry powder inhaler (DPI). A final decision by the European Commission is anticipated during the fourth quarter of 2013. As part of its assessment, the EMA reviewed results of 11 clinical studies in 7,851 patients with COPD and 16 studies in 9,326 patients with asthma. FF/VI 100/25 mcg was approved by the FDA in May 2013 under the trade name Breo Ellipta®. It was also approved for the treatment of COPD by Health Canada in July 2013 under the same trade name. * On July 13, 2012, GSK and Theravance have announced the submission of regulatory applications in the US and European Union for the once-daily investigational medicine fluticasone furoate /vilanterol for patients with chronic obstructive pulmonary disease. GSK and Theravance have completed their phase 3 registration programme in January. - In Europe, the Marketing Authorisation Application (MAA), with the proposed brand name Relvar®, administered by a new dry powder inhaler called Ellipta®, has been submitted to the EMA for the following indications: COPD (100/25mcg): The symptomatic treatment of patients with COPD with a FEV1 < 70% predicted normal (post-bronchodilator) in patients with an exacerbation history. - In the US, the New Drug Application (NDA), with the proposed brand name Breo™, administered by the Ellipta™ inhaler, has been submitted to the FDA, for the following indication: COPD (100/25mcg): The long-term once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema and to reduce exacerbations of COPD in patients with a history of exacerbations.
Patents:
Submission of marketing authorization application USA : 2014-06-30
Submission of marketing authorization application UE: 2012-07-13
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2013-11-18 (asthma and COPD)
Favourable opinion UE: 2013-09-19
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
