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New Drugs Online Report for fluticasone furoate + vilanterol trifenatate
Information
Generic Name:
fluticasone furoate + vilanterol trifenatate 
Trade Name: Relvar Ellipta (EU), Breo (US) 
Synonym: 642444, 444, Relovair 
Entry Type: Licence extension  
 
Developmental Status
UK: Launched 
EU: Launched 
US: Pre-registration (Filed) 
UK launch Plans: Available only to registered users
Actual UK launch date: 01/01/2014 
Comments
Jun 14: GSK & Theravance file a supplemental New Drug Application with the FDA for Breo Ellipta as a treatment for asthma in patients aged 12 years and over [14]. 
01/07/2014 13:33:37
Jan 14: Launched in the UK for treating asthma & COPD. Price: one inhaler x 30 doses of 92g/22g, 27.80 & 1 inhaler x 30 doses of 184g/22g, 38.87 [12]. 
10/01/2014 16:57:20
Nov 13: Approved in the EU to treat asthma & COPD [10]. 
18/11/2013 21:01:20
Sep 13: EU positive opinion for Relvar Ellipta to treat asthma & COPD. As part of its assessment, the CHMP reviewed results of 11 clinical studies in 7,851 patients with COPD and 16 trials in 9,326 asthma patients with asthma. A final decision by the European Commission is expected during the fourth quarter [9]. 
20/09/2013 15:13:03
Jul 12: Filed in the EU for the regular treatment of asthma in adults and adolescents aged 12 years and older, where use of a combination product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate. It is administered by a new dry powder inhaler called Ellipta [6]. 
13/07/2012 19:37:21
Jan 12: Plan to file in EU mid-2012 and will continue discussions with the FDA on the regulatory requirements for a US asthma indication [4]. 
09/01/2012 21:12:56
 
Trial or other data
Mar 14: PIII trial published in Thorax. In this study (n=2019), vilanterol plus fluticasone furoate reduced the risk of having a severe asthma exacerbation from 15.9% to 12.8% at 52 weeks, when compared to fluticasone monotherapy, in patients aged ≥12 years with uncontrolled asthma [13]. 
11/03/2014 08:41:30
Dec 13: Results from a PIII study designed to support a potential filing for asthma for adults in the US reported. For the pre-specified primary endpoint of 0-24 hour weighted mean FEV1, FF/VI 100/25mcg demonstrated a statistically significant improvement in lung function vs FF 100mcg (108ml, 95% CI 45, 171 p < 0.001) at the end of the 12 week treatment period. In patients receiving FF/VI 200/25mcg an additional improvement of 24ml (95% CI -37, 86) was observed vs FF/VI 100/25mcg [11]. 
07/12/2013 22:15:44
Feb 13: PIII (NCT01018186) study published early online in Thorax. 503 pts (aged 12 years or over) were randomised to double-blind (double-dummy) treatment with 100mcg FF/25mcg VI once daily in the evening (n=201), 200mcg FF/25mcg VI (n=202) once daily in the evening, or fluticasone propionate (FP) 500mcg twice daily (n=100). Three pts (1%) on FF/VI 100/25mcg, six (3%) on FF/VI 200/25mcg and three (3%) on FP experienced a severe exacerbation during the treatment period. Three pts (one on FF/VI 100/25mcgg and two on FP) were hospitalised as a result (none required intubation). On-treatment AEs (FF/VI 6669%; 73% FP) and the number of withdrawals due to an AE were similar across treatment groups. Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (67%) than FP (3%). Twelve serious AEs were reported; one of which (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52. No clinically important changes in non-fasting glucose, potassium, QT interval or ophthalmic assessments were reported [8]. 
26/02/2013 08:40:23
Sep 12: NCT01686633 is a PIII randomized, double-blind multicentre study of fluticasone furoate/vilanterol 200/25mcg or 100/25 mcg inhalation powder, and fluticasone furoate 100mcg inhalation powder in the treatment of persistent asthma in 990 adults and adolescents. The primary outcome is weighted mean serial FEV1 at week 12. The study will start Sep 12 and is due to complete Oct 13 [7]. 
19/09/2012 11:11:04
Mar 12: The PIII registrational programme has been completed. The final study evaluated the efficacy and safety of FF/VI and FP vs placebo in the treatment of persistent asthma in 330 adults and adolescents. Both FF and FP met the primary endpoint of a statistically significant change from baseline in trough evening FEV1 at the end of the 24-week treatment period vs placebo (p=0.009 and p=0.011, respectively). The most common AEs on the FF arm were bronchitis, headache, nasopharyngitis, upper RTI, pharyngitis and sinusitis [5]. 
26/03/2012 15:55:22
Jan 12: All but one PIII registration studies now complete. An exacerbation study, which randomized around 2,000 patients for up to 76 weeks, found FF/VI 100/25mcg significantly increased time to first severe exacerbation (p=0.036) and significantly decreased annual rate of severe exacerbations (p=0.014) vs to fluticasone alone (FF). FF/VI improved trough FEV1 at all pre-defined time points over the 76-week treatment period (p<0.001 vs. FF). The most frequent AEs were headache, nasopharyngitis, upper respiratory tract infection, bronchitis, cough, oropharyngeal pain and influenza. There were no differences in the number of asthma-related hospitalisations between treatment arms. There were no asthma-related deaths. A 24-week study in around 600 patients with moderate to severe asthma demonstrated FF/VI 200/25mcg was superior vs FF 200mcg on both trough FEV1 (p < 0.001) and weighted mean FEV1 (p=0.048). FF 200mcg dosed once daily was non-inferior to fluticasone propionate (FP) 500mcg dosed twice daily on trough FEV1. In a 12-week placebo-controlled study evaluating lung function in around 600 patients with mild to moderate asthma, FF/VI 100/25mcg did not demonstrate statistically significant improvements vs FF 100mcg on either trough FEV1 (p=0.405) or weighted mean FEV1 (p=0.06). Both FF/VI and FF demonstrated statistically significant improvements against placebo on the same endpoints (p<0.001). In a 12-week study conducted in around 340 patients receiving inhaled corticosteroids, once-daily VI 25mcg and twice-daily salmeterol (SAL) 50mcg showed no statistically significant difference on 24-hour weighted mean FEV1 vs placebo. The lack of numerical improvement of SAL over placebo was unexpected and confounded interpretation of the study. In a non-pivotal 24-week superiority study FF/VI 100/25mcg once daily did not meet the predefined threshold for superiority on 0-24 hour weighted mean FEV1 (p=0.162) vs Seretide [4].  
09/01/2012 21:12:43
Aug 10: GSK is to license Vectura´s dry powder drug formulation patents for GSK642444 [3] 
06/08/2010 22:34:58
Jul 10: NCT01165138 (HZA106827) is a randomised, double-blind, placebo-controlled (with rescue medication), parallel group multicentre study of fluticasone furoate/ vilanterol vs fluticasone furoate alone in the treatment of persistent asthma in 1,000 adults and adolescents. The primary outcomes, at the end of the 12 week treatment period, are change in clinic visit trough (pre-bronchodilator and pre-dose) FEV1 in all subjects and weighted mean serial FEV1 over 0-24 hours post-dose in a subset. The study is due to start Aug 10 and complete Aug 11 [2]. 
19/07/2010 16:47:11
Mar 10: First pt enrolled in the PIII randomised, double-blind, parallel-group, 24 week asthma exacerbation study with Relovair (fluticasone furoate/vilanterol trifenatate) (worldwide study). Study will assess Relovair (100/25mcg) against fluticasone furoate (100mcg) in pts with uncontrolled asthma despite current treatment. Main outcome = time to first severe asthma exacerbation. The ongoing 12 month safety study will assess the overall safety profile of Relovair and has been designed to support both the asthma and COPD indications. (1) 
23/03/2010 09:22:08
Mar 10: Patients across all of the Relovair programmes will be dosed using a unique single step activation inhaler. (1) 
23/03/2010 09:20:49
Mar 10: Asthma programme (consisting of 8 studies) will evaluate potential benefit of Relovair vs. component products and existing asthma treatments. Six efficacy studies, including 3 comparator studies, are schedule to start in the next quarter: (1) a 24 week head to head study of Relovair vs. Advair/Seretide, (2) a 24 week fluticasone furoate vs. fluticasone propionate vs. placebo study, (3) a 12 week vilanterol trifenatate vs. salmeterol vs. placebo study, (4) a 12 week low dose combination study, (5) 24 week higher dose combination study vs. components and an HPA axis study and (6) 24 wk head to head study of Relovair vs. fluticasone. (1) 
23/03/2010 09:20:01
 
Evidence Based Evaluations
AWMSG  http://www.awmsg.org/awmsgonline/app/appraisalinfo/1216 
SMC  http://www.scottishmedicines.org.uk/SMC_Advice/Advice/966_14_fluticasone_furoate_vilanterol_Relvar/fluticasone_furoate_vilanterol_Relvar_Ellipta 
NICE (MPC)  http://publications.nice.org.uk/esnm34-asthma-fluticasone-furoatevilanterol-relvar-ellipta-combination-inhaler-esnm34/key-points-from-the-evidence 
EPAR  http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002673/human_med_001708.jsp&mid=WC0b01ac058001d124 
   
References  
Available only to registered users
Category
BNF Category:
Corticosteroids (03.02)
Pharmacology: Long-acting beta agonist (LABA) in combination with the once-a-day inhaled corticosteroid (ICS), fluticasone furoate (FF)  
Epidemiology: At least 1 in 10 children and 1 in 20 adults have asthma.  
Indication: Asthma 
Additional Details: in adults and adolescents aged 12 years and older  
 
Method(s) of Administration
Inhalation 
 
Company Information
Name: GlaxoSmithKline 
US Name: GlaxoSmithKline 
 
NICE Information
In timetable: No  
When:  /