Home | Clinical | New Drugs Online
NDO Logo

Home | Additional information is available to accredited, [registered, NHS users]

New Drugs Online Report for indacaterol + glycopyrronium bromide
Information
Generic Name:
indacaterol + glycopyrronium bromide 
Trade Name: Ultibro/Ulunar/Xoterna (EU) 
Synonym: QVA149A 
Entry Type: New formulation  
 
Developmental Status
UK: Approved (Licensed) 
EU: Launched 
US: Phase III Clinical Trials 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Apr 14: Launched in Denmark and Ireland in Jan 14 [30] 
16/04/2014 16:45:41
Feb 14: Indacaterol 85 mcg/glycopyrronium 43 mcg will be marketed as Ultibro in the UK by Novartis; Xoterna and Ulunar are alternative brand names that will be used in other EU countries [29]. 
28/02/2014 11:30:43
Feb 14: EU positive opinion recommending the granting of a marketing authorisation for Ulunar Breezhaler, 85 mcg/43 mcg, inhalation powder, hard capsule intended for maintenance bronchodilator treatment to relieve symptoms in adults with COPD [28]. 
24/02/2014 11:37:40
Sept 13: European Commission approved once-daily Ultibro® Breezhaler® (indacaterol 85 mcg / glycopyrronium 43 mcg) as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). [27] 
24/09/2013 10:07:07
Jul 13: EU positive opinion for Ultibro/Xoterna Breezhaler to be used as a maintenance bronchodilator treatment to relieve symptoms in adults with COPD [26]. 
26/07/2013 14:14:24
Oct 12: Filed in the EU for approval of a fixed dose combination inhaler of indacaterol maleate 110micrograms/glycopyrronium bromide 50 micrograms [20].  
26/10/2012 10:50:10
Aug 12: Plans to file in EU and Japan Q4 2012. US filing is expected at the end of 2014 because of delays associated with dosage concerns [17]. 
31/08/2012 09:24:33
Oct 11: In the US, glycopyrrolate will require additional clinical data to support filing and will consequently be delayed. The changes to the US glycopyrrolate program will similarly impact approval timing for QVA149 in the US, where additional clinical studies will be required. The QVA149 submission remains on track for 2012 in EU [8]. 
25/10/2011 20:02:29
Filings planned 2012 (4) 
11/06/2010 12:45:58
MDI combination inhaler (1) 
13/04/2010 12:37:29
 
Trial or other data
Sept 14: Data from LANTERN study (n=744) presented at European Respiratory Society Congress. Ultibro was superior to Seretide accuhaler in reducing exacerbations and improving lung function. Rate of moderate-to-severe exacerbations was reduced with Ultibro by 31% vs. Seretide. [32] 
08/09/2014 10:34:23
May 14: Novartis announces positive data from the QUANTIFY study, which met its primary endpoint of showing non-inferiority of Ultibro Breezhaler compared to tiotropium 18mcg once daily/formoterol 12mcg twice daily in improving health-related quality of life outcomes. Ultibro Breezhaler induced superior improvements in lung function at 26 weeks vs. tiotropium plus formoterol, & patients taking Ultibro were more likely to demonstrate a clinically meaningful improvement in shortness of breath and health-related quality of life [31]. 
22/05/2014 12:21:08
Jun 13: PIII SHINE published in Eur Resp J [25]. 
19/06/2013 09:02:30
May 13: ILLUMINATE published in the Lancet [24]. 
08/05/2013 08:27:54
Apr 13: Results from the 64-week SPARK study published in Lancet Respiratory Medicine (doi:10.1016/S2213-2600(13)70052-3). The study met its primary endpoint: QVA149 significantly reduced the rate of moderate or severe COPD exacerbations by 12% vs glycopyrronium (p=0.038) (but not vs tiotropium 18mcg (p=0.096)). The rate of all (mild, moderate, and severe) exacerbations was reduced by 15% with QVA149 vs glycopyrronium (p=0.0012) and by 14% vs tiotropium (p=0.0017). Lung function (trough FEV1) was significantly higher with QVA149 vs glycopyrronium (p<0.0001) and tiotropium (p<0.0001) at each assessment during the treatment period. Percentages of patients achieving the minimum clinically important (≥4 unit) improvement in SGRQ total scores were higher with QVA149 vs glycopyrronium (p=0.055) or tiotropium (p=0.051), even up to Week 64 There was no meaningful difference between the treatment groups in the incidence of adverse and serious adverse event reporting [23]. 
24/04/2013 09:22:42
Apr 13: NCT01834885 is a PIII multi-centre, randomized, double-blind, double-dummy study to of QVA149 vs fluticasone/salmeterol in 554 COPD patients with moderate to severe airflow limitation. The primary outcome is AUC 0-12 hours for FEV1 following 12 weeks of treatment. The study starts Apr 13 and is due to complete Dec 13 [22]. 
19/04/2013 10:06:25
Nov 12: NCT01727141 is a 12-week treatment, multi-centre, randomized, double-blind placebo and active controlled study to assess the efficacy, safety, and tolerability of indacaterol maleate / glycopyrronium bromide in 1,000 COPD patients with moderate to severe airflow limitation. The primary outcome is FEV1 at 12 weeks. Inclusion criteria include patients with a post-bronchodilator FEV1 of ≥30% and < 80% predicted and a post-bronchodilator FEV1/FVC <0.7. The study will start Dec 12 and is due to complete Jan14 [21] 
22/11/2012 11:06:20
Sep 12: NCT01682863 a PIII multi-centre randomized double blind 52-week study to assess the safety of QVA149 vs indacterol in 400 patients with COPD who have moderate to severe airflow limitation. The study starts Oct 12 and is due to complete Jun 14 [19] 
19/09/2012 13:30:54
Sep 12: Further data from ENLIGHTEN reported at the European Respiratory Society Congress. In ENLIGHTEN, QVA149 increased FEV1 and forced vital capacity (FVC) vs placebo at Day 1 and Weeks 3, 6, 12, 26, 39 and 52 (p<0.001). At Week 52, the mean difference in FEV1 vs placebo at 60 minutes post-dose was +257mL (p<0.001) [18]. 
05/09/2012 08:44:46
Sep 12: Further data from ILLUMINATE reported at the European Respiratory Society Congress. ILLUMINATE compared QVA149 110/50mcg to twice-daily LABA/ICS salmeterol/fluticasone 50/500 mcg head-to-head over 26 weeks in patients with COPD. The study met its primary endpoint; mean FEV1 (AUC) for 0-12hr at Week 26 was significantly higher with QVA149 (+140mL; p<0.001). Mean FEV1 AUC0-12h was also significantly higher with QVA149 at Day 1 (+70mL; p<0.001) and Week 12 (+120mL; p<0.001). QVA149 significantly improved breathlessness measured by transition dyspnea index (p=0.003) and reduced rescue medication use (p=0.019) over 26 weeks vs salmeterol/fluticasone [18]. 
05/09/2012 08:44:35
Sep 12: Further data reported on the SHINE study from the European Respiratory Society Congress. SHINE met its primary endpoint; once-daily QVA149 110/50 mcg improved lung function as measured by trough FEV1 vs once-daily indacaterol maleate 150 mcg (+70mL above indacaterol alone; p<0.001) and once-daily glycopyrronium 50 mcg (+90mL above glycopyrronium alone; p<0.001). QVA149 was also more effective than tiotropium 18 mcg (+80mL above tiotropium; p<0.001) and placebo (+200mL; p<0.001). Mean peak FEV1 at Week 26 was also significantly higher with QVA149 vs placebo (+330mL, p<0.001), indacaterol 150 mcg (+120mL; p<0.001), glycopyrronium 50 mcg (+130mL; p<0.001) and OL tiotropium 18 mcg (+130mL; p<0.001). Mean FEV1 (AUC) for 0-24hr at Week 26 was significantly higher with QVA149 vs placebo (+320mL, p<0.001), indacaterol 150 mcg (+110mL; p<0.001), glycopyrronium 50 mcg (+110mL; p<0.001) and OL tiotropium 18 mcg (+110mL; p<0.001). .QVA149 improved breathlessness measured by the transition dyspnea index (p<0.001 vs placebo; p<0.05 vs tiotropium 18 mcg), increased health-related quality of life (HRQoL) measured by the St George´s Respiratory Questionnaire or SGRQ (p<0.01 vs placebo; p<0.05 vs tiotropium 18 mcg) and reduced rescue medication use (p<0.001 vs both placebo and tiotropium 18 mcg). QVA149 was superior to indacaterol 150 mcg and glycopyrronium 50 mcg at reducing use of rescue medication (p<0.05 and p<0.001 respectively) and also provided numerically higher improvements in breathlessness and HRQoL vs indacaterol 150 mcg and glycopyrronium 50 mcg [18].  
04/09/2012 11:58:31
Aug 12: Top line results reported from the 5th and final PIII study in the IGNITE programme, SPARK. SPARK was a 64-week, multicentre, randomized, double-blind, active controlled study to assess the effect of QVA149 (indacaterol maleate 110mcg / glycopyrronium 50mcg) once daily vs glycopyrronium 50mcg and vs open label once daily tiotropium 18mcg on moderate-to-severe COPD exacerbations in 2,224 patients with severe to very severe COPD. Patients on QVA149 demonstrated a clinically meaningful and statistically significant lower rate of exacerbations vs patients treated with glycopyrronium (p=0.038). The rate of exacerbations was numerically lower (p=0.096) in patients on QVA149 vs open-label (tiotropium [17].  
31/08/2012 09:24:54
Jun 12: NCT01610037 - a placebo and active (tiotropium) controlled study to assess the long-term safety of once daily QVA149 for 52 weeks in 1,224 patients with COPD and moderate to severe airflow limitation. The study will start Sep 12 and is due to complete Jul 14 [16]. 
08/06/2012 08:31:44
Jun 12: NCT01610037 is a PIII study assessing the long-term safety of once daily QVA149 for 52 weeks vs tiotropium and placebo in 1224 patients with COPD with moderate to severe airflow limitation. The study is planned to start Jul 12 and to complete Jul 14 [15]. 
02/06/2012 19:22:23
May 12: NCT01604278 (GLOW6): a 12-week multi-centre, RCT of NVA237 + indacaterol once daily vs. indacaterol once daily in 450 patients with moderate to severe COPD. The primary outcome is 24 hours trough FEV1. The study is planned to start May 12 and complete Jan 13 [14] 
29/05/2012 13:38:32
Apr 12: The fourth ILLUMINATE study in the IGNITE programme, has met its primary endpoint. The ILLUMINATE study in more than 500 pts demonstrated that superior lung function (measured by FEV1 AUC0-12h with a p value <0.001) was achieved with once-daily QVA149 compared with twice-daily Seretide® (fluticasone 500mcg / salmeterol 50mcg) in pts with moderate to severe COPD [12]. 
25/04/2012 17:17:45
NCT01574651 (QUANTIFY): A 26-week treatment, multicentre, randomized, blinded PIII study of QVA149 (110/50 µg once daily) in 880 patients with moderate to severe COPD, using tiotropium plus formoterol as an active control. The primary outcome is change from baseline of quality of life as assessed by St George´s Respiratory Questionnaire (SGRQ-C). The study started Apr 12 and is due to complete Apr 13 [11]. 
14/04/2012 22:46:57
Mar 12: first three QVA149 PIII studies in COPD, the SHINE, BRIGHT and ENLIGHTEN studies, which are part of the IGNITE programme, met their primary endpoints. SHINE (n> 2,100 patients) met the primary endpoint by demonstrating the superiority in trough FEV1 (p<0.001) of once-daily QVA149 vs once-daily indacaterol or once-daily NVA237 in patients with moderate to severe COPD. In addition, QVA149 showed superiority in trough FEV1 (p<0.001) vs placebo and open-label tiotropium (18 mcg). In BRIGHT patients experienced significantly better exercise endurance vs placebo (p=0.006) and ENLIGHTEN demonstrated that QVA149 was well tolerated with a safety and tolerability profile similar to placebo [10].  
02/04/2012 15:28:06
Feb 12: NCT01529632 (BEACON) is a PIII study comparing once daily QVA149 vs once daily concurrent administration of its individual consituents in 184 patients with moderate to severe COPD. The primary outcome is trough FEV1 after 28 days of blinded treatment. The study will start in May 12 and is due to complete Nov 12 [9]. 
11/02/2012 19:30:41
Apr 11: NCT01315249 (ILLUMINATE) is a PIII 26-week, multi-center, randomized, double-blind, double dummy, parallel-group study comparing once daily QVA149 vs twice daily fluticasone/salmeterol in 522 patients with moderate to severe COPD. The primary outcome is FEV1area under the curve for 0-12 hours (AUC0-12h) at 26 weeks. The study started in Mar 11 and is due to complete Mar 12 [7]. 
04/04/2011 16:11:12
Feb 11: NCT01294787 this PIII double-blind randomized 3-week study (BRIGHT) will assess the effect of once-daily QVA149 (indacaterol and glycopyrronium bromide [NVA237])) on exercise endurance in 80 patients with moderate to severe COPD vs placebo with tiotropium as an active comparator [6].  
11/02/2011 18:33:49
Sep 10: NCT01202188 (GLEAM) A PIII study active comparator study of QVA149 vs indacaterol, NVA237 and tiotropium in 2138 patients with moderate to severe COPD. The primary outcome is trough FEV1 at 26 weeks. Study starts Sep 10 and is due to complete Feb 12 [5]. 
21/09/2010 09:35:16
The two trials detailed below are NCT01120691 and NCT01120717, respectively. Each began Q2 2010 and are due to complete Q1 2012.  
30/05/2010 19:03:47
May 10: PIII clinical trial programme started: two 52 week studies. First study (n=1998 with severe or very severe COPD) is a randomised, double-blind, parallel-group trial assessing superiority of QVA 149 over glycopyrronium bromide alone in the rate of exacerbations (main outcome). Secondary outcomes include time to first exacerbation together with safety and tolerability. Second study is a randomised, double-blind, parallel-group, placebo controlled trial assessing the long term safety and tolerability of QVA 149 (n= 339 with moderate to severe COPD). FEV1 (forced expiratory volume in one second) is a secondary outcome measure. In both studies, patients will be randomised to receive a once-daily dose of either the combination product or the comparator from a single dose dry powder inhaler for a 52-week period. (2)  
11/05/2010 08:27:29
 
Evidence Based Evaluations
NICE (MPC)  http://www.nice.org.uk/Advice/ESNM33 
AWMSG  http://www.awmsg.org/awmsgonline/app/appraisalinfo/1535 
LMEN  http://www.medicinesresources.nhs.uk/en/Communities/NHS/SPS-E-and-SE-England/LNDG/London-Wide-Reviews/Ultibro-Breezhaler-indacaterolglycopyrronium/ 
EPAR  http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002679/human_med_001691.jsp&mid=WC0b01ac058001d124 
NHSC  http://www.nhsc-healthhorizons.org.uk/files/downloads/1657/2101.bcc80f68.Indacaterol.pdf 
   
References  
Available only to registered users
Category
BNF Category:
Respiratory system (03)
Pharmacology: Long-acting β2-adrenoceptor agonist plus muscarinic receptor antagonist  
Epidemiology: An estimated three million people are affected by COPD in the UK. About 900,000 have been diagnosed with COPD and an estimated two million people have COPD which remains undiagnosed. The rate of COPD in the population is estimated at between 2% and 4%. The diagnosed prevalence of COPD is 1.5%. The prevalence increases with age, with an estimated prevalence of 10% in men older than 75. [13]  
Indication: Chronic obstructive pulmonary disease (COPD) 
 
Method(s) of Administration
Inhalation 
 
Company Information
Name: Novartis 
US Name: Novartis 
 
NICE Information
In timetable: -  
   
   
PBR Likely Healthcare Resource Group included.
   
Implications Available only to registered users
   

Comments