ERS 2012: studies show Novartis’s dual bronchodilator beats the competition.
ERS 2012: studies show Novartis's dual bronchodilator beats the competition
At the 2012 annual meeting of the European Respiratory Society in Vienna, Austria, Novartis presented considerable data for its candidate QVA149 (a combination of indacaterol and glycopyrrolate) in chronic obstructive pulmonary disease. The data add to mounting evidence of the potential for this dual bronchodilator to provide an improved treatment option for patients.
Overall, 14 abstracts were presented by Novartis, including data from three studies in the long-acting beta 2 agonist/long-acting anticholinergic (LABA/LAMA) combination’s Phase III IGNITE program: SHINE, ILLUMINATE, and ENLIGHTEN. Together, these studies help to position the candidate as an innovative treatment option which can help to simplify treatment for chronic obstructive pulmonary disease (COPD) patients often requiring two or more inhalers.
In the SHINE study, QVA149 (110/50mcg) met its primary endpoint demonstrating improved lung function compared to indacaterol (150mcg) monotherapy (+70mL, p<0.001) and glycopyrronium (50mcg) monotherapy (+90, p<0.001). This result shows a clear benefit of combining the two bronchodilators. For patients requiring more than one bronchodilator, the combination therefore offers the advantage of simplified treatment. The trial furthermore showed that QVA149 had a greater positive effect on lung function compared to open-label tiotropium (18mcg, +80mL, p<0.001) and placebo (+200mL, p<0.001). QVA149 also performed well against a number of other measures including health-related quality of life, as measured by the St. George’s Respiratory Questionnaire (p<0.01 versus placebo; p<0.05 versus open label tiotropium).
In the ILLUMINATE study, meanwhile, QVA149 (110/50mcg) was compared head-to-head to twice-daily salmeterol/fluticasone (50/500mcg) over 26 weeks. Mean forced expiratory volume in one second (FEV1) area under the curve at week 26 was significantly higher with QVA149, such that the study met its primary endpoint (+140mL, p<0.001). QVA149 also performed better at day one and week 12, and significantly reduced breathlessness and rescue medication use. Results from this study are highly encouraging for Novartis as salmeterol/fluticasone (Advair) is currently the most popular combination product for COPD, with Datamonitor estimating 2012 COPD sales for the brand of $2.3bn across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK).
QVA149 was compared to placebo in the ENLIGHTEN study. The combination showed improved lung function at day one and week 52, and at numerous points during the study. At week 52, the mean difference in FEV1 versus placebo at 60 minutes post-dose was +256mL (p<0.001). In each of these three studies QVA149 was well tolerated with a similar incidence of adverse events across treatment groups.
These positive data for the combination add to a considerable pool of data already available for its indacaterol component. Novartis’s indacaterol became available as the first once-daily LABA in December 2009 in the EU in both 150mcg and 300mcg doses, branded as Onbrez Breezhaler. In the US, where it is branded as Arcapta Neohaler, indacaterol was approved in a 75mcg dose in July 2011. Also in July 2011, Onbrez Inhalation Capsules (150mcg) gained approval in Japan.
Indacaterol and QVA149 are part of Novartis’s COPD portfolio, which contains a number of products each being developed in the Breezhaler device. The company notes that the device allows patients to hear, feel, and see that they have taken the drug correctly. With many patients choosing their preferred treatment on the basis of the inhaler device, Novartis will benefit from focusing on the development of an easy to use inhaler, and its current availability with indacaterol will allow patients and physicians to gain experience prior to QVA149’s launch.
These new trial results help to position QVA149 against currently available therapies, particularly with QVA149 performing well against the most commonly prescribed monotherapy and combination brands in COPD, Spiriva (tiotropium) and Advair (salmeterol/fluticasone). More broadly, the trials help to cement the view that a LABA/LAMA combination will provide a significant new treatment option for patients with COPD.
Datamonitor expects QVA149 to be the first LABA/LAMA combination to launch in the EU and Japan, with forecast launch dates of Q2 2014 and Q4 2014 respectively, and anticipated sales of around $300m by 2020.
In the US, the fact that indacaterol was only approved at a lower dose delayed development of the combination for that market, and led to uncertainty over its potential. However, Novartis now states that US filing of the combination is expected at the end of 2014. With QVA149 delivering positive results across its Phase III program, Datamonitor expects that anticipation for the combination in the US will continue to grow. With development progressing in the US, Novartis will be able to maximize the return on its innovative COPD portfolio.