Novartis receives CHMP positive opinion for Enerzair Breezhaler (QVM149), a potential first-in-class inhaled LABA/LAMA/ICS combination for uncontrolled asthma

  • CHMP positive opinion advances efforts to provide first-in-class LABA/LAMA/ICS combination for patients whose asthma is uncontrolled with LABA/ICS standard-of-care treatment in the EU.
  • Digital companion with app and sensor that provide inhalation confirmation, medication reminders and access to objective data to better support therapeutic decisions also covered by positive opinion for Enerzair Breezhaler (QVM149; IND/GLY/MF).
  • Decision supported by robust efficacy and safety data from over 3,000 patients with asthma in Phase III IRIDIUM study, in which once-daily IND/GLY/MF demonstrated statistically significant improvements in lung function compared with once-daily IND/MF (QMF149).1
  • In secondary analyses of the Phase III IRIDIUM study, statistically significant improvements in lung function and reductions in moderate-to-severe and severe asthma exacerbation rates were observed with high-dose IND/GLY/MF compared to high-dose Sal/Flu.1

Basel, May 1, 2020 - Novartis today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Enerzair Breezhaler (QVM149; indacaterol acetate, glycopyrronium bromide and mometasone furoate [IND/GLY/MF]) as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist (LABA) and a high dose of an inhaled corticosteroid (ICS) who experienced one or more asthma exacerbations in the previous year. If approved, this will be the first once-daily LABA/long-acting muscarinic antagonist (LAMA)/ICS fixed-dose combination for these patients. The European Commission (EC) reviews the CHMP recommendation and usually delivers its final decision in approximately two months.

"This is an important development for patients with uncontrolled asthma because IND/GLY/MF has been shown to improve lung function and symptoms versus a LABA/ICS standard-of-care," said Professor Huib Kerstjens, Head, Department of Pulmonology at the University Medical Center Groningen. "In secondary analyses of the Phase III IRIDIUM study statistically significant reductions in moderate-to-severe and severe asthma exacerbation rates were observed with high-dose IND/GLY/MF compared to high-dose salmeterol xinafoate/fluticasone propionate."

IND/GLY/MF will be administered via the dose-confirming Breezhaler device, which enables once-daily inhalation using a single inhaler. If approved, IND/GLY/MF will be the first asthma treatment in the EU that can be prescribed together with a digital companion; a Propeller Health sensor and app custom-built for the Breezhaler device. This companion will provide patients with inhalation confirmation, medication reminders and access to objective data that can be shared with their physician in order to help them make better therapeutic decisions.

"Today’s news is a key milestone in our journey to reimagine asthma care by bringing innovative medicines and a digital companion to patients with uncontrolled asthma," said Linda Armstrong, MD, Respiratory Development Unit Head, Novartis Pharmaceuticals. "Once-daily IND/GLY/MF has the potential to improve asthma control for patients whose lives are still impacted by their disease, despite existing inhaled therapies. Additionally, we are pleased to bring an innovative sensor and app companion supplied with IND/GLY/MF to patients to help support enhanced adherence."

The CHMP recommendation is based on robust efficacy and safety data from over 3,000 patients with asthma from the Phase III IRIDIUM study, in which IND/GLY/MF demonstrated statistically significant improvements in lung function compared with indacaterol acetate/mometasone furoate (IND/MF).1

In the IRIDIUM study, the key secondary endpoint was improvement in Asthma Control Questionnaire score (ACQ-7) for IND/GLY/MF versus IND/MF. Both treatments delivered clinically meaningful improvements in this measure of symptoms from baseline at Week 26, but the key secondary endpoint was not met. Among other secondary analyses, IRIDIUM explored asthma exacerbation rates, where statistically significant reductions were observed in moderate-to-severe and severe asthma exacerbation rates with IND/GLY/MF compared with an established LABA/ICS standard-of-care (twice-daily salmeterol xinafoate/fluticasone propionate). Safety findings were consistent with the known safety profiles of the monocomponents.1

Last month the CHMP also recommended the approval of Atectura Breezhaler (IND/MF) as a maintenance treatment of asthma for adults and adolescents 12 years of age and older not adequately controlled with inhaled corticosteroids and inhaled short-acting beta-agonists.2 Novartis is committed to bringing IND/GLY/MF and IND/MF to patients, with additional regulatory filings currently underway in multiple countries, including Switzerland, Japan and Canada.

In keeping with the Novartis commitment to reduce the environmental impact of our asthma combinations, IND/GLY/MF and IND/MF will both be available in the Breezhaler device which is hydrofluoroalkane/chlorofluorocarbon (HFA/CFC)-free.

About Uncontrolled Asthma
Asthma affects an estimated 358 million people worldwide and can cause a significant personal, health and financial burden when not adequately controlled.3,4 Despite current therapy, over 40% of patients with asthma at Global Initiative for Asthma (GINA) Step 3, and over 45% at GINA Steps 4 and 5 remain uncontrolled.5,6 Patients with uncontrolled asthma may downplay or underestimate the severity of their disease and are at a higher risk of exacerbation, hospitalization or death.7,8,9 Barriers, such as treatment mismatch, safety issues with an oral corticosteroid and ineligibility for biologics, have created an unmet medical need in asthma.10,11

About Enerzair Breezhaler
Enerzair Breezhaler (QVM149; IND/GLY/MF) is intended as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year. This formulation combines the bronchodilation of indacaterol acetate (a LABA) and the antimuscarinic effects of glycopyrronium bromide (a LAMA) with mometasone furoate (high-dose ICS) in a precise once-daily formulation, delivered via the dose-confirming Breezhaler device. Glycopyrronium bromide certain use and formulation intellectual property were exclusively licensed to Novartis in April 2005 by Sosei Heptares and Vectura. Mometasone furoate is exclusively licensed to Novartis from a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA, for use in IND/GLY/MF (worldwide excluding the U.S.).

The sensor for the Breezhaler device was developed by Propeller Health and is a CE marked Medical Device, designed and licensed to Novartis exclusively for use with the Breezhaler inhaler worldwide. The sensor includes a microchip, a microphone, Bluetooth capabilities, an antenna and a battery. The sensor does not alter the drug delivery characteristics of the Breezhaler inhaler itself but produces a recording of each administered dose. Based on the patient’s recorded medication usage, personalized content is presented within the app to help the patient better self-manage their asthma.

About Atectura Breezhaler
Atectura Breezhaler (QMF149; IND/MF) is the combination of indacaterol acetate and mometasone furoate intended as a maintenance treatment of asthma in adults and adolescents 12 years of age and older not adequately controlled with ICS and inhaled short-acting beta-agonists. IND/MF combines the bronchodilation of indacaterol acetate (a LABA) with the anti-inflammatory mometasone furoate (an ICS) in a precise once-daily formulation, delivered via the dose-confirming Breezhaler device. Mometasone furoate is exclusively licensed to Novartis from a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA, for use in IND/MF.

About the PLATINUM Clinical Development Program
The PLATINUM program, containing over 7,500 patients worldwide, is the Novartis Phase III clinical development program supporting the development of IND/GLY/MF and IND/MF. It includes four studies: the QUARTZ study, which compared a low-dose of IND/MF with MF alone; the PALLADIUM study, which compared IND/MF with MF and salmeterol xinafoate/fluticasone propionate (Sal/Flu); the IRIDIUM study, which compared IND/GLY/MF with IND/MF and Sal/Flu; and the ARGON study, which compared IND/GLY/MF with a combination of Sal/Flu and tiotropium.

About the IRIDIUM study 1,12
IRIDIUM was a Phase III, multicenter, randomized, double-blind, parallel-group study, designed to compare the efficacy and safety of IND/GLY/MF with IND/MF in patients with asthma.

The purpose of the trial was to evaluate the efficacy and safety of two different doses of IND/GLY/MF (High: 150/50/160 ’g and Medium:150/50/80 «g), versus two respective IND/MF doses (High: 150/320 »g and Medium: 150/160 ’g) in patients with uncontrolled asthma, as determined by pulmonary function testing and effects on asthma control.

All patients were required to be symptomatic at screening despite being on treatment with medium or high stable doses of LABA/ICS. Approximately 3,092 male and female adult patients with asthma were randomized 1:1:1:1:1 (approximately 618 patients in each of the treatment groups) to receive either:

  • IND/GLY/MF 150/50/80 ’g (once-daily)
  • IND/GLY/MF 150/50/160 ’g (once-daily)
  • IND/MF 150/160 ’g (once-daily)
  • IND/MF 150/320 ’g (once-daily)
  • Sal/Flu 50/500 ’g (twice-daily, via Accuhaler )

The primary objective of this study was to demonstrate superiority of both high-dose IND/GLY/MF versus high-dose IND/MF and medium-dose IND/GLY/MF versus medium-dose IND/MF, all delivered once-daily, in improving trough FEV1 (volume of air that can be forced out in the first second of expiration approximately 24 hours post-administration of study drug) after 26 weeks of treatment in patients with asthma.

The key secondary objective was to demonstrate the superiority of both doses of IND/GLY/MF versus respective doses of IND/MF, in improving Asthma Control Questionnaire (ACQ-7) score after 26 weeks of treatment in patients with asthma.

Other secondary analyses also included reduction of exacerbation rate, comparing high-dose IND/GLY/MF with high-dose IND/MF and medium-dose IND/GLY/MF with medium-dose IND/MF. Secondary analyses included efficacy comparisons for both doses of IND/GLY/MF compared with Sal/Flu (50/500 ’g).

The study showed that IND/GLY/MF was superior to IND/MF in improving trough FEV1 after 26 weeks, meeting the primary endpoint. The key secondary endpoint, improvement in ACQ-7 score for IND/GLY/MF versus IND/MF was not met but tested treatments showed clinically meaningful improvements in this measure of symptoms from baseline at Week 26. Among other secondary analyses, a substantial reduction was observed in moderate-to-severe and severe asthma exacerbation rates with IND/GLY/MF compared with twice-daily Sal/Flu (50/500 g).

IND/GLY/MF was generally well tolerated, and safety was comparable across treatment arms.

Full information on all of the endpoints measured in the study can be accessed at ClinicalTrials.gov (Identifier: NCT02571777).

About the PALLADIUM study13
PALLADIUM (NCT02554786) was a multicenter, randomized, 52-week treatment, double-blind, triple-dummy, parallel-group study, designed to assess the efficacy and safety of IND/MF compared with MF alone in patients with asthma.

PALLADIUM included 2,216 male and female patients (including 107 adolescents, aged = 1.5.

Approximately 1,251 male and female patients with uncontrolled asthma (aged 18 and above) were randomized 1:1:1 (approximately 417 patients in each of the treatment groups) to receive either:

  • IND/GLY/MF 150/50/80 ’g (once-daily)
  • IND/GLY/MF 150/50/160 ’g (once-daily)
  • Open label Sal/Flu 50/500 ’g (twice-daily) delivered via Diskus plus tiotropium delivered via Respimat

The primary objective of this study was to demonstrate non-inferiority of both high-dose IND/GLY/MF and low-dose IND/GLY/MF to comparator Sal/Flu plus tiotropium after 24 weeks of treatment based on Asthma Quality of Life Questionnaire.

Secondary objectives included:

  • To evaluate efficacy of high-dose IND/GLY/MF and medium-dose IND/GLY/MF compared with Sal/Flu plus tiotropium based on trough FEV1 after 24 weeks of treatment
  • To evaluate efficacy of high-dose IND/GLY/MF and medium-dose IND/GLY/MF compared with Sal/Flu plus tiotropium based on Asthma Quality of Life Questionnaire over 24 weeks of treatment.
  • To evaluate efficacy of high-dose IND/GLY/MF and medium-dose IND/GLY/MF compared with Sal/Flu plus tiotropium based on ACQ-7 over 24 weeks of treatment.
  • To evaluate efficacy of high-dose IND/GLY/MF and medium-dose IND/GLY/MF compared with Sal/Flu plus tiotropium based on lung function over 24 weeks of treatment.

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