Novartis Announces Positive Phase III QUARTZ Trial Results for QMF149 in Asthma, Meeting Primary and Secondary Endpoints

Author: Zhixing

On May 30, 2019, Novartis announced that its Phase III clinical trial QUARTZ, evaluating QMF149 for the treatment of asthma, met both primary and secondary endpoints (FEV1 and ACQ-7). Compared with mometasone furoate monotherapy, treatment with QMF149 resulted in statistically and clinically significant improvements in patients’ lung function and asthma control.

The success of the QMF149 clinical trial serves as a precursor to Novartis’s blockbuster asthma product QVM149 (which recently demonstrated positive Phase II clinical results). QVM149 (IND/GLY/MF) is a triple-combination formulation comprising glycopyrronium bromide and QMF149, with market launch anticipated in 2020. Marketing authorization applications for both QVM149 and QMF149 have been submitted to the European Medicines Agency (EMA). The following provides a brief overview of QMF149 and its QUARTZ clinical trial.

Asthma

According to the Global Initiative for Asthma (GINA), asthma affects 300 million people worldwide, with a prevalence rate ranging from 1% to 18%. In recent years, the prevalence of asthma in China has shown a rapid upward trend, particularly among children. However, asthma control rates remain suboptimal both globally and in China. The rate of uncontrolled asthma among adults is 58.8% in the United States and 53.5% in Europe, while in China, the uncontrolled rate is as high as 59.5%.

Currently, there are many types of medications used in clinical practice for the treatment of asthma, primarily categorized into controller medications, such as inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), and reliever medications, such as short-acting β2-agonists.

However, asthma is a heterogeneous disease, and the lack of targeted therapies, coupled with the use of incorrect or ineffective medications, often results in poor disease control. For such patients, the development of novel drugs can offer improved strategies and options for the treatment and management of asthma.

QMF149

QMF149 is a once-daily, fixed-dose dual-combination formulation of a long-acting beta2-agonist (LABA) and an inhaled corticosteroid (ICS), developed by Novartis. It consists of indacaterol acetate (IND, LABA) and mometasone furoate (MF, ICS), administered via the Breezhaler inhaler. IND exerts a bronchodilatory effect on airway smooth muscle, while MF provides potent anti-inflammatory activity.

Phase III Clinical Trial QUARTZ

The QUARTZ study (NCT02892344) is a multicenter, randomized, double-blind, 12-week Phase III clinical trial evaluating the efficacy and safety of QMF149 Breezhaler (150/80 μg) compared with MF Twisthaler (200 μg) in adult and adolescent patients with asthma. The primary endpoint was forced expiratory volume in 1 second (FEV1), and the secondary endpoint was the Asthma Control Questionnaire-7 (ACQ-7).

Inclusion Criteria: Patients must have received stable, low-dose LABA/ICS or ICS therapy for at least 1 month. All enrolled patients must also receive twice-daily treatment with 100 μg of fluticasone propionate.

Enrolled patients: 802 patients with a mean asthma history of 14 years, including 64 adolescent patients (12 ≤ age < 18), were randomized 1:1 to receive once-daily QMF149 (n=398) or MF (n=404). The baseline FEV1 prior to treatment was 75%, and the majority of patients had previously received low-dose ICS (42.9%) or LABA/ICS (56.0%) therapy.

Primary Endpoints: After 12 weeks of treatment, 1) a statistically significant improvement in lung function as measured by FEV1, with the QMF149 group showing an increase of 0.182 L compared to MF (95% CI: 0.148, 0.217; p < 0.001); 2) a clinically meaningful improvement in lung function as measured by PEF, with the QMF149 group showing an increase in nighttime peak expiratory flow (PEF) of 26.1 L/min compared to MF (95% CI: 21.0, 31.2).

Secondary endpoint: After 12 weeks of treatment, asthma control assessed by the ACQ-7 showed not only a statistically significant improvement (−0.218; 95% CI: −0.293, −0.143; p < 0.001) but also a clinically meaningful improvement. According to the questionnaire results, 74.7% of patients in the QMF149 group achieved an ACQ-7 score improvement of ≥0.5, compared with 64.9% in the MF group (odds ratio: 1.69; 95% CI: 1.23, 2.33).

Safety Data: Both QMF149 and MF were well tolerated. Compared with MF, the QMF149 group had a lower incidence of adverse events (32.3% vs 38.3%), with over 90% being mild to moderate in severity. The rates of severe adverse events were 1.8% and 3.5% in the QMF149 and MF groups, respectively.

Summary: Compared with monotherapy MF, the fixed low-dose combination formulation QMF149 (IND/MF) can improve lung function and help control asthma in patients with asthma, and has good safety, providing a new option for asthma patients.

Reference Source:

Novartis' phase III QUARTZ study of new investigational inhaled combination treatment QMF149 meets primary and key secondary endpoints in patients with inadequately controlled asthma