Novartis Will Not Support Further Development of Fevipiprant for Asthma

Novartis announced topline results from its pivotal global Phase III LUSTER-11 and LUSTER-22 studies exploring the efficacy and safety of the investigational oral, once-daily, DP2 receptor antagonist fevipiprant (QAW039). The pooled analyses of the LUSTER trials did not meet the clinically relevant threshold for reduction in rate of moderate -to-severe exacerbation compared to placebo over a 52-week treatment period for either of the doses (150mg / 450 mg). The studies included patients who had inadequately controlled moderate-to-severe asthma (GINA Steps 4 and 5) despite receiving inhaled mid-to-high dose corticosteroids (ICS) and at least one additional controller. The totality of these results do not support further development of fevipiprant in asthma.

Fevipiprant was generally well tolerated, with treatment-emergent adverse events generally balanced across groups and comparable to placebo. Detailed efficacy and safety data from the LUSTER-1 and LUSTER-2 studies are being analyzed and will be submitted for presentation at an upcoming medical congress.

"While the results of the LUSTER studies with fevipiprant are disappointing, they meaningfully contribute to our understanding of the DP2 pathway in asthma. We are incredibly grateful to all the patients, their families and the investigators who participated in the studies and contributed greatly to this research," said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis.

The pivotal replicate LUSTER-11 and LUSTER-22 studies are part of the VIBRANT Phase III program, which also includes the SPIRIT4 safety study and the supplemental replicate ZEAL-15 and ZEAL-26 studies. Topline results from ZEAL-1 and ZEAL-2 were announced in October 2019.

Novartis continues to invest into respiratory medicines with in-market products Xolair® (severe allergic asthma [SAA] and chronic spontaneous urticaria [CSU]), Ultibro® Breezhaler® (COPD), Phase III investigational products QVM1499 (moderate-to-severe asthma), and QMF14910 (moderate-to-severe asthma), as well as active research programs covering asthma, COPD and other areas of high unmet need, such as idiopathic pulmonary fibrosis and sarcoidosis.

Fevipiprant is an investigational, novel, steroid-free once-daily pill. It blocks the DP2 pathway, a potentially important regulator of the asthma inflammatory cascade.

LUSTER-1 and LUSTER-2 were 52-week, randomized, multi-center, double-blind, placebo-controlled, replicate Phase III studies in patients with moderate-severe asthma. The patient population included 894 (LUSTER-1) and 877 (LUSTER-2) patients aged ≥12 years, all of whom suffer from inadequately controlled moderate-severe asthma, receiving Global Initiative for Asthma (GINA) Steps 4 and 5 standard-of-care (SoC) asthma therapy: inhaled mid-to-high dose corticosteroids (ICS) and at least one additional controller. Recruitment was stratified based on blood eosinophil counts at Visit 1, so that approximately two-thirds of randomized patients had a blood eosinophil count ≥250 cells/μl and one-third had a blood eosinophil count <250 cells/μL, to determine the effect of fevipiprant across patients with varying eosinophil levels. Patients were randomized (1:1:1) to receive either fevipiprant 150 mg, fevipiprant 450 mg or placebo once daily.

The aim of these studies was to determine the efficacy, safety and tolerability of fevipiprant in addition to the current standard-of-care for severe asthma patients.

The primary endpoint for the replicate LUSTER-1 and LUSTER-2 studies was the reduction of the annual rate of moderate‐to‐severe exacerbations over a 52‐week treatment period in patients with moderate-to-severe uncontrolled asthma and high levels (≥ 250 cells/µL) of a type of white blood cell called eosinophils. The rate of reduction in all patients independent of blood eosinophil level was also studied as part of the primary endpoint.

 Secondary endpoints included change in asthma quality of life (as measured by the Asthma Quality of Life Questionnaire [AQLQ] for people 12 years and older), asthma control (measured via Asthma Control Questionnaire‐5), and lung function (measured via FEV1) over the 52‐week treatment period in patients with high blood eosinophil counts (≥250 cells/μl) and in all patients independent of blood eosinophil level.

 Safety of fevipiprant in terms of adverse events, electrocardiograms, vital signs and laboratory tests was also assessed.

 The severity of asthma ranges between mild, moderate and severe, with more severe asthma requiring more treatment (higher dose or stronger medication) to control symptoms and exacerbations. According to the the Global Initiative for Asthma (GINA) stepwise approach to asthma treatment, patients between Step 3 and Step 5 are considered moderate-to-severe.

 Despite the availability of standard-of-care asthma treatments for the moderate-to-severe asthma patients, over 45% at GINA Step 4 and 5 remain uncontrolled. These uncontrolled asthma patients often downplay or underestimate the severity of their asthma by tolerating their symptoms and accepting the severe impact of their disease on their quality of life. These patients are at an increased risk of experiencing a severe exacerbation, hospitalization, or death.

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