Novartis has finally abandoned its late-stage asthma drug candidate fevipiprant following another Phase III trial failure.
The pooled analyses of the LUSTER 1 and LUSTER 2 trials, which were investigating fevipiprant in patients with inadequately controlled moderate-to-severe asthma, did not meet the clinically relevant threshold for a reduction in the annual rate of exacerbations (asthma attacks) compared to placebo.
Fevipiprant is a novel, steroid-free, orally-administered, once-daily prostaglandin D2 receptor 2 (DP2) receptor antagonist that targets the inflammatory cascade. It was previously hailed as a potential game-changer following promising results in a small trial of 61 patients with moderate-to-severe asthma. In this study, the drug was associated with reduced eosinophilic inflammation, improved lung function, and enhanced quality of life relative to placebo.
If approved, fevipiprant would have become the first pill to be marketed for asthma in 20 years, with researchers previously expressing enthusiasm for its potential to reduce reliance on inhalers, oral steroids, and costly biologics.
However, doubts were raised in October 2019 when fevipiprant failed to the meet the primary endpoint for improvement in forced expiratory volume in one second (FEV1), a measure of lung function, in two Phase III trials conducted in patients with moderate asthma: ZEAL 1 and ZEAL 2. Novartis initially appeared to dismiss this result as an anomaly, suggesting that fevipiprant would likely fare better in the core registration LUSTER trials, which included patients with more severe forms of asthma. This was based on the assumption that, as DP2 activation increases with disease severity, patients with greater disease severity would be more likely to respond to the drug. However, following the disappointing results from the LUSTER studies, the company has eventually confirmed that the development of fevipiprant in asthma will be discontinued.
Novartis is not the only company to feel the effects of this setback. Shares in Gossamer Bio, which has a lead drug candidate with a similar mechanism of action to fevipiprant, fell following Novartis’ recent announcement.
GlobalData (2019) Frontier Pharma: Asthma and Chronic Obstructive Pulmonary Disease: Asthma Ahead of COPD in Terms of Innovation with the Focus on Targeted Biologic Therapies for Severe Disease Phenotypes, GDHC492FP