The two trials were evaluating the drug for reducing the rate of moderate-to-severe exacerbations compared to placebo over a 52-week period for inadequately controlled moderate-to-severe asthma (GINA Steps 4 and 5).
Switzerland’s Novartis announced that its LUSTER-1 and LUSTER-2 Phase III trials of fevipiprant for asthma failed to meet their clinically relevant endpoints. As a result, the company indicated it is halting the developing of the drug for asthma.
Fevipriprant is a novel, steroid-free once daily pill that blocks the DP2 pathway, which regulates the inflammatory cascade in asthma. The two trials were evaluating the drug for reducing the rate of moderate-to-severe exacerbations compared to placebo over a 52-week period for inadequately controlled moderate-to-severe asthma (GINA Steps 4 and 5). The asthma was uncontrolled despite patients taking inhaled mid-to-high dose corticosteroids and at least one other controller.
The drug was typically well tolerated.
“While the results of the LUSTER studies with fevipiprant are disappointing, they meaningfully contribute to our understanding of the DP2 pathway in asthma,” said John Tsai, head of Global Drug Development and chief medical officer of Novartis. “We are incredibly grateful to all the patients, their families and the investigators who participated in the studies and contributed greatly to this research.”
The LUSTER studies are part of the company’s VIBRANT Phase III program. That includes the SPIRIT safety study, and two supplemental ZEAL-1 and ZEAL-2 studies. The topline data from the ZEAL studies were presented in October 2019. The drug failed in those studies as well.
In the LUSTER studies, there were 894 patients in LUSTER-1 and 877 in LUSTER-2 aged 12 years or older who had inadequately controlled moderate-severe asthma and received standard-of-care therapy. The patients were classified based on blood eosinophil counts at the first visit so about two-thirds had a blood eosinophil count treater than 250 cells/µl and a third had counts less than 250 cells/ µl. Patients were then randomized 1:1:1 to receive either fevipiprant 150 mg, 450 mg or placebo.
The primary endpoint of both studies was the decrease of the annual rate of moderate-to-severe exacerbations for a year. A secondary endpoint was quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ) for people 12 years and older, asthma control, and lung function.
At this point, Amgen, AstraZeneca and Novartis have had failures in drugs that target the DP2 pathway. Another company, Gossamer Bio, has GB001, a DP2 antagonist, in several Phase II trials for moderate to severe eosinophilic asthma, chronic rhinosinusitis and one planned for chronic spontaneous urticaria. An interim readout on the asthma trial is expected in 2020. If the data is negative, it would undermine any potential for DP2 antagonists, although Novartis’ Tsai did indicate the failures led to a greater understanding of the DP2 pathway.
Novartis plans to share more complete data on the LUSTER trials at an upcoming medical conference. However, the company stated that they were killing the program because “the totality of these results do not support further development.”
Asthma ranges from mild, moderate and severe. Severe asthma requires more treatment. The Global Initiative for Asthma (GINA) classifies patients between Step 3 and Step 5 as moderate-to-severe. Even though standard-of-care treatment for this class of patients are available, more than 45% of patients at GINA Step 4 and 5 have uncontrolled asthma.
