Pexopiprant

Gossamer Bio announced today that its two studies examining GB001 – the Phase IIb LEDA trial in eosinophilic asthma and Phase II TITAN trial in chronic rhinosinusitis – failed to meet their primary endpoints. Gossamer Bio announced today that its two studies examining GB001 – the Phase IIb LEDA trial in eosinophilic asthma and Phase II TITAN trial in chronic rhinosinusitis – failed to meet their primary endpoints. In the LEDA study, the primary endpoint, which was not met, was asthma worsening. However, the company noted that there were consistent and meaningful numeric reductions in the odds of asthma worsening compared to a placebo. “While we did not achieve statistical significance on the primary endpoint in the LEDA study, we are encouraged by the consistent results observed for all three doses of once-daily, oral GB001 therapy across the primary and secondary endpoints,” said Sheila Gujrathi, M.D., Co-Founder and Chief Executive Officer of Gossamer. “We believe these data provide important information for designing a well-powered Phase III program for GB001 in severe asthma. We plan to engage in global regulatory discussions in order to inform our thinking around potential partnerships or strategic alternatives for this program.” A total of 480 patients with uncontrolled, moderate-to-severe eosinophilic asthma were enrolled in the LEDA study. The company believes that the trial provided the opportunity to investigate subgroups based on clinical characteristics and biomarkers. Overall, Gossamer Bio is looking forward to discussing its findings with global regulatory authorities. “The results of the robust LEDA Study are meaningful and help us to further understand the DP2 pathway in asthma,” said Bruce Levy, M.D., Chief, Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School. “I believe GB001 as an oral treatment has the potential to serve the high unmet need of patients with uncontrolled severe asthma.” In the TITAN trial, 97 patients with chronic rhinosinusitis with and without nasal polyps were enrolled. Neither the primary or secondary endpoints were met. However, the safety and tolerability of GB001 at 40mg was generally consistent with what was observed in the LEDA study. GB001 is a highly selective oral antagonist of the DP2 pathway. The investigational, once-daily tablet is being developed as an add-on maintenance treatment for moderate-to-severe uncontrolled asthma. One drug that has shown promise on the asthma front as of late is Dupixent (dupilumab) from Regeneron Pharmaceuticals, Inc. and Sanofi. The companies announced results today from the Phase III trial examining dupilumab for the treatment of uncontrolled moderate-to-severe asthma, specifically in children aged six to 11 years. According to the data, the drug helped reduce the rate of severe asthma attacks in subjects over the course of a year, compared to a placebo. In addition, the participants appeared to show improved lung function at 12 weeks, compared to a placebo. Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. “Children with uncontrolled moderate-to-severe asthma often struggle to breathe, largely because of their impaired lung function, and this can have a serious impact on a child’s quality of life. It not only reduces their ability to participate in day-to-day activities, but can also take a huge emotional toll on the child and their family,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. “Dupixent is the only biologic shown in a controlled Phase III trial to improve lung function in children, which is generally consistent with results seen in the adolescent and adult trials. These positive data are especially encouraging for younger children who are struggling to manage their uncontrolled 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). 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 DP 2 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 DP 2 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 DP 2 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 DP 2 antagonists, although Novartis’ Tsai did indicate the failures led to a greater understanding of the DP 2 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. hbspt.forms.create({ portalId: "4413123", formId: "a126e976-bca0-4c13-aa9b-02e8feb92096" });