Amgen (NASDAQ:AMGN) and AstraZeneca (NYSE:AZN) today announced results from the PATHWAY Phase 2b trial of tezepelumab that showed a significant reduction in the annual asthma exacerbation rate compared with placebo in patients with severe, uncontrolled asthma. Tezepelumab is a novel anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody being developed by MedImmune, AstraZeneca’sglobal biologics research and development arm, in collaboration with Amgen.
The trial results were published today in the New England Journal of Medicine (NEJM), and will be followed by an oral presentation at the European Respiratory Society (ERS) International Congress 2017 in Milan on Sept. 12, 2017.
The PATHWAY trial achieved its primary efficacy endpoint, showing annual asthma exacerbation rate reductions of 61 percent, 71 percent and 66 percent in the tezepelumab arms receiving either 70 mg or 210 mg every four weeks or 280 mg every two weeks, respectively (p<0.001 for all comparisons to placebo). In the trial, tezepelumab was given as an add-on therapy to patients with a history of asthma exacerbations and uncontrolled asthma despite receiving inhaled corticosteroids/long-acting beta-agonists with or without oral corticosteroids (OCS) and additional asthma controllers.
Significant and clinically meaningful reductions in the exacerbation rate were observed independent of baseline blood eosinophil count or other type 2 [(T2) referred to as Th2 in the NEJM publication] inflammatory biomarkers. Tezepelumab also demonstrated improvements in lung function at all doses and in asthma control at the two higher doses (p<0.05 for all comparisons to placebo). The incidence of adverse events was similar between the tezepelumab and placebo groups. The most common adverse events (≥5 percent) in tezepelumab-treated patients were asthma, nasopharyngitis, headaches and bronchitis.2 Future studies in large populations of patients will be important in confirming the results demonstrated in this trial.
“These efficacy results confirm the hypothesis that TSLP is an important mediator of inflammation in severe asthma,” said Jonathan Corren, M.D., David Geffen School of Medicine, UCLA and Principal Investigator of the PATHWAY trial. “Due to its activity early in the inflammatory cascade, tezepelumab may be suitable for patients with both T2 and non-T2 driven asthma, including those ineligible for current biologic therapies which only target the T2 pathway.”
“The responses seen with tezepelumab in the PATHWAY trial show promise for a novel therapeutic option with the potential to impact multiple downstream inflammatory pathways associated with asthma,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We are committed to leveraging our deep understanding of inflammatory pathways to develop innovative treatments that address significant unmet medical needs.”
TSLP is an upstream epithelial cytokine that drives multiple inflammatory pathways in various diseases, including asthma. TSLP is active in the regulation of T2 immunity; however, it may also play a role in non-T2 driven inflammation by activating or signaling to many types of cells, such as mast cells, basophils, natural killer T cells, innate lymphoid cells and neutrophils.3-7 Therefore, TSLP has been identified as a potential therapeutic target across a broad asthma population.
Filed Under: Drug Discovery