Patients with severe and uncontrolled asthma who took tezepelumab had significantly lower annual asthma exacerbation rates than those on placebo, according to the latest results of the PATHWAY Phase 2b trial.
The study, “Tezepelumab in Adults with Uncontrolled Asthma,” appeared in the New England Journal of Medicine. It was also the subject of an oral presentation, “Efficacy and safety of tezepelumab in adults with severe asthma: A randomised Phase II Study,” given during the recent ERS International Congress 2017 in Milan, Italy.
Tezepelumab, formerly known as AMG157, was developed by AstraZeneca‘s MedImmune unit in collaboration with Amgen. It is an antibody that blocks the activity of thymic stromal lymphopoietin (TSLP), a pro-inflammatory signaling protein.
TSLP is produced in response to pro-inflammatory stimuli, including allergens and viruses in the lung. When this protein interacts with its receptor on the surface of immune T-cells, it triggers a cascade of signals that cause several inflammatory molecules to be produced. This mechanism is crucial in lung inflammation and asthma symptoms, making it an attractive potential therapeutic target.
The PATHWAY trial (NCT02054130) aimed to assess tezepelumab’s efficacy and safety. It included 584 patients with moderate to severe asthma who were randomly assigned to receive one of the three tested dose regimens of tezepelumab: 70 mg every four weeks (low dose), 210 mg every four weeks (medium dose), or 280 mg every two weeks (high dose) — or a placebo.
Patients also received inhaled corticosteroids or long-acting beta-agonists with or without additional asthma controller medicines.
Upon 52 weeks of follow-up, the investigators reported that all tezepelumab-treated patients significantly reduced their annual asthma exacerbation rate. When compared to the placebo-treated group, patients taking low doses of tezepelumab reduced their exacerbation rate by 61 percent, whilethose taking medium doses saw their rates fall by 71 percent, and those on high doses reduced their exacerbation rate by 66 percent.
“In asthma patients, TSLP functions as an upstream epithelial ‘master-switch’ right at the start of the inflammation cascade. By binding to TSLP, tezepelumab impacts multiple downstream inflammatory pathways associated with asthma, as shown by striking reductions in the level of multiple biomarkers in the PATHWAY trial,” Bahija Jallal, executive vice president and head of MedImmune, said in a press release. “This broad biomarker response is unprecedented among respiratory biologics and reflects our commitment to leading respiratory science for unmet medical needs.”
The investigational therapy was also shown to improve lung function — regardless of the dose regimen — and to help control asthma symptoms with the two higher dose regimens.
“These efficacy results strongly confirm that TSLP is an important mediator of inflammation in severe asthma.” said Dr. Jonathan Corren of UCLA’s David Geffen School of Medicine, and principal investigator of the PATHWAY trial.
Overall, the treatment was safe, with a similar frequency of adverse events as those on placebo. The most common among them were asthma, inflammation of the nose and pharynx, headaches, and inflammation of the bronchi.