- Strong results from a mid-stage study suggest an experimental biologic treatment from AstraZeneca plc could offer a more comprehensive approach to treating severe asthma, potentially strengthening the British drugmaker's bid to build a leading portfolio of new respiratory medicines.
- In a Phase 2b study, tezepelumab reduced annual asthma exacerbation rates by between 61% and 71% compared to placebo and significantly lowered levels of multiple inflammatory biomarkers. The drug's broad effect suggests it could be used to treat more patients than other treatments already on the market.
- Unlike other asthma drugs, tezepelumab blocks a target thought to be a driver of several downstream inflammatory pathways. Inhibiting this cytokine, known as thymic stromal lymphopoietin or TSLP, could halt release of other inflammatory markers such as IL-4, IL-5 and IL-13.
Tezepelumab is one of three drugs AstraZeneca has flagged as future drivers of its respiratory business, particularly as biologic treatments begin to play a larger role in a market still dominated by inhaled medicines.
AstraZeneca and its development partner Amgen, Inc. believe tezepelumab is to be first in class, potentially opening up a new approach to treating severe asthma.
In the PATHWAY study, AstraZeneca tested three dosing regimens of tezepelumab, all of which showed a statistically significant reduction in the rate of annual asthma exacerbations. The trial focused on patients whose asthma remains uncontrolled despite receiving inhaled corticosteroids or long-acting beta-agonists — standard treatments for the potentially debilitating condition.
Tezepelumab also improved lung function and asthma control.
But further driving AstraZeneca's excitement was the drug's ability to drive down several biomarkers known to be connected to inflammation-driven severe asthma.
"In asthma patients, TSLP functions as an upstream epithelial ‘master-switch’ right at the start of the inflammation cascade," said Bahija Jallal, head of AstraZeneca's R&D subsidiary MedImmune, in a Wednesday statement. MedImmune led development of tezepelumab, as well as another asthma biologic currently in late-stage testing called benralizumab.
"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, including blood eosinophils, IgE and FeNO," Jallal explained further.
Those effects could position tezepelumab competitively, if subsequent studies corroborate the PATHWAY trial.
"Tezepelumab appears to be the broadest and most promising biologic for the treatment of persistent uncontrolled asthma to date," wrote Elisabeth Bel from the University of Amsterdam's Academic Medical Center in an accompanying editorial.
Bel cautioned, however, that the drug's safety profile is not fully established, citing three serious drug-related adverse events seen in the trial. While overall adverse event rates between tezepelumab and placebo were similar, Bel said concerns remained about the drug's potential risk of infections.
Other new biologic drugs for asthma, such as GlaxoSmithKline plc's Nucala (mepolizumab) and Teva Pharmaceutical Industries Cinqaero (reslizumab), have recently won approval as add-on treatments. And Sanofi SA and Regeneron Pharmaceuticals, Inc. are testing their closely watched dermatitis drug Dupixent (dupilumab) in asthma as well.
Jefferies analyst Michael Yee, however, thinks tezepelumab could compete, noting the drug's effect in PATHWAY "looks above expectations and nicely competitive and on higher end efficacy range for new asthma drugs."
AstraZeneca did not detail plans for next steps, such as a Phase 3 trial, although results of the study will be presented more fully at the ERS International Congress in Milan on September 12.
Shares in the British pharma were up nearly 5% in Thursday morning trading.