Amgen and AstraZeneca announced that their Phase III NAVIGATOR trial of Tezepelumab hit the primary endpoint in severe asthma.
Amgen and AstraZeneca announced that their Phase III NAVIGATOR trial of Tezepelumab hit the primary endpoint in severe asthma. The drug with standard of care demonstrated a statistically significant and clinically meaningful decrease in the annualized asthma exacerbation rate (AAER) over 52 weeks compared to placebo plus standard of care.
Tezepelumab is a potential first-in-class human monoclonal antibody that targets and blocks thymic stromal lymphopoietin (TSLP), a key epithelial cytokine. TSLP is at the top of multiple inflammatory cascades and can cause an overreactive immune response in allergic, eosinophilic and other forms of airway inflammation associated with severe asthma. Eosinophils are a type of inflammatory white blood cell. Tezepelumab is a once-monthly injection.
The study showed that exacerbation rate reductions with tezepelumab in patients with both high and low levels of eosinophil counts. The demarcation is 300 eosinophils per microliter, and the data indicated the drug was effective in patients with higher levels, and levels below 300 cells per microliter, and even in patients with baseline eosinophil counts less than 150 cells per microliter.
“Due to the complex nature of asthma, many patients continue to face debilitating asthma despite receiving standard of care inhaled medicines and currently approved biologics,” said Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR trial. “Today’s ground-breaking results show that Tezepelumab has the potential to transform care for a broad population of severe asthma patients who are underserved today, including those without an eosinophilic phenotype.”
The drug was granted Breakthrough Therapy Designation in September 2018 for patients with severe asthma, without an eosinophilic phenotype. The data demonstrated in the trial, in patients with baseline eosinophil counts less than 300 cells per microliter, supports the designation.
The drug was well tolerated in patients diagnosed with severe asthma. Preliminary data did not find clinically meaningful differences in safety between the Tezepelumab and placebo cohorts.
The two companies agreed to collaborate in 2012. Earlier this year the companies updated their partnership, with plans to continue cost-sharing and profit-sharing after AstraZeneca pays a mid-single-digit royalty to Amgen. AstraZeneca leads the drug development process, while Amgen handles manufacturing. Both companies will jointly commercialize the drug, with Amgen handling sales in the U.S. and AstraZeneca handling sales in Canada. Amgen will handle sales outside the U.S. as collaboration revenue. Both companies’ shares climbed 4% in premarket trading.
David M. Reese, executive vice president of Research and Development at Amgen, stated, “We are absolutely thrilled with the topline results of the NAVIGATOR study in this broad population of patients with severe asthma, regardless of eosinophil count. Tezepelumab represents a potential new class of biologics that could enable us to treat severe asthma at the top of the inflammatory cascade, addressing a high unmet need among the millions of patients living with severe asthma throughout the world. Tezepelumab has the potential to revolutionize care with efficacy demonstrated even in patients with a low eosinophil count.”
NAVIGATOR and SOURCE are part of the Phase III PATHFINDER program, which builds on data from the Phase IIb PATHWAY trial. The program also plans mechanistic and long-term safety trials. Patients in the NAVIGATOR and SOURCE trials were eligible for the Phase III ESTINATION extension trial evaluating long-term safety and efficacy. The companies plan to present data at a future medical conference.
