Amgen Tezepelumab BLA Submitted to U.S. FDA

Amgen (NASDAQ:AMGN) today announced its partner AstraZeneca (NASDAQ:AZN) submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for tezepelumab, a potential first-in-class medicine in severe asthma. The submission is supported by positive clinical trial results from the PATHFINDER clinical program including the pivotal NAVIGATOR Phase 3 trial, which demonstrated a statistically significant and clinically meaningful reduction in the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma compared to placebo. Tezepelumab is the only biologic to consistently and significantly reduce AAER in a broad population of severe asthma patients irrespective of the baseline eosinophil counts across Phase 2 and Phase 3 clinical trials.

“Severe asthma remains uncontrolled for many patients despite current therapies for this complex and often debilitating condition,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “This submission brings us one step closer to providing this potentially transformative treatment option to a broad population of severe asthma patients, across phenotypes and irrespective of biomarkers.”

Tezepelumab targets and blocks the action of an epithelial cytokine called thymic stromal lymphopoietin (TSLP) which plays a key role across the spectrum of asthma inflammation. In NAVIGATOR, tezepelumab demonstrated exacerbation rate reduction irrespective of baseline eosinophil count and  improvements in lung function measurements, asthma control and health-related quality of life compared to placebo. The most frequently reported adverse events for tezepelumab were nasopharyngitis, upper respiratory tract infection and headache. These results support the FDA Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.

Data from the tezepelumab development program will be presented at upcoming scientific meetings including the American Thoracic Society 2021 International Conference later this month.

About Severe Asthma
Globally, there are approximately 2.5 million severe asthma patients who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many severe asthma patients have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control. Uncontrolled asthma occurs when symptoms persist despite treatment. Severe uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life. Patients with severe uncontrolled asthma have twice the risk of asthma-related hospitalizations. There is also a significant socio-economic burden, with these severe uncontrolled asthma patients accounting for 50% of asthma-related costs.

Multiple inflammatory pathways are involved in the pathogenesis of asthma. Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma. These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO). However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation, and may not qualify for or respond well to a current biologic medicine.

NAVIGATOR and the PATHFINDER Clinical Trial Program
Building on the positive Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR and SOURCE. The program includes additional planned mechanistic and long-term safety trials.

NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in 1,061 adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS. NAVIGATOR met the primary endpoint with tezepelumab added to SoC demonstrating a statistically significant and clinically meaningful reduction in the AAER over 52 weeks in the overall patient population, compared to placebo added to SoC. The trial also met the primary endpoint in the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER in that patient population. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.

NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting TSLP. The U.S. Food and Drug Administration Breakthrough Therapy Designation was granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype. The U.S. Food and Drug Administration Breakthrough Therapy Designation was granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype. Tezepelumab is being developed by AstraZeneca in collaboration with Amgen (see AstraZeneca and Amgen collaboration below).

SOURCE is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. In the trial, patients were randomized to receive tezepelumab 210 mg every four weeks or placebo as add-on therapy, with patients maintained on their currently prescribed ICS plus LABA, with or without other asthma controller therapy.

Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long term safety and efficacy.