AstraZeneca/Amgen's Potential First-in-Class Tezepelumab Receives CDE Clinical Trial Acceptance in China

On October 14, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) publicly announced that the clinical trial application for tezepelumab injection, a Class 1 novel biologic drug submitted by AstraZeneca and Amgen in China, had been accepted by the CDE. According to public information, this is a potential “first-in-class” new drug intended for the treatment of conditions such as asthma and atopic dermatitis. Previously, the product received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA). In addition, patient enrollment for its Phase 3 clinical trial has been completed, with results expected in the second half of 2020.

Screenshot source: CDE official website

Tezepelumab is a thymic stromal lymphopoietin (TSLP) inhibitor jointly developed by Amgen and AstraZeneca. According to public information from Amgen, this is a potential “first-in-class” novel drug. TSLP is an epithelial cytokine that serves as an upstream regulator of multiple inflammatory pathways in various diseases, including asthma, and plays a critical role in the initiation and persistence of airway inflammation.

Studies have shown that TSLP is highly active in regulating type 2 (T2) immunity. Meanwhile, it also plays a role in non-T2-driven inflammation by activating or signaling to various cell types, such as mast cells and basophils. Therefore, TSLP is considered a potential therapeutic target for a broad population of asthma patients. Blocking TSLP can prevent immune cells from releasing pro-inflammatory cytokines, thereby preventing asthma exacerbations and improving asthma control.

According to information on the official website of China’s Center for Drug Evaluation (CDE), AstraZeneca first submitted an Investigational New Drug (IND) application for tezepelumab in early 2018, which was accepted by the CDE. This marks the second time that an IND application for this product has been submitted in China. According to the Chinese Clinical Trial Registry and Information Publicity Platform, tezepelumab is currently undergoing two clinical trials in China, namely:

· An international, multicenter, Phase 3 clinical trial evaluating the efficacy and safety of tezepelumab in subjects with poorly controlled severe asthma;

· A Phase 1 study to evaluate the pharmacokinetics, safety, tolerability, and immunogenicity of a single subcutaneous dose of tezepelumab in healthy Chinese subjects.

According to the Phase 2b PATHWAY clinical trial, three different doses of tezepelumab were evaluated as add-on therapy for patients with a history of asthma exacerbations. The results demonstrated that low, medium, and high doses of tezepelumab significantly reduced the annualized asthma exacerbation rate across a broad patient population. Compared with the placebo group, the reductions were 61% (70 mg every 4 weeks), 71% (210 mg every 4 weeks), and 66% (280 mg every 2 weeks), respectively. Additionally, all three dose groups showed improvements in lung function, and asthma control was also improved at the two higher doses. In terms of safety, the incidence of adverse events was similar between the tezepelumab and placebo groups.

Based on the positive results of this trial, the U.S. FDA granted breakthrough therapy designation to tezepelumab for the treatment of patients with severe asthma. In an earlier press release issued by AstraZeneca, Dr. Jonathan Corren, principal investigator of the PATHWAY trial, stated that these trial results confirmed the hypothesis that TSLP is a key mediator of inflammation in severe asthma. Due to the activity of TSLP early in the inflammatory cascade, tezepelumab may be suitable for a broad population of patients with severe, uncontrolled asthma, regardless of patient phenotype or T2 inflammatory biomarker status.

It is important to note that approximately two-thirds of patients with severe asthma have type 2 (T2) inflammation-driven disease, including the eosinophilic phenotype, whereas currently available biologic therapies target only patients with T2-driven inflammation. The trial results for tezepelumab demonstrate its potential as a novel therapeutic option for a broader population of patients with severe asthma.

Currently, patient enrollment has been completed in the Phase 3 clinical trial evaluating tezepelumab for the treatment of patients with severe asthma whose symptoms remain uncontrolled. Results are expected in the second half of 2020. According to information on AstraZeneca’s official website, in addition to its use in severe asthma, tezepelumab is also being investigated in Phase 2 clinical trials for the treatment of patients with atopic dermatitis and chronic obstructive pulmonary disease (COPD).

Asthma is a chronic inflammatory airway disease characterized by a prolonged course and recurrent episodes. Patients typically present with symptoms such as wheezing, shortness of breath, chest tightness, and coughing. As the disease progresses, it can lead to irreversible airway narrowing and airway remodeling. Statistics indicate that there are over 300 million asthma patients worldwide. Among them, 10% suffer from severe asthma; these patients struggle to control disease symptoms even with high doses of standard asthma control medications and may require long-term use of oral corticosteroids (OCS). Severe, difficult-to-control asthma leads to patient debilitation, frequent asthma exacerbations, and severely limited lung function. Clinically, there is an urgent need for safe and effective new therapies to improve patient outcomes.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Oct 14, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2]Tezepelumab Significantly Reduced Asthma Exacerbations For A Broad Population Of Patients With Severe Uncontrolled Asthma. Retrieved September 7, 2018, from https://www.amgen.com/media/news-releases/2017/09/tezepelumab-significantly-reduced-asthma-exacerbations-for-a-broad-population-of-patients-with-severe-uncontrolled-asthma/

Source: Medical Insights

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