YouRui Pharma Successfully Launches Phase III Trial of First-in-Class COPD Drug Ensifentrine in China, Accelerating Specialty Respiratory Pipeline Development
VCBeat has learned that Yourui Pharmaceutical, a biopharmaceutical company focused on innovative respiratory medicines, administered the first dose in its Phase III Ensifentrine ENHANCE-CHINA clinical trial on April 6, 2023. The trial is for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in mainland China.
On April 7, 2023, the national investigators’ meeting for the Phase III clinical trial of Ensifentrine, a novel drug for the treatment of chronic obstructive pulmonary disease (COPD), known as ENHANCE-CHINA (Study No.: RPL554-CPC001) and sponsored by Yourui Pharmaceutical, was grandly held in Guangzhou, China. More than 100 investigators from 46 research centers across the country attended the event.
Ensifentrine is an investigational, potential global first-in-class inhaled dual phosphodiesterase (PDE) 3/4 inhibitor. Its dual inhibition mechanism enables a single compound to simultaneously achieve bronchodilation and anti-inflammatory effects. This therapeutic profile has the potential to alleviate respiratory symptoms such as dyspnea and cough, while also providing anti-inflammatory benefits for patients with chronic obstructive pulmonary disease (COPD).
Review of the Clinical Trial Progress of Ensifentrine in China (Source: Yourui Pharmaceutical)
Ensifentrine’s dual-inhibition mechanism enables a single compound to simultaneously achieve bronchodilation and anti-inflammatory effects, highlighting its distinct advantages over existing COPD therapies. In addition to chronic obstructive pulmonary disease (COPD), Ensifentrine is being investigated in multiple countries for other indications, including asthma and cystic fibrosis. It can be administered via diverse delivery devices—such as nebulizers, inhalers, dry powder inhalers (DPIs), and metered-dose inhalers (MDIs)—to achieve therapeutic efficacy, underscoring its significant blockbuster potential.
In 2021, Yourui Pharmaceutical entered into an exclusive agreement with Verona Pharma (Nasdaq: VRNA) to obtain the rights for the development and commercialization of Ensifentrine in the Greater China region, including mainland China, Hong Kong (China), Macao (China), and Taiwan (China). Yourui Pharmaceutical is responsible for the subsequent registration, launch, and commercialization of Ensifentrine in China.
On December 20, 2022, Verona Pharma announced that the two pivotal global Phase III clinical trials of ensifentrine, a novel nebulized dual PDE3/4 inhibitor for maintenance treatment of COPD, ENHANCE-1 and ENHANCE-2, both successfully met their prespecified primary and key secondary endpoints.
Existing clinical outcome data show that in the ENHANCE–1 trial, the rate of exacerbations in patients with moderate-to-severe COPD was reduced by 40% over 24 weeks compared with the placebo group (p=0.0012); in the ENHANCE–2 trial, the risk of exacerbation—defined as the time to first exacerbation—in patients with moderate-to-severe COPD was reduced by 41% compared with the placebo group (p=0.0008). The safety profile was favorable, with very few adverse events occurring in more than 1% of subjects and at a higher incidence than in the placebo group.
Based on this,Verona Pharma Announces Plans to Submit New Drug Application (NDA) for Ensifentrine to the U.S. FDA in Q2 2023。
Following the announcement, Verona Pharma’s stock trading volume reached 17.9832 million shares on the 20th, with a 37.81% surge, marking nearly ten consecutive days of gains and setting a new all-time high since the company’s listing.
Verona Pharma’s milestone progress in advancing the ensifentrine pipeline has validated the drug’s feasibility in clinical treatment and bolstered confidence in Yourui Pharmaceutical’s clinical trials in China. Meanwhile, the significant stir caused by Verona Pharma in the secondary market reflects the high level of societal attention currently focused on treatments for chronic obstructive pulmonary disease (COPD). Given the urgent clinical need for COPD therapies, ensifentrine is poised to enter a vast and promising “blue ocean” market.
Globally, respiratory diseases rank among the top five causes of death, with chronic obstructive pulmonary disease (COPD) being the predominant type. As one of the three major chronic diseases, COPD has an incidence rate second only to cardiovascular disease and diabetes. However, constrained by factors such as health education, the awareness rate of COPD in China is less than 10%, leading to a significant underestimation of the patient population by both society and the healthcare industry.
According to "Prevalence and Risk Factors of Chronic Obstructive Pulmonary Disease in China (China Pulmonary Health [CPH] Study)" published in The Lancet[1] Research findings indicate that the total number of adults with COPD in China has exceeded 100 million, accounting for approximately one-quarter of the global patient population. The prevalence of COPD among adults (aged ≥20 years) is 8.6%, rising to 13.7% in those aged over 40 years and exceeding 27% in individuals aged over 60 years. The prevalence is significantly higher in men than in women (11.9% vs. 5.4%). Only 12% of COPD patients reported having undergone prior pulmonary function testing.
China has a substantial demand for COPD medications; however, given that the disease results from interactions between genetic factors and various external influences, drug development is highly challenging, and no safe and effective targeted therapies are currently available.
“Inhibiting inflammation-induced mucous hyperplasia of epithelial cells” and “alleviating airway collapse” are currently the main research directions for COPD., the R&D strategy involves oxidative stress (preclinical stage: nuclear factor E2-related factor 2/Nrf2), protease versus antiprotease imbalance (cathepsin G/CG vs. proteinase 3/PR3), necrosis and autophagy (preclinical stage: endoplasmic reticulum chaperone GRP78), among other aspects. Currently, the most rapid progress is being made in the development of drugs targeting inflammatory mediators (targets include: CXCR2, CCR1, and 5-LO) and PDE inhibitors.
Ensifentrine, a dual PDE3/4 inhibitor that simultaneously achieves bronchodilation and anti-inflammatory effects, is the most competitive COPD-specific therapeutic candidate in the current pipeline and is poised to become the first of its kind to reach the market.With its overseas clinical trials reaching endpoints and the initiation of Phase III clinical trials in China, Ensifentrine is expected to benefit COPD patients worldwide within the next year.
For Yourui Pharmaceutical, which specializes in niche specialty drugs for respiratory diseases, it is not only accelerating the domestic development of Ensifentrine, a global first-in-class innovative drug, but also possesses multiple respiratory drug pipelines with significant competitive advantages.
Currently, Yourui Pharmaceutical’s innovative drug pipeline for respiratory diseases—including chronic obstructive pulmonary disease (COPD), neonatal respiratory distress syndrome (NRDS), respiratory syncytial virus (RSV) infection, and allergic rhinitis—has entered clinical trial and commercialization stages, with rights covering China, South Korea, and various countries and regions in Southeast Asia.
Among these, Bentrio™ nasal spray, designed for personal protection against airborne viruses and allergens, was launched in Hong Kong (China) in November 2022, marking the first product to substantively realize UroGen Pharma’s commercialization rights in the Asia-Pacific region. In the same month, the China Phase III clinical trial of MVA-BN RSV, a vaccine for the prevention of respiratory syncytial virus (RSV) in the elderly, was approved by the Center for Drug Evaluation (CDE), positioning it to potentially become the first RSV vaccine marketed in the Asia-Pacific region.
Yourui Pharmaceutical is dedicated to the Asia-Pacific specialty drug market, with a focus on promoting innovative respiratory pipelines. Leveraging a dual-engine model of “R&D + commercialization,” the company maintains robust cash-generation capabilities and will continue to address unmet medical needs in the local market.
References:
[1]Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health[CPH] study): a national cross-sectional study. Lancet. 2018 Apr 28; 391(10131): 1706-1717.