Chronic Obstructive Pulmonary Disease (COPD) is a group of long-term progressing disorders involving emphysema and chronic bronchitis. The conditions usher in a gradual obstruction of airflow in and out of the lungs, resulting in an increasingly arduous breathing process with prominent symptoms of breathlessness, persistent cough, wheezing, and chest tightness. The disease affects a significant population globally, some of which remain undiagnosed. The analysts at DelveInsight estimate in a report “Chronic Obstructive Pulmonary Disease (COPD) - Market Insight, Epidemiology and Market Forecast – 2032” that there were 35.6 million diagnosed prevalent cases in the 7MM (the US, EU4 countries (Germany, France, Italy, Spain) and the UK, and Japan) in 2022. The US comprised 18 million cases in the same year.

Various treatment modalities broadly involve lifestyle modification and smoking cessation, pulmonary rehabilitation, oxygen therapy, and therapeutic interventions. The therapeutic options can be divided into monotherapy, double combination, and triple combination therapies. The treatment goals are to reduce the symptoms and risks of exacerbations and improve health status and exercise tolerance.

There are currently few treatment options to treat COPD, and the need for alternative, safe, and effective treatments for COPD remains unmet. Several key players are working to develop new mechanisms for better COPD management to fill the existing gaps. Of the major players, Verona Pharma, EpiEndo Pharmaceuticals, and Sanofi are marching ahead with their assets.

Verona Pharma presented an additional analysis of Phase 3 ENHANCE-1 Study in COPD at ERS International Congress 2023 titled, “Inhaled Ensifentrine, decreased healthcare research utilization, and reduced moderate exacerbation rate and risk in COPD over 24 weeks.” Verona Pharma has been active with ensifentrine as an investigational first-in-class investigational drug candidate under review by the FDA for the maintenance treatment of COPD. Verona’s ensifentrine has three main mechanisms of respiratory disease: bronchiectasis, anti-inflammatory effect, and increased mucus clearance. This is the first drug that combines bronchodilator and anti-inflammatory effects in COPD.

This Phase III candidate is in trials for the maintenance of COPD treatment as a monotherapy and in combination with LAMA through a nebulization route of administration. The presentation highlighted the data related to the reduction in exacerbation rate and risk associated with moderate to severe COPD. Additionally, it provided the impact assessment of ensifentrine on healthcare utilization while demonstrating the reduction in the overall disease burden. Analyzing the market’s prospects, the drug has the potential to outsell COPD triple therapy. The selective dual inhibitor of phosphodiesterase 3 and 4 enzymes showed favorable results.

On the same lines, abstracts reviewing several Sanofi collaboration Investigational products and treatments will be presented at the International Congress of the European Respiratory Society (ERS) 2023 in Milan, Italy, which also includes Dupixent (dupilumab) COPD data. Late Breaking Abstract on Efficacy and Safety of Dupilumab for COPD with Type 2 Inflammation Indicated by Elevated Eosinophils and Oral NEJM/ERS Joint Journal Session on Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts will be the pivotal COPD programs to look forward to in this year’s ERS. With several biologics under development for COPD, Duplimab is at the forefront of the COPD biologics landscape.

The company will be presenting the results from the Phase III Dupixent (BOREAS) trial that showed significant improvements in annual exacerbation rates, lung function, and quality of life, as symptoms of COPD along with new analysis show a reduction in systemic corticosteroid use in adult patients with uncontrolled COPD with evidence of type 2 inflammation. Safety results from the COPD trial were generally consistent with the known safety profile of Dupixent in its approved respiratory indications.

Dupilumab has the potential to influence the vicious cycle of exacerbations and lung function decline in COPD patients with type 2 inflammation and at high risk of exacerbations who are already on optimal inhaled triple therapy by blocking the common receptor component of interleukin-4 and interleukin-13. COPD patients with type 2 inflammation experienced rapid and lasting disease improvement after treatment with the monoclonal antibody dupilumab. Duplimab is the first biologic to improve clinical outcomes in COPD patients.

EpiEndo Pharmaceuticals showcased the latest research on the lead asset EP395 in COPD titled, “PA599: EP395 effect on cell diapedesis measured by intravital microscopy”. EpiEndo is taking a new approach to drug development for chronic respiratory diseases, focusing on using Barriolide compounds. The drug candidate is an orally administered azithromycin derivative. The clinical trial (NCT05572333) plans to recruit up to 60 participants, 45 or older, who have been diagnosed with COPD for at least 2 years. Although the trial is not yet recruiting, it will be conducted at half a dozen sites in the UK and Germany. The first results of the trial are expected in the second half of 2023. Data from a previous Phase I trial (NCT04819854), conducted in healthy volunteers, demonstrated that EP395 is generally safe and well tolerated with its pharmacological properties consistent with once-daily dosing. EP395 will be administered to COPD patients for the first time in a Phase IIa trial. This double-blind, randomized, placebo-controlled trial will evaluate the safety and tolerability of EP395, as well as its effects on lung function, inflammation, and barrier strengthening. Other measures include heart function and patient quality of life.

Progressively, EpiEndo’s EP395 aims to become the first oral macrolide on the market capable of reducing antibiotic resistance, helping to strengthen the protective barrier and fight inflammation in the treatment of COPD.

While EpiEndo’s EP395 is too nascent to be calibrated, direct competition is on the horizon with Ensifentrine vs. Duplimab. Verona Pharma faces considerable risks, primarily clinical and regulatory, as Ensifentrine has not yet received approval, and several clinical trials are still underway. There is also a competitive risk because Verona Pharma is a maiden launcher, which could cause sales to grow more slowly than market expectations. However, Ensifentrine has a clear advantage over Duplimab. With dual bronchodilators and anti-inflammatory effects, ensifentrine has many applications for moderate to severe COPD patients and can support a higher price tag than current nebulizers in the market.

In both anticipation and apprehension, there is a lot to be answered in COPD. Based on DelveInsight’s analysis, the COPD market in 2022 was estimated to be USD 12.5 billion in the 7MM, which is likely to surge at a considerable CAGR in the forecast period. Given the size of the COPD market and the limited effective treatment options, every coming treatment is crucial to transform the treatment paradigm.