Are we entering the era of biologics for COPD

 In 2023, the pharmaceutical industry will mark 20 years since the first biologic approved to treat asthma was Xolair, an anti-IgE antibody. Since then, several biologic antibodies for asthma that target the inflammatory cytokines IL-4, IL-13, and IL-5 have been approved by the US FDA, EMA, and other agencies.

The treatment of both asthma and COPD Pipeline Drugs Market is the primary focus of methods like bronchodilator inhalers. However, this is not the case with therapeutic biologics. In stark contrast, the COPD pharmaceutical landscape has no biologic approvals, whereas the asthma pharmaceutical landscape has several approved biologics.

According to the Global Initiative for Chronic Obstructive Lung Disease, COPD is the third leading cause of death worldwide and affects approximately 384 million people.

In COPD clinical programs around the world, at least six different biologics are being studied in Phase III trials. By the middle of 2023, the results of a Phase III trial utilizing Dupixent (dupilumab), an IL-4/IL-13 monoclonal antibody (mAb) developed by Sanofi and Regeneron Pharmaceuticals, are anticipated.

Patients with COPD have access to options like bronchodilator inhalers, but these have limitations. According to Dr. Ian Adcock, Professor of Respiratory Cell and Molecular Biology at the National Heart and Lung Institute, Imperial College London, "bronchodilators are palliative in that they relieve the symptoms of the disease and do not target the underlying biology."

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Adcock continues, "Biologics have the potential to influence disease-causing processes if we hit the right target in the right patient." Biologics, in contrast to bronchodilators, offer COPD patients opportunities for disease modification.

Biologics: From COPD to asthma?

Cytokines play a crucial role in the regulation of an allergic phenotype, the immunoglobulin E (IgE) response, and cell-mediated inflammation, according to research. In the UK, asthma biologics have even been designated as a Rapid Uptake Product, a designation intended to encourage greater adoption and expansion of effective innovations.

Adcock asserts, "The introduction of biologics in the treatment of severe asthma has revolutionized therapy for patients with evidence of Type 2 (T2) inflammation." Type 2 inflammation is characterized by frequent exacerbations necessitating treatment with antibiotics or steroids or hospitalization, high blood eosinophil counts, and exhaled nitric oxide.

Adcock elaborates, "On the other hand, using this treatable trait (blood eosinophils and nitric oxide) has not proven successful in COPD." Other COPD biology-targeting biologics have also failed, indicating a significant knowledge and treatment gap.

David Pettigrew, CEO of digital therapeutics developer my mhealth, which has developed asthma and COPD biologic solutions, states, "However, despite around 20% of severe asthma patients having uncontrolled disease, only a relatively small fraction of these eligible patients are currently on biologics." According to Pettigrew, my mhealth has observed the divergent approaches to treating the two conditions because asthmatics now have access to biologics and COPD patients are waiting for their approval. It aims to increase consistency in how patients are evaluated for treatment eligibility and effectiveness and to assist patients and their clinicians in optimizing their therapy.

Tezspire, or tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody manufactured by AstraZeneca, became the most recent biologic to receive FDA approval as an additional treatment for severe asthma patients without phenotype or biomarker restrictions in December 2021. Nevertheless, patients require a patient-centered approach. For instance, not all patients with severe asthma and evidence of Type 2 inflammation respond effectively. A Phase II COPD study involving Tezspire (NCT04039113) is currently under investigation and is scheduled to conclude in March 2024. According to the findings of this study, patients with COPD have elevated levels of the pro-allergic cytokine TSLP in their serum and bronchial mucosa.

Improved comprehension of the effectiveness of biologics There have been a number of attempts to introduce biologics to COPD. The application for FDA approval of GSK's Nucala (mepolizumab) for COPD was rejected in 2018. The US Pulmonary Allergy Drugs Advisory Committee rejected its use as an addition to inhaled corticosteroid-based maintenance with three votes in favor and 16 against. Patients based on their blood eosinophil counts were intended to use Nucala. The committee concluded that the demonstrable data did not support the biologic's approval due to its inadequate risk-benefit profile.

Benralizumab from AstraZeneca's Fasenra was also unsuccessful in Phase III trials that year. The primary endpoint, which was a statistically significant decrease in COPD patients' exacerbations, was not met by the trial.

However, the effectiveness of biologics for COPD has evolved in recent years.

Pettigrew states that biologic COPD treatments "also showing great promise." However, the company is currently collaborating with its pharmaceutical partners and COPD userbase of 33,000 patients to assist in the analysis of the available data because these are still in the clinical trial stage.

According to a spokesperson for Roche for the media, Nathalie Altermatt, "[Now], years of research are culminating in breakthroughs that may ultimately enable personalised therapies that go beyond just managing symptoms to actually treat the underlying disease." Astegolimab, the company's anti-IL33 antibody, is the subject of a Phase III trial for COPD patients (NCT05595642), which is expected to conclude in 2025. On the other hand, a Phase II trial (NCT05037929) is anticipated to conclude in 2024.

Continued efforts AstraZeneca has continued its Fasenra development program despite the initial setback, which is currently progressing in the Phase III Resolute trial (NCT04053634). Clinical evidence from the Phase III program's responder analysis indicates that Fasenra reduced exacerbations in a subset of COPD patients with specific clinical characteristics and elevated blood eosinophil counts.

Tozorakimab, an IL-33 mAb, is another biologic being developed by the British company for COPD in a Phase III Titania trial (NCT05158387). Tozorakimab has been shown clinically to block IL-33 signaling through two distinct pathways: the ST2 receptor pathway, which is associated with inflammation, and the non-ST2 pathway, which is associated with tissue remodelling by reducing inflammation and epithelial dysfunction.

It has been demonstrated that the anti-IL-33 route, which Roche is also taking, drives a variety of inflammatory responses. According to Altermatt, "In patients with moderate-to-severe COPD, astegolimab has the potential to reduce the various types of inflammatory responses associated with disease exacerbation."

Are COPD biologics available?

Industry players anticipate this to happen soon. If biologics for COPD are found to be effective and safe, we can anticipate a flurry of results over the next few years, ushering in a new era of COPD treatment options. However, we might have to wait longer than we initially anticipated.

Individual-driven treatments may be the turning point for biologics for COPD. According to Adcock, the first three clinical trials utilizing anti-IL-5 antibodies for the treatment of asthma were unsuccessful because they included all participants and did not differentiate between patients who were most likely to respond. Adcock continues to assert that COPD research is currently investigating "the use of specific biomarkers to direct biological therapy to selected patients rather than all comers," which "improves the number of people who will give a clinically significant response."