How to breathe life into respiratory drug development

Key takeaways:

• Care for COPD has consisted of combinations of previously used drugs for decades.
• Ensifentrine represents a novel inhaled compound.
• The stigma pertaining to personal responsibility in COPD needs to change.

We are currently experiencing a renaissance in the treatment landscape for respiratory disease, but we can do better.

When I first began my career in drug development more than 20 years ago, I had completed a doctorate in organic chemistry and a master’s degree in public health. I was eager to leverage my understanding of molecular behavior to develop novel inhaled therapies for a growing number of people in need.

However, while clinicians and researchers had achieved breakthroughs in other prevalent diseases affecting cardiovascular, metabolic and neurological systems, the field of respiratory health had largely remained centered around bronchodilators and corticosteroids, mechanisms that even 20 years ago had been around for a long time.

This dearth of innovation is particularly evident in COPD.

Despite affecting nearly 400 million people worldwide and being the third leading cause of death globally, COPD has seen no significant advances in drug development resulting in novel drug approvals in the past 2 decades.

Current treatment options primarily comprise combinations of existing drug classes, with the last 14 COPD therapies launched including drugs with the same mechanisms of action.

As chief development officer at Verona Pharma, a biopharmaceutical company dedicated to the treatment of chronic respiratory diseases, my focus is the development of novel therapeutics with pharmacology targeted toward disease mechanisms that will have a meaningful impact on patients’ disease burden and quality of life.

Pending approval with the FDA, one option on the horizon is ensifentrine, a novel inhaled compound developed by Verona Pharma.

This selective dual PDE3/4 inhibitor advances COPD treatment by combining bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona expects a decision from the FDA on the approval of ensifentrine before the end of June, with a launch soon afterward.

My hope is that the learnings from drug development for COPD and the demand by patients for a novel mechanism that helps them feel and function better will help reinvigorate the field of respiratory medicine and foster continued innovation.

In the meanwhile, there are three steps we can take to reach these goals.

Beyond blunt tools

First, we need to look beyond blunt tools to address COPD-specific mechanisms of disease.

Historically, patients with COPD have been treated with repurposed asthma medications, a practice that missed addressing the specific drivers of the disease.

For example, medications designed to alleviate type 2 inflammation, primarily associated with asthma, have been used to treat patients with COPD who predominantly experience type 1 inflammation.

This approach is problematic, as data indicate that such medications given to patients with COPD can result in limited clinical benefit and even lead to significant negative outcomes, including increased risk for pneumonia.

Furthermore, earlier intervention with appropriate treatments targeting chronic inflammatory processes active in patients with COPD could help prevent or delay progression of the disease.

Looking ahead, as research into respiratory diseases deepens, new therapies tailored not only to specific indications but also to subgroups of patients promise to enhance treatment efficacy and patient outcomes.

Unmet patient needs

Next, we need to focus on unmet patient needs.

More than 90% of patients with COPD experience daily symptoms despite regular maintenance therapy, which consists of long-acting bronchodilators and inhaled corticosteroids and combinations thereof.

In line with this, most patients with COPD report dissatisfaction with their current treatment options, highlighting a substantial demand for better solutions and an opportunity to redefine the standard of care.

I believe that for innovation to have a positive impact on patients, it should be driven by the mindset that addressing urgent unmet patient needs will drive acceptance of new therapies.

Change the COPD narrative

Finally, we need to change the narrative around COPD.

For many years, research funding for novel COPD therapies has been deprioritized. While various factors contribute to this trend, I believe that the stigma surrounding illness plays an important role.

In the early 2000s, COPD was strongly associated with smoking, fostering a mindset that blamed patients for their condition. Although smoking remains a major risk factor, the definition of COPD has broadened to include other inhaled insults such as air pollutants.

By changing the narrative of how morality and personal responsibility intersect with health, we can reduce the stigma that patients face and encourage more robust research and development. Recent societal shifts, such as the acceptance and rapid uptake of weight loss drugs, demonstrate a growing willingness to reconsider these views.

Coupled with the introduction of novel therapeutic options for COPD, this shift can inspire renewed efforts to understand and treat respiratory disease.

A turning point

Predicting the future, such as with drug development, is inherently precarious, but there are compelling reasons for optimism.

Enthusiasm within the biotech industry suggests we are not witnessing a fleeting moment but potentially a turning point in the treatment of COPD.

Our collective efforts hold great promise for transforming the treatment paradigm for COPD and significantly improving patient outcomes in the coming years.

For more information:

Tara Rheault, PhD, is the chief development officer at Verona Pharma.