Are you sitting comfortably? Do you notice your breathing, all nice and easy? Now, try taking a straw and breathing just through that. Not quite so easy is it? How about going to the kitchen to make a tea, still breathing through that straw, and sort out the laundry too whilst you are there. That is tougher to do. Now squeeze that straw, and, if you have stairs, try going up and down those a few times. You will probably find that almost impossible. Well, welcome to what every day feels like if you have Chronic Obstructive Pulmonary Disease (COPD), a common, progressive, and life-threatening respiratory disease without a cure. For most it is an invisible disease too, as the millions of people who suffer from it have been forced into a sedentary lifestyle as constant shortness of breath chronically reduces everyday activities. Even with maximum therapy, millions of patients continue to suffer from severe breathlessness and poor quality of life. As patient advocate Chris Warburton says (here), COPD ‘gradually squeezes the life out of you. Literally.’
In short, a breath of innovation is needed. This is where London’s Verona Pharma (AIM: VRP) (Nasdaq: VRNA) has been breezing ahead with its lead asset, ensifentrine (RPL554), a first-in-class, inhaled dual phosphodiesterase 3 and 4 (PDE3/4) inhibitor with both bronchodilator and anti-inflammatory effects. This dual inhibitor is being lined up for phase 3 clinical trials for use as a maintenance treatment, following the FDA’s general agreement on the program in May. This program builds on ensifentrine’s clinical work within COPD and other respiratory diseases, including asthma and cystic fibrosis. Ensifentrine has shown significant and clinically meaningful improvements in both lung function and COPD symptoms as well as a favorable safety profile in over 1,300 people.
The company recently hosted a panel discussion where a trio of leading US respiratory clinicians spoke about the urgent need for a new COPD treatment with a different mechanism of action that better addresses symptoms and offers greater patient benefit. Ensifentrine’s nebulised formulation, provides direct delivery of the medicine to the lungs, which can be a big benefit for frailer patients that may struggle to operate handheld devices.
The three experts were Dr. James F. Donohue, MD, Emeritus Chair and Professor of Medicine, Chief of the Division of Pulmonary and Critical Care Medicine, University of North Carolina; Dr. Donald A. Mahler, MD, Emeritus Professor of Medicine at Geisel School of Medicine at Dartmouth; and Dr. Jill Ohar, MD, Professor of Internal Medicine, Pulmonary, Critical Care, Allergy, and Immunological Diseases, Wake Forest School of Medicine.
The panel talked about how, in the US, over 1.2 million COPD patients remain symptomatic despite maximum therapy. COPD is a global silent epidemic. Dr Ohar said, ‘The idea of a new drug that is going to be both a bronchodilator as well as an anti-inflammatory agent is extremely exciting and something that there is a true unmet need for.’ Dr Mahler explained how ‘Fatigue is also another important symptom… which leads to anxiety and depression… people worry that it will put a strain on their family.’ Dr Donahue added, ‘We just don’t have enough [therapy] options… it’s an excellent [Phase 3] design, [which] has a very good chance of getting [ensifentrine] approved.’
Verona is planning to start later this year a duo of pivotal phase 3 clinical trials with nebulised ensifentrine in 1,600 moderate to severe, symptomatic, COPD patients in the US and Europe. These pivotal trials are called ENHANCE-1 and ENHANCE-2, with ENHANCE being an acronym derived from Ensifentrine as a Novel inHAled Nebulised COPD thErapy. The randomized, double-blind, placebo-controlled Phase 3 programme, which is subject to Verona securing additional financing, has two elements. ENHANCE-1 involves 800 patients in a 24-week treatment period with a cohort of patients being treated for 48 weeks to show long-term safety. ENHANCE-2, which will also include 800 patients, is identical but involves just the 24-week treatment period. Both studies will evaluate efficacy and safety of twice daily nebulised ensifentrine as monotherapy or as an add-on to standard of care treatment with a single bronchodilator. The primary endpoint for each study will be the standard test of how much air a patient can breathe out in a set time-period (technically referred to as FEV1 (forced expiratory volume in one second) over 12 hours). What sets ensifentrine apart from existing drug classes used to treat COPD, including corticosteroids, beta2-agonists and anti-muscarinics, is its ability to provide dual inhibition, combining bronchodilator and anti-inflammatory properties in one compound.
Now, take the straw out, and breathe normally again. That feeling of overwhelming relief as oxygen blissfully floods your lungs is what COPD patients are dreaming of, and what clinicians hope ensifentrine will deliver. To give an idea of the potential major impact of a new innovative therapy on the treatment of COPD, consider that, according to the American Lung Association (here), COPD is the third leading cause of death by disease in the United States. More than 16.4 million people have been diagnosed with COPD, but millions more may have the disease without even knowing it. Providing new treatments to fight the silent epidemic of COPD would be breath-taking innovation, delivered.