COPD: the world’s biggest neglected disease?

We speak to Verona Pharma’s CEO Jan-Anders Karlsson to find out how the company is looking to tackle the challenges of COPD, a surprisingly overlooked disease.

The World Health Organization predicts that Chronic Obstructive Pulmonary Disease (COPD) will become the third leading medical cause of death worldwide by 2030, but the disease doesn’t get the same level of attention as other therapeutic areas and treatments remain lacking.

UK-based biotech Verona Pharma is one company hoping to tackle these challenges in COPD. The company’s investigational compound ensifentrine has reported positive results in phase 2 trials in a nebulised formulation with phase 2b trials ongoing and plans to enter Phase 3 in 2020. Jan-Anders Karlsson, the company’s CEO, tells us more.

What are some of the biggest challenges in the COPD disease space today?

We have a hard time getting the message out that millions of COPD patients are suffering in silence. In the US alone, there are about 30 million patients. There's very little media coverage around the disease, and few support organisations in comparison to other disease areas with serious unmet needs.

How can you get that message out there?

The patient support groups are important. If you look at the Cystic Fibrosis Foundation in the US, they have really helped the cystic fibrosis community get to the forefront of scientific discussion and debates around treatments. They have been extremely successful in helping to get treatment to patients in the US.

Despite efforts from the patient support organisations for COPD in the US and  Europe the disease is not well known and patients do not have an adequate voice. This is partly because the patients tend to be older and have difficulties with accomplishing everyday tasks, so it’s slightly different from diseases that affect parents or younger people.

We work with these foundations and do our utmost to communicate that a lot of patients really need something new and different and that the industry and these foundations are here to help.

Why isn't much attention given to COPD?

COPD is set to become the third leading cause of mortality in the world. It used to be seen as a smoking-related disease that was self-inflicted, but smoking is not the only cause of COPD. Air pollution and inhalation of fumes, including from burning biomass, in workplaces and at home are also causes. Especially in India and China, air pollution is a major contributor to the number of cases of the disease.

COPD is a major cost for society with US total annual medical costs projected to rise to $49 billion in 2020. It’s in the interests of everybody to understand, prevent, and treat the disease.

What is the landscape like for COPD treatments at the moment?

Today you have two types of bronchodilators. Inhaled drugs that open the airways – beta 2 agonists and antimuscarinics – were first used in the 60s and 70s and are still around today. They’re short-acting rescue medications and can be taken five or six times a day. After them came the long-acting versions of those drugs, which are the most prevalent medications for COPD today.

Now combination treatments, with two drugs in one inhaler, are becoming increasingly common. One inhalation gives you the two compounds in an active dose at the same time. It can be taken once a day.

The other drug we have is inhaled steroids, which can be used in combination with a bronchodilator for COPD patients.

This is very similar to asthma treatment – in fact, the different COPD treatments came from asthma drugs. In the 80s one definition of COPD was that you didn't really benefit from asthma treatment. When we talked about COPD back then, he view was that we shouldn’t develop COPD drugs because it’s self-inflicted and nobody will pay for them. But eventually those views changed – people realised that a market existed and we could really help patients.

Another available drug is a phosphodiesterase type 4 inhibitor which you take once a day and can prevent hospitalisation from exacerbations, but it also comes with side effects that can be very difficult for patients.

So there aren’t many types of treatments available today. The evolution has been more towards convenience and how many times a day you need to take a drug.

The biggest question for treatment is should you start a patient on two bronchodilators straight away? In addition, some people are pushing for triple-action treatment. The dilemma with a triple is that inhaled steroids don't work well in many COPD patients. They should not be used by patients that are not severely sick and are not having exacerbations or frequent hospitalisations. But there is nothing else available to treat these severely ill patients until they receive oxygen. That's the dilemma for the physicians. They are really looking for a new type of treatment that can open up the airways, dampen the inflammation and reduce symptoms.

What are the biggest unmet patient needs you are trying to address with nebulised ensifentrine?

The largest unmet medical need is patients that are treated with two or three drugs  but are still symptomatic and continue to lose lung function with time.

They come to a point that even when they have treatment, they're still not able to get around the breathlessness and they can't really function. They progress towards oxygen treatment and then there's nothing more we can do.

That decline in some patients is very fast, but in others it’s a little slower. We think those patients that really have nowhere else to go need something different. That's where we think a new treatment with a different mechanism of action like ensifentrine, which is a dual PDE3/4 inhibitor combining bronchodilator and anti-inflammatory properties in one compound, would really make a difference. It is also important that ensifentrine is well tolerated and can be combined with existing classes of treatments.

In the US, the latest numbers show that there are now almost three million patients on dual and triple treatment. So that’s three million people who have possibly already progressed to maximum therapy. From our market research, it seems that about 40% of these patients, or 1.2 million are still symptomatic even if they're on dual and triple therapy. That’s a lot of patients and a burden on the health care system and hospitals, not to mention caregivers and families.

We believe ensifentrine can help patients that are in that desperate situation by opening up their airways, dampening the inflammation in the lungs and reducing symptoms like breathlessness and coughing – because that's what bothers them the most – and so improve their quality of life.