touchRESPIRATORY coverage from ERS 2025:

Chronic obstructive pulmonary disease (COPD) exacerbations are a major driver of disease progression, healthcare utilization, and mortality, with respiratory viral infections being the most common trigger, predominantly rhinoviruses. In this interview, we caught up with Dr Sebastian L Johnston (National Heart and Lung Institute, Imperial College London, London, UK) to discuss the aims, design and findings from the phase 2a study investigating vapendavir for the treatment of COPD patients infected with rhinovirus.

The abstract “Vapendavir for the treatment of COPD patients challenged with rhinovirus: A phase 2a placebo-controlled study” was presented at ERS 2025, 27 September–1 October, Amsterdam.

The main burden of disease in COPD, on top of the chronic disease itself, is acute attacks of COPD, which often lead to hospitalizations, GP consultations, antibiotic courses, steroid courses, and indeed mortality. Frequent exacerbations or attacks are also associated with longer term disease progression and decline in lung function. Nowadays, a major focus of any COPD treatment is to try and prevent or ameliorate the severity of these acute attacks to reduce healthcare costs. Most of the costs associated with managing COPD relate to these acute attacks, with hospitalization being the most expensive. These acute attacks are mostly precipitated by common cold virus infections. Numerically, the most dominant are rhinoviruses, which are, if you like, the common cold virus family and they precipitate at least half of acute attacks of COPD, if not more than half.

Vapendavir is a direct-acting, anti-rhinovirus, antiviral drug. This blocks rhinovirus replication and, therefore, should reduce the severity of rhinovirus infection induced diseases, common cold, but also acute attacks of chronic lung diseases, such as COPD.

Vapendavir has actually been around for a long time, it’s been around for over 20 years. During early development, it had problems with study design, and it also had problems with dosing and getting high enough drug levels. So it sat on the shelf, not being developed for several years since the last company closed having had a negative study in asthma.

Vapendavir has now been acquired by Altesa Biosciences Inc and has been reformulated, so that you do get high drug levels and good antiviral activity. It seemed obvious to go into COPD as the first indication, as it has the greatest burden of disease associated with rhinovirus infection. I mentioned asthma already, acute attacks of asthma are also precipitated by rhinovirus infections, but the disease burden associated with COPD is greater. COPD has a greater unmet medical need in my view and most of my colleagues’ views, so we decided to go for COPD as the first indication. If successful, we’ll follow up with asthma and other chronic lung diseases too.

This was a proof-of-concept study giving rhinovirus infections to people with COPD to precipitate acute attacks; hopefully, mild-to-moderate rather than severe attacks. We didn’t want to put anyone in the hospital and, thankfully, we didn’t. It’s a pretty unique model, giving rhinovirus infections to people with COPD. We’ve now given rhinovirus infections to over a hundred people with COPD, and we’ve shown that it reproduces the acute attacks that happen naturally.

So this was a proof-of-concept study to try to show that vapendavir does indeed ameliorate the severity of rhinovirus induced worsening of COPD. We aimed to recruit around 50 subjects and we ended up with twenty subjects in each group (active versus placebo), who were successfully infected, developed symptoms, and did get randomized to treatment or placebo. So the analysis was on those 40 subjects, 20 in each group, who were successfully infected and treated. It is important to note that participants only started treatment after they had developed symptoms of acute infection, thus mimicking use during naturally occurring attacks.

The safety was very good. We had no increased adverse effects with the drug compared with placebo. In fact, the adverse effects were less common with the drug than placebo because most of the adverse effects were related to the infection that we had given people, which the drug made better.

In terms of efficacy, vapendavir reduced symptom severity and it hastened time to recovery back to baseline. It improved measures of lung function, which are important in COPD exacerbations. It also accelerated virus clearance, and we’re just in the process of analysing inflammatory markers in blood and have some initial results that look very encouraging.

We’re also looking at whether secondary bacterial infections will be reduced by this drug, and those analyses are ongoing. But we’re hopeful that if you treat a rhinovirus infection, one of the beneficial outcomes will be that you reduce secondary bacterial infections and therefore antibiotic use, which can only be a good thing.