Reflections from ERS

Having joined a wide range of sessions at the virtual ERS meeting last week, we were keen to share some of our reflections. Despite the virtual format there was still a huge amount of information, so we have decided to limit this to just 4 take-home messages that we came away with. 

What’s next in COPD?

When working with clients with projects/assets with potential to treat respiratory diseases, COPD is always one of the areas considered. However, it is becoming harder to imagine how opportunities for new modalities can be realised. An area of focus at ERS was the pros and cons of triple (LABA/LAMA/ICS) versus dual (LAMA/LABA, LABA/ICS) inhaled therapy and the introduction of single inhaler triple therapies, with a particular focus on which patients will benefit from inclusion of ICS. It is clear that the opportunity for new approaches will be further squeezed if these existing therapies are used more effectively, through improvements in adherence and persistence of use. This will place an increasing burden of proof on the pharmacology and translational package to support the potential for a differentiated positioning.   

The theme of improved disease control through technological enhancements of inhalers to improve adherence and persistence was also picked up during the 2nd Annual Inhalation and Respiratory Drug Delivery Online Conference. Not surprisingly, much discussion focused on the fact that many enhancements are associated with an increase in cost and potential environmental impact. There was also a reminder that, to achieve reimbursement, improvements in adherence must translate to improved outcomes. It will be interesting to see how the control/cost/sustainability dynamic evolves over the next few years.  

Vicious viral circle 

It was sobering to have reinforced the cruel symmetry associated with viral infections and lung disease. Viral infections in early childhood can lead to a life-long decrement in lung development and function which, in later life, can result in a predisposition to COPD. In turn, COPD is associated with an increase in the likelihood of poor clinical outcomes in patients with COVID-19. A similar relationship is observed with severe asthma and COVID-19 outcomes but, importantly, asthma control can reduce the risk. As with the COPD discussion above, it seems that there is still scope to optimise the use of “old” pharmacological approaches to achieve asthma control and reduce the risks associated with viral infections. 

Fibrosis = fibrosis = fibrosis?

Given the times are what they are, there were quite a few discussions about respiratory effects of COVID-19. One of the more immediate consequences of severe infection is fibrotic remodelling of the lung. It has long been described that, following mechanical ventilation, fibrosis is building up and severely impacts come patients after respirator weaning. Induction of fibrotic remodelling after SARS-CoV-2 infection in the same patients is compounding the problem. 

We have commented on this earlier on our blog, and it’s still to early to tell, but those patients seem to have a quite different pathophysiology compared to patients with progressive fibrotic disease, like IPF or SSc-ILD. It will be interesting to see whether these disease entities allow to discern drugs that inhibit profibrotic activity versus drugs that are ‘true antifibrotics’ and able to reduce established fibrosis, which – at least conceptually – should be much more feasible to do against the background of a stable disease. 

ILD – defining the disease and future therapies 

Idiopathic pulmonary fibrosis (IP) has received a great deal of attention at the ERS since the launch of the current standards of care (SOC), Pirfenidone and Nintedanib, nearly 8 years ago. More recently, and certainly at this ERS, attention has moved to the wider area of interstitial lung diseases (ILD), driven in part by trials of the SOCs in ILD (e.g., SENCIS and INBUILD trials), together with a greater understanding of their pathophysiology.  

The definition ILD covers a range of diseases, both with a fibrotic and what appears to be “mixed” fibrotic-inflammatory phenotype.  The former includes IPF, chronic hypersensitive pneumonitis (HP), asbestosis and others; the latter connective tissue ILD, SSc-ILD and several other “unclassifiable” ILDs.  We learned that early diagnosis of ILD is really needed. Diagnostic delay, due to a variety of factors (no early symptoms, poor clinical skills, long waiting times) is associated with poor prognosis.  Biomarkers may help with this and identify those patients who will progress quickly and those with low risk of progression.   

However, molecular and genetic biomarker (clinical) studies have not been conclusive, and the majority studied so far appear to lack reproducibility.  However, two have emerged from correlation studies – MMP7 and CA125 (MUC16) which reflect matrix turnover and epithelial function, respectively. These are considered “good to go” for clinical trial use. Recent genetic studies have demonstrated that short telomeres are associated with a poor prognosis.  However, CT scan remains the “gold standard” biomarker.  

The approach to the treatment of IPF is now well-established with the current drugs, Pirfenidone and Nintedanib, despite their shortcomings. No doubt new anti-fibrotic treatments will emerge to address these. But what about ILD?  Clinical experience indicates a patient population with a progressive, fibrotic ILD, that are unresponsive to current anti-fibrotic SOCs.  This phenotype overlaps with CT-ILD, HP and other ILD populations.  A treatment paradigm appears to be emerging for these groups. This involves “first line” treatment with anti-inflammatory/immunomodulatory drugs (established, such as AZT, prednisolone; or new, such as Tociluzimab), and if not effective, “second line” treatment of antifibrotic, alone or in combination with an immunomodulatory drug. This paradigm will no doubt evolve with clinical use, and as new therapeutic approaches arise from over 30 clinical trials ongoing in IPF and ILD.  

It will be also interesting to see how these approaches will be developed and extended to other ILDs which do not appear to have a fibrotic phenotype.    

With considerable expertise in respiratory diseases and inhalation projects, we’re optimally suited to support your project. To learn more, and about or free-of-charge project assessment, don’t hesitate to contact us!

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