From a Pulmonary fibrosis perspective, the ERS meeting in Amsterdam (27 September to 1 October, 2025) provided a combination of hope, challenge and satisfaction for the TherapeutAix team.
Hope was provided by the updates on the Fibroneer trials of Boehringer Ingelheim’s (BI) preferential PDE4B inhibitor, nerandomilast. After many years of negative clinical data and frustration within the field, this molecule shows promise as a standalone or in combination with nintedanib in the IPF and PPF populations. It was particularly exciting to see that this efficacy was maintained in the extension of the trial to 76 weeks. This data has supported the FDA approval of Jascayd, the first approval of an IPF therapy in over a decade.
As longstanding advocates of inhalation therapies for the treatment of ILDs, we were particularly pleased to see that treprostinil was both efficacious and well-tolerated in the TETON-2 trial.
Challenge was also provided by the Fibroneer, TETON-2 and other trials. It was apparent that patients treated with placebo alone fared better than those on placebo plus background therapy (pirfenidone or nintedanib). It seems likely that this observation is a consequence of differences in the patient population, particularly the disease duration, but this requires further consideration in future study design and interpretation. Interestingly, the Vicore open label AIR trial of the angiotensin II agonist, buloxibutid, utilised matched data and image analysis from Qureight to create a “real world” synthetic control cohort in demonstrating improved lung function and to support progression to a phase 2b placebo-controlled trial. This suggests that it may be possible to reduce the number of patients allocated to placebo groups, however, it seems likely that a “real time” placebo group will continue be required in future studies.
A further challenge is the burden of add-on therapy, with considerable increases in GI-related AEs being observed in the combination groups in the Fibroneer studies. This is reflected in the observation that the Quality of Life scores in the combination groups were reduced despite the improvement in disease-related endpoints, such as FVC decline. It is also worth noting that the nerandomilast-pirfenidone combination has been plagued by severe DDI issues.
Satisfaction was provided by seeing presentations reflecting significant progress by 5 clients where we have contributed to pre-clinical or early clinical strategy. Undoubtedly the hard work was by the respective teams but we are pleased to have been told that our input had a positive impact!