Common denominators in fibrotic lung disease

Common denominators in fibrotic lung disease
June 15, 2020 theraaixadsf418
model of lung

With fibrotic disease being one of our areas of interest, it has been highly interesting to follow the news in the past six months or so around nintedanib. It is one of only two approved drugs for idiopathic pulmonary fibrosis, IPF.

IPF continues to be a focus area for drug development. Even though its root cause remains elusive, it is an indication that is well defined, has precedence in clinical development, and, despite approved therapies, remains an indication with high unmet medical need for patients.

IPF can be classified within the larger group of fibrotic interstitial lung diseases (ILDs), and there is debate in the field whether ILD should be considered a single disease or not. A key implication of the answer to the question is that, if there is a shared pathophysiology across ILD indications, a single drug should work in more than one, or all, of them. Alternatively, if specific ILD indications have different pathologies with different disease drivers, different drugs could be required for each.

Against this background, and after being approved in IPF, nintedanib has been studied in other ILDs. In the SENSCIS trial, nintedanib was studied in patients with ILD due to systemic sclerosis (SSc-ILD).  The INBUILD trial included patients across a broad range of chronic fibrosing ILDs with a progressive phenotype. Indications evaluated in this trial included ILD associated with connective tissue disease, such as rheumatoid arthritis, SSc, dermatomyositis/polymyositis, mixed connective tissue disease, Sjögren’s syndrome, and even anti-synthetase syndrome. In both Phase III trials, patients were treated for 52 weeks with lung function (forced vital capacity, FVC) as the primary outcome parameter. In both trials, nintedanib significantly slowed the decline in FVC and preserved lung function, earning this drug additional approvals by the FDA and EMA for SSc-ILD. It also received a positive CHMP opinion for a third indication, treatment of other chronic fibrosing interstitial lung diseases with a progressive phenotype.

Obviously, nintedanib’s effectiveness in these indications is welcome news for patients and physicians, and it’s interesting to speculate what this means for drug development in this field. Are the different ILDs really ‘one and the same’?  – Or did the broad set of targets for nintedanib, which include the PDFG, VEFG and FGF receptors as well as a number of tyrosine kinases, enable this drug to address different drivers for different diseases?

At TherapeutAix, we will continue to be engaged in fibrotic lung diseases to help develop drugs that can address the remaining unmet medical need in this field, and help clients work towards therapeutic options that completely halt, or reverse, fibrotic remodeling. With our network, we can build platforms of evidence in this field that are based on human tissue and enabled by biomarker readouts to define the right development goals.

In addition, we are pioneering accessible open innovation workshops to set up efficient and value-generating clinical development programmes for your compounds. Please get in touch to start a discussion.