Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia with an unknown cause that progresses gradually, primarily affecting the elderly. The presence of fibrosis has significant implications for individuals with reduced lung compliance, resulting in decreased quality of life and limited survival. Although the exact mechanism remains unclear, researchers have investigated various factors, such as senescent telomerase replication and abnormal lung stem cell differentiation, to understand the root cause. Extensive research has consistently shown that IPF is closely linked to the dysfunction of alveolar epithelial cells. Current scientific studies on IPF cover a range of aspects including oxidative stress, endoplasmic reticulum stress, mitochondrial damage, and iron-induced apoptosis. By examining these mechanisms, a comprehensive model has been developed that explains the process of IPF. Oxidative stress is identified as the primary trigger, followed by mitochondrial damage as a central component, leading to the mesenchymal transformation of alveolar epithelial cells as the ultimate outcome. This model is expected to serve as a valuable reference for understanding the mechanism of IPF and guiding future drug development efforts.
Fibrosis is defined as the excessive accumulation and disorganized deposition of extracellular matrix components, affecting any organ in the human body. Fibrotic diseases of the vital organs such as lung, heart, kidney and liver can be chronic, progressive, irreversible and fatal. Although fibrotic diseases account for 45% of the mortality in the Western world, the available treatment options are limited in numbers, efficacy and safety. There is certainly a lack of progress in developing novel anti-fibrotics even though the market size for fibrotic diseases is estimated to be ~$30B and several pharmaceutical companies have active R&D programmes in this field. We reviewed the current efforts in developing novel anti-fibrotic medicines focusing on lung, heart, kidney, liver and skin fibrosis. Our analysis revealed an estimated 83% attrition rate from Phase 2 to Phase 3 trials across the five fibrotic diseases. The possible reasons for the slow pace and high attrition rates in developing new anti-fibrotics are discussed and potential solutions are proposed.
