Breathe, breathe in the air: the anti-CCN2 antibody pamrevlumab (FG-3019) completes a successful phase II clinical trial for idiopathic pulmonary fibrosis

Abstract

Pirfenidone and nintedanib have been approved for idiopathic pulmonary fibrosis (IPF) due to their ability to statistically slow, over a year, the rate of decline in lung forced vital capacity (FVC), neither drug has been reported to have o positive effects on high-resolution computed tomography (HRCT) of the chest, symptoms, or quality of life. Moreover, pirfenidone and nintedanib have substantial gastrointestinal tolerability issues. Overall, these data highly suggest that novel therapeutic approached are needed. CCN2 has been shown to be a mediator of fibrosis in many preclinical models. Anti-CCN2 strategies are in clinical development for IPF, A recent study by Richeldi and colleagues described the recent Phase II clinical trial for FG-3019 in IPF, and the results were highly encouraging. This commentary contextualizes and summarizes these exciting findings.

Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma

“…CTGF, a primary interactor of TGF-β, is also profibrotic, and inhibition of CTGF in cultured human LC cells using the monoclonal antibody FG-3019 blocked ECM synthesis in these cells [ 37 ]. The antibody FG-3019, or pamrevlumab, is currently being evaluated in clinical trials for idiopathic pulmonary fibrosis, but its effectiveness beyond cultured cells in glaucoma has not yet been illustrated [ 258 ]. While intriguing, there are also a multitude of other potential therapies or pathway targets of TGF-β that could be beneficial for the treatment of glaucoma [ 259 ].…”

Idiopathic pulmonary fibrosis: Current and future treatment

“… 126 In PRAISE a randomized, double‐blind, placebo‐controlled phase 2 clinical trial, 103 IPF patients age 40 to 80 years were split into 2 groups, 50 received the drug, while 53 were given the placebo every 3 weeks for 48 weeks in total. 127 , 128 Of the original 103 patients, 78 (38 on pamrevlumab and 40 on placebo) completed the study. Pamrevlumab safely and effectively slowed lung function decline in IPF patients with mean change from baseline to week 48 in percentage of predicted FVC of −2.9% in the pamrevlumab group compared with a change of −7.2% in the placebo group.…”

Emerging role of CCN family proteins in fibrosis

“…It has been showed that FG-3019 suppressed the early progression of muscle fibrosis in a rat model (Barbe et al, 2019 (Leask, 2019(Leask, , 2020Richeldi et al, 2020…”

“…Of note, it is found that FG‐3019 acted by blocking the fibrosis‐related decrease of CCN3 expression (Barbe et al, 2020). Currently, FG‐3019 is being fast‐tracked by the US FDA as a potential therapeutic drug intervention, which is in Phase III clinical trials for IPS and pancreatic cancer, and in Phase II for Duschenne's muscular dystrophy (Leask, 2019, 2020; Richeldi et al, 2020). Collectively, targeting CCN2 with FG‐3019 may be an effect way to reverse established fibrosis and it will be used in clinical treatment of fibrotic diseases in the near future.…”