Pamrevlumab: A Promising Candidate with Groundbreaking Potential in Idiopathic Pulmonary Fibrosis Space

Connective tissue growth factor (CTGF), is a critical mediator in the progression of fibrosis and related serious diseases. FibroGen is developing Pamrevlumab, a fully-human monoclonal antibody that inhibits the activity of CTGF and in turn can benefit in Idiopathic Pulmonary Fibrosis (IPF) along with Pancreatic Cancer, and Duchenne Muscular Dystrophy

FibroGen recently announced positive top line data for Pamrevlumab from phase 2 randomized, double-blind, placebo-controlled study and two combination safety sub-studies of Pamrevlumab in patients with idiopathic pulmonary fibrosis (IPF)

PharmGPS^® distinguished Pamrevlumab from other emerging drugs months in advance, based on initial Phase II data regarding its efficacy, safety and dosing regimen, as one of the front runners for treating patients with IPF. Pamrevlumab, using PharmGPS^® proprietary algorithm, was anticipated to emerge as one of the top clinical assets in IPF space. With comparable safety profile to approved therapies and better efficacy than molecules in clinical development, it outperformed around 16 other molecules in the similar phase.

Pamrevlumab is expected to represent a significant landmark for IPF patient community, as is evident from its excellent clinical data in Phase II

PharmGPS^® analysis revealed advantages of targeting CTGF in IPF. As in IPF, CTGF is a key mediator in the progression of fibrosis. It is induced by transforming growth factor beta (TGFbeta) and it is also hypothesized to act as a mediator of some profibrotic effects of TGFbeta. There are substantial evidences around the profibrotic effect of CTGF and its contribution to lung fibrosis through transcriptional activation of Col1a2. Blocking strategies has revealed the signaling mechanisms involved. These findings show CTGF to be a rational target for therapy in fibrotic diseases such as IPF

Currently, ProMetic Life Sciences (PBI-4050), in addition to FibroGen (Pamrevlumab), is also developing CTGF inhibitor for the treatment of IPF. Although both the candidates are almost equally efficacious and safe, PBI-4050 will enjoy the benefit of being in oral form. However, FibroGen achieved a significant advantage in trial confidence by testing the drug in more number of patients and backed with the recent clinical data, Pamrevlumab is likely to outperform PBI-4050.

The clinical trial results published for Pamrevlumab and PBI-4050 to date are summarized below:

PharmGPS^® analyzed the performance of both the drugs as closely comparable on efficacy and safety fronts. However, scenario may change when these candidates will be tested in larger population in phase III trials

PharmGPS^® has done a comprehensive evaluation of IPF pipeline. There are more than 36 molecules in clinical development for IPF with only one molecule in PIII development i.e. recombinant human thrombomodulin alpha (ART-123). However, there are number of molecules in lower clinical phases (17 PI assets and 18 PII assets). Among phase II candidates, PRM-151 (Promedior Inc) and GLPG1690 (Galapagos NV) have also shown potential in IPF. Rest of the pipeline is still immature as trials for most of the molecules are ongoing, or results are not available for analysis

About IPF:

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia. It is estimated to affect 20 persons per 100,000 for males and 13 persons per 100,000 for females globally. In the US, prevalence (age-adjusted and sex-adjusted) among residents aged 50 years or older ranges from 27.9 cases per 100,000 persons to 63 cases per 100,000 persons

There is a significant unmet medical need in this space as IPF portends a poor prognosis, with an estimated mean survival of 2-5 years from the time of diagnosis. Estimated mortality rates are 64.3 deaths per million in men and 58.4 deaths per million in women