IPF is a chronic disease characterized by a progressive decline in lung function, because the lung’s small air sacs are being replaced with scar tissue, causing shortness of breath. The disease usually affects people between the ages 50 to 70, and the prognosis is poor. Men and women with a smoking history are more likely to develop the disease.
How PBI-4050 works
PBI-4050 is designed to regulate inflammation and fibrosis (or scarring). The drug works by reducing the level of pro-fibrotic cytokines (chemical signals that promote scarring), fibrocyte differentiation, and microfibroblast activation, to improve organ function.
Animal studies showed thatPBI-4050 is able to successfully reduce the amount of proteins involved in inflammation and fibrosis. These include:
- Transforming growth factor 1 beta (TGF- 1b ), which is responsible for cell growth, differentiation, and maturation
- Connective Tissue Growth Factor (CTGF), which is responsible for helping TGF- 1b sustain fibrosis and increase extracellular matrix production
- Members of the interleukin family, such as IL-23p19 and IL-6, which are pro-inflammatory in nature.
The results of preclinical studies showed that PBI-4050 significantly reduced lung tissue scarring in animal models.
A Phase 1 study that enrolled 40 healthy volunteers showed that PBI-4050 was safe and well-tolerated with no adverse events being reported.
A Phase 2 (NCT02538536) open-label, single-arm, and exploratory trial of PBI-4050, at 800 mg daily, was started in July 2015 and completed in January 2017. The trial, which enrolled 40 IPF patients at six Canadian sites, tested the safety, tolerability, and efficacy of the drug in terms of lung function and disease progression. During the treatment period, which lasted 12 weeks, nine participants received PBI-4050 alone, 16 received PBI-4050 and Ofev (nintedanib), and 15 received PBI-4050 and Esbriet (pirfenidone). The baseline characteristics of the enrolled participants were similar to those enrolled in previous Phase 3 studies (ASCEND and IMPULSIS-1 and IMPULSIS-2) of other drugs, including Esbriet.
Data from this study were presented at the 2017 American Thoracic Society (ATS) International Conference. PBI-4050 was found to be safe and well-tolerated when given alone or in combination with Ofev or Esbriet. Participants receiving either PBI-4050 alone or in combination with Ofev showed a lesser decline in forced vital capacity (FVC, a measure of lung function) than patients treated with a placebo. However, PBI-4050 levels were reduced in combination with Esbriet, suggesting a possible poor drug-drug interaction. The company also presented data that shows that PBI-4050 has an effect on the regulation of biomarkers involved in human lung fibrosis.
Prometic plans to start two Phase 2/3 placebo-controlled study, the first for IPF patients who failed to tolerate Ofev or Esbriet, in which participants will be randomized to either receive PBI-4050 as monotherapy or receive a placebo, and the other in which the combination of PBI-4050 and Ofev will be tested. Both studies are expected to start in the second half of 2017.
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