Earlier this month, the American Journal of Pathology
, the official journal of the American Society of Investigational Pathology, published a paper detailing the activity of the mechanism of action in PBI-4050 in idiopathic pulmonary fibrosis (IPF).
PBI-4050, being developed by Prometic Life Sciences, Inc., is a small molecule lead drug candidate that contains a novel antifibrotic mechanism of action. The paper, titled “A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84
,” documents the discovery of an antifibrotic pathway involving the pair of title receptors.
The company received orphan drug designation
from the U.S. Food and Drug Administration (FDA) for PBI-4050 in the IPF indication in February 2015.
Lyne Gagnon, primary author of the paper and Prometic’s Vice-President of R&D Pre-clinical, and her team of researchers examined PBI-4050’s ligand affinity in vitro
and in vivo
for the fatty acid receptors, GPR40 and GPR84, both of which are known to be involved in diverse physiological processes related to metabolic regulation and to inflammation. Prior to this study, the fundamental importance of these receptors in the fibrosis pathways had not been recognized, and the authors were the first to discover a novel antifibrotic pathway involving both receptors.
“In studying the mechanism of action of PBI-4050, we have clearly demonstrated the contribution of two fatty acid receptors, GPR40 and GPR84, in the regulation of cells involved in fibrosis, including macrophages, epithelial cells and fibroblasts,” said Dr. Gagnon.
The implications of these discoveries could have great impact on the IPF community, as any drug that can stimulate the positive receptor while inhibiting the negative receptor could potentially delay, prevent or even reverse progression of disease.
“We have seen the benefits of PBI-4050 in the treatment of fibrotic diseases,” said Pierre Laurin, Chief Executive Officer of Prometic. “Now, having an understanding of the unique mechanism of action of PBI-4050, we are more confident than ever in its potential to help patients suffering from fibrosis-related conditions such as IPF and Alström Syndrome. We look forward to initiating our Phase 3 pivotal clinical trial for PBI-4050 in IPF, expanding the program in Alström Syndrome and to advancing follow-on analogues of PBI-4050 in clinical programs targeting other large fibrosis-related unmet medical needs.”
With this data, and following the confirmation of the trial design in a recent clinical development Type C meeting with the FDA, Prometic intends to initiate pivotal Phase 3 clinical trials of PBI-4050 in patients with IPF.
The Phase 3 trial will evaluate PBI-4050 both as a standalone treatment and as a supplement to nintedanib (Ofev), and is expected to begin patient enrollment in mid-2018.
Per the National Institutes of Health
(NIH), IPF typically presents in adults between their fifth to seventh decade of life, and is more prevalent in those with a history of cigarette smoking. IPF affects men more often than women, and approximately 130,000 total people in the United States. There are an estimated 48,000 new cases diagnosed annually, and almost 40,000 people with IPF die each year.
For more information on studies pertaining to the rare disease community, follow Rare Disease Report
. To get breaking rare disease news sent straight to your inbox, subscribe RDR