Early Data Support Oral Anti-Fibrotic Treatment, PBI-4050, for Pulmonary Hypertension

ProMetic Life Sciences recently presented positive preclinical data on its fibrosis-targeting lead candidate, PBI-4050, showing that the drug effectively reduces pulmonary hypertension and right ventricular hypertrophy. The company also presented positive effects of PBI-4050 on cardiovascular biomarkers in patients with metabolic syndrome and type 2 diabetes.

The data were presented at the American Heart Association’s (AHA) Scientific Sessions, held this month in New Orleans.

The preclinical study was led by Jocelyn Dupuis, MD, PhD, professor at the Department of Medicine, Université de Montréal, and a leader in PH with the Montreal Heart Institute. The researchers, working in a mouse model, investigated the benefits of PBI-4050 on cardiac and lung fibrosis, respiratory function, and lung remodeling following a myocardial infarction induced by coronary artery ligation. Two weeks after the heart attack, the animals were treated with PBI-4050 for three weeks.

“PBI-4050 effectively reduced pulmonary hypertension and right ventricular hypertrophy by reducing lung fibrosis and lung remodeling,” Dupuis said of the study’s findings in a press release. “These results strongly suggest that PBI-4050 has the potential to effectively treat the lung remodeling process in patients with Group 2 pulmonary hypertension and improve the right ventricular function. Moreover, PBI-4050 did not adversely affect the healing of the left ventricle and, in fact, we observed some improvement in left ventricular function.”

Left heart disease (LHD) represents the most common cause of pulmonary hypertension (PH – Group 2), and there are currently no approved therapies. Whether caused by systolic or diastolic dysfunction or valvular heart disease, a hallmark of PH associated with LHD is elevated left atrial pressure. In all cases, the increase in left atrial pressure causes a passive increase in pulmonary pressure. The condition commonly follows myocardial infarction, and often leads to lung remodeling characterized by myofibroblast proliferation and fibrosis.

PH that develops following a heart attack is associated with significantly worse clinical outcomes.

ProMetic reported in October that treatment with PBI-4050 significantly decreased biomarkers associated with a high risk of cardiovascular events. The data, from a preliminary analysis of new pro-inflammatory biomarkers in blood and urine samples of patients with metabolic syndrome and type 2 diabetes enrolled in the ongoing, open label, Phase 2 study (NCT02562573), provided additional evidence of PBI-4050’s pharmacological and clinical activity.

“The data from this [preclinical] study and several other experiments performed at the Montreal Heart Institute, along with the positive effects of PBI-4050 on several cardiovascular biomarkers in patients with Metabolic Syndrome, convince me that PBI-4050 may greatly benefit patients suffering from this form of pulmonary hypertension,” said Dr. John Moran, chief medical officer of ProMetic.

PBI-4050 is an oral drug designed to treat fibrosis, a process characterized by the replacement of normal tissue by fibrotic scar tissue, that can affect organs such as the lungs, heart, kidneys, and liver. PBI-4050 has been shown to be safe, well-tolerated, and to significantly reduce lung tissue scarring in animal models.

PBI-4050 (800 mg daily) is also being evaluated in an open-label Phase 2 clinical trial (NCT02538536) in 40 patients with idiopathic pulmonary fibrosis (IPF). The ongoing study, taking place in Canada, is evaluating the treatment’s safety, tolerability, and efficacy on lung function, disease progression, and fibrotic/inflammatory biomarkers.