FDA approves Prometics PBI-4050 Clinical trial design

Prometic Life Sciences announced that it has received approval from FDA on the design of the first of its PBI-4050 planned phase 2/3 clinical trials for IPF based on the efficacy data generated in the recently completed 40 patient Phase 2 open-label study.

In that phase 2 study, PBI-4050 was given for 12 weeks to patients who were receiving pirfenidone, nintedanib, or neither agent. The results of the study showed that the Forced Vital Capacity (FVC) remained stable in patients on PBI-4050 alone (n=9, FVC -12 ml) or in patients on PBI-4050 in combination with nintedanib (n=15, FVC +2 ml). In contrast, the results showed that the FVC declined significantly in patients on PBI-4050 in combination with pirfenidone (n=16, FVC -105 ml). PBI-4050’s plasma concentration was sub-therapeutic at 50% of the expected level in patients that received the PBI-4050 and pirfenidone combination, suggesting a drug-drug interaction.

Prometic Chief Medical Officer, Dr. John Moran said that this early evidence of efficacy observed with PBI-4050 alone or in combination with nintedanib points toward very promising treatment options that will be further tested in two separate phase 2/3 clinical trials. they are very pleased that the FDA concurs with their decision to exclude a combined pirfenidone and PBI-4050 treatment arm in the upcoming phase 2/3 add-on study.

Prometic also intends to initiate a second phase 2/3 placebo-controlled trial which would enroll IPF patients who have failed to tolerate nintedanib or pirfenidone and would be randomized to receive either PBI-4050 or placebo.

Idiopathic Pulmonary Fibrosis (“IPF”)

IPF is a chronic, devastating, and ultimately fatal disease characterized by a progressive decline in lung function. It is a specific type of interstitial lung disease in which the small air sacs of the lung, the “alveoli,” gradually become replaced by fibrotic (scar) tissue and is the cause of worsening dyspnea (shortness of breath). IPF is usually associated with a poor prognosis. The term ‘idiopathic’ is used because the cause of pulmonary fibrosis is still unknown. IPF usually occurs in adult individuals of between 50 and 70 years of age, particularly those with a history of cigarette smoking, and affects men more often than women. IPF affects about 130,000 people in the United States, with about 48,000 new cases diagnosed annually. Approximately 40,000 people die each year with IPF, a similar number of deaths to those due to breast cancer. The 5-year mortality rate for subjects with IPF is estimated to range from 50% to 70%.

PBI-4050

PBI-4050 is an orally active lead drug candidate with excellent safety and efficacy profiles confirmed in several in vivo experiments targeting fibrosis. Fibrosis is a very complex process by which continuing inflammation causes vital organs to lose their function as normal tissue is replaced by fibrotic scar tissue. The proof of concept data generated to date confirms our lead drug candidates’ anti-fibrotic activity in several key organs including the kidneys, the heart, the lungs and the liver. Twenty six million subjects in the U.S. alone are believed to suffer from chronic kidney diseases (“CKD”). Subjects with severe CKD stages (3 and 4) suffer from a progressive loss of their renal function leading to end-stage renal disease and the need for dialysis or kidney transplant. Cardiovascular complications are the most common cause of death in dialysis subjects.