PBI-4050 Data Suggest Reversal of Liver and Heart Fibrosis in Alstrom Patients

Clinical data from an ongoing Phase 2 study of PBI-4050 shows that the drug provides a clear clinical benefit in patients with Alstrom syndrome.

In September, the company released FibroScan data from 8 patients for 36 weeks or more, in addition to data from liver enzymes and biomarkers. The more recent news highlights FibroScan data from 10 patients, and confirms the previous results with a liver MRI. Most importantly, though, it shows heart MRI data, which has never been released.

Alström syndrome, a severe model of fibrosis, is an ultra-rare genetic disorder characterized by severe multi-organ fibrosis and has no currently approved treatments.

The trial examined the clinical benefits in 12 patients treated with PBI-4050 for varying lengths of time with an average of 52 weeks. It was reported that clinical activity and tolerability of the drug are sustained with prolonged treatment, and further clinical activity in the heart and liver was observed with longer treatment exposure.

Earlier this year, the developer of the drug, Prometic Life Sciences, Inc., published an article in the American Journal of Pathology detailing PBI-4050’s 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.

"Progressive cardiac fibrosis is the most serious feature of Alström syndrome, and the resultant heart failure is the most common cause of death," said Dr. John Moran, Chief Medical Officer of Prometic in a press release.

"Therefore, the results observed with the cardiac MRI are very promising and exceeded our expectations. Going into the study, we had been hoping to see a slowing of the rate of progression, but in fact, we have observed a regression in cardiac fibrosis. Additionally, the liver MRI further supports the FibroScan scores and the reduction of fibrosis observed in these patients. Importantly, PBI-4050's clinical activity and tolerability have been confirmed over this extended period, with no drug-related serious adverse events. The clinical activity observed in these patients gives us further confidence in the forthcoming pivotal Phase 3 clinical trial in patients with idiopathic pulmonary fibrosis."

An analysis of the interim cardiac MRI data indicates a reduction of cardiac fibrosis in each patient after initiation of treatment with PBI-4050 (p<0.001). Fibroscan results from the 10 subjects who received at least 36 weeks of treatment exhibited a statistically significant improvement in the measure of liver stiffness. A reduction of liver fibrosis observed in patients was evidenced by a FibroScan score that was reduced or stabilized in 9 out of 10 patients treated for 36 weeks or more.

Prometic intends to work closely with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to define PBI-4050’s clinical-regulatory pathway in Alström syndrome. Pierre Laurin, President and Chief Executive Officer of Prometic, stated: “We are scheduled to meet this summer with the European and the U.S. regulatory authorities to determine the clinical-regulatory pathway for this investigational treatment for patients with Alström, who are in serious need of an anti-fibrotic treatment. This is a critical step to determine whether this ultra-rare pediatric disorder could be an indication granted priority review.”

No drug-related serious adverse events (AEs) were observed in the Phase 2.

In addition to ongoing studies of PBI-4050 being conducted in Alström syndrome, Prometic is also doing research on its drug in idiopathic pulmonary fibrosis (IPF). Prometic intends to initiate pivotal Phase 3 clinical trials in patients with IPF to evaluate PBI-4050 as both a standalone treatment and as a supplement to nintedanib (Ofev).

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