ProMetic’s PBI-4050 significantly reduces liver fibrosis in alström syndrome patients

This recommendation follows the DSMB’s review of the safety data accumulated in the first eight (8) Alström syndrome patients that had received treatment with PBI-4050. The DSMB determined that no safety or tolerability issues had been observed in these patients.

The early efficacy results in this phase 2, open-label study demonstrate that the first five (5) patients (100%) who completed 12 weeks of treatment with PBI-4050 had a significant reduction of liver fibrosis, as measured by transient elastography (FibroScan).

This reduction was also sustained for the first patient, who continued to show reduced fibrosis after having completed 24 weeks of treatment. The initial efficacy results also demonstrate that those patients with the most elevated liver enzymes at baseline (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline phosphatase) [ALP], had a significant reduction in all of these enzymes, to within normal ranges, after completing 4, 8 and 12 weeks of treatment with PBI-4050.

Queen Elizabeth Hospital Department of Endocrinology and Metabolism clinical trial principal investigator Dr. Tarekegn Geberhiwot said: “PBI-4050 has shown encouraging findings in patients with Alström Syndrome, being well tolerated and safe for up to 24 weeks. There have been beneficial effects observed in glycaemic control and early potential anti-fibrotic effects on the liver. 

"The rapidity of the effect is remarkable, with a reduction in the elevated levels of liver enzymes apparent within the first 4 weeks, and significant reductions in FibroScan scores within only 12 weeks in patients with established severe fibrosis”

ProMetic chief medical officer Dr John Moran said: “To me, patients with Alström syndrome display the most extreme features of Type 2 diabetes and liver fibrosis and a trial of PBI-4050 in this population is as challenging a test of the efficacy of PBI-4050 as I can imagine.

“The progression of liver fibrosis is much more aggressive in patients with Alström syndrome than in “typical” metabolic syndrome patients with obesity, diabetes and fatty liver, and so the major improvement in FibroScan score in all 5 patients in only 12 weeks is way beyond our expectations.  

Non-alcoholic fatty liver disease (“NAFLD”) is the manifestation of metabolic syndrome in the liver. Due to the worldwide obesity epidemic, NAFLD now affects 20–30% of the general population and thus has become by far the most common cause of chronic liver disease and we firmly believe that PBI-4050 will also be effective in that population."

The ongoing Alström syndrome phase 2 clinical trial is an open label, single arm and single center study investigating the safety, tolerability and efficacy of ProMetic’s small molecule lead compound PBI-4050 in a total of 20 patients.

The trial is being performed at the specialty center for the care of UK patients with Alström syndrome at the Queen Elizabeth Hospital, Birmingham, UK.

This center has recently published data showing that many of these patients show evidence of non-alcoholic fatty liver disease and advanced liver fibrosis at an early age, confirming previous publications showing a very high incidence of progression of NAFLD into liver cirrhosis with associated mortality in Alström patients.

ProMetic president and CEO Pierre Laurin said: “We are absolutely thrilled to see the beneficial effects that PBI-4050 has in patients with Alstr?m syndrome.

“These early results have motivated us to expand our program to Alström patients elsewhere in Europe and in North America. Furthermore, these results provide us with valuable clinical information as ProMetic pursues other unmet medical conditions where fibrosis plays a key role."