Betagenon/Baltic Bio announces positive results from a 28 day Phase IIa trial of the first-in-class AMPK activator.
The main study results are not yet finalized but review of the initial data showed that a number of patients who were included based on HbA1c at screening, had FPG below 7 mM or above 13.3 mM at day 1, and that the data analysis of FPG required a post hoc analysis plan, according to the company. In type 2 diabetic patients on Metformin with FPG >7 mM and <13.3 mM (>126 and <240 mg/dl) at day 1, where FPG >13.3mM defines uncontrolled hyperglycemia, there were statistical significant differences between the treatment groups in the absolute and relative change in FPG at day 28. The mean absolute reduction in the Placebo group (n=24) was -0.10 mM and for the O304 group (n=25) -0.60 mM with a p-value of 0.0096. The p-value for the relative change was 0.0178. Within the treatment groups O304, but not Placebo, caused a significant absolute (p=0.0002) and relative (p=0.0003) reduction in FPG at day 28 compared to day 1. Within the treatment groups O304, but not Placebo, caused a significant absolute reduction in HOMA-IR (p=0.0097), however, the comparison to Placebo did not reach statistical significance. At day 40, 12 days after end of treatment, compared to day 28 there was a statistically significant difference between the groups with an absolute increase in FPG, and a relative increase in HOMA-IR in the O304 group.
Within the treatment groups of type 2 diabetic patients who completed examination by magnetic resonance imaging at screening and at day 28 and irrespective of FPG at baseline, O304, but not Placebo, showed a statistically significant absolute and relative reduction in diastolic blood pressure and a relative reduction in systolic blood pressure. O304, but not Placebo, also caused a statistically significant absolute and relative increase in level of peripheral microvascular perfusion, and a relative increase in the rate of perfusion.
The composite endpoint is defined as a decrease in blood pressure and increase in vascular perfusion in order to be a success, all other outcomes is classified as failures. This composite endpoint showed statistically significant difference between the treatments with more successes in the O304 group, i.e. more patients had both a decrease in blood pressure and an increase in vascular perfusion.
During the Phase IIa trial no safety signals were observed and O304 was well tolerated.
“We are very pleased that the beneficial metabolic and vascular effects observed with O304 in animal disease models translated to type 2 diabetic patients in the 28 day Phase IIa trial, providing strong support for further clinical development according to plan of first-in-class AMPK activator O304 in type 2 diabetes,” said Thomas Edlund, CEO Betagenon.