Metabasis and Daiichi Sankyo issued negative results from a phase IIb trial of CS-917 for the treatment of type II diabetes. This multi-center, double-blind, placebo-controlled trial enrolled 392 subjects who were divided into four treatment arms to receive CS-917 at 50 mg BID or 100 mg BID, metformin at 850 mg BID or placebo, for three months.
Both doses of CS-917 failed to meet the primary endpoint of significantly lowering the placebo-adjusted level of glycosylated hemoglobin (HbA1c), a measure of glucose load.
The mean HbA1c level at the start of the study was approximately 7.6-7.7%. The placebo adjusted HbA1c level at the end of treatment was unchanged at the CS-917 low dose and there was a 0.17% decrease at the high dose (p=0.1256). Metformin treatment resulted in a placebo-adjusted decrease of HbA1c of 0.50% (p less than 0.0001).
Metabasis and Daiichi Sankyo plan to fully evaluate the data to determine a future course of action. CS-917 is being being developed by Daiichi Sankyo through a licensing agreement between Metabasis and Daiichi Sankyo.
In a statement by, Dr. Mark Erion, executive vice president of research and development and chief scientific officer at Metabasis Therapeutics said:
"We are surprised and disappointed by the results we have seen so far in this important Phase 2b clinical trial, especially after the promising preclinical and early clinical results from smaller 14-day and 28-day studies."
The company stated their were many unanswered questions raised by the trial.
"For example, the fasting plasma glucose levels and HbA1c levels in patients at the start of the Phase 2b trial were substantially lower than were studied in the previous Phase 2a clinical trials. We want to explore if this could have impacted the results. This is but one of many factors we plan to evaluate. We expect to work closely with Daiichi Sankyo over the coming weeks to analyze and compare the outcomes of this and previous trials. These efforts may help the Metabasis team to determine the impact of these findings on CS-917 and the gluconeogenesis inhibitor class of drug candidates, including MB07803," said Erion.