Positive phase 3 trial results for potential first-in-class oral diabetes drug

Top-line results from the TIMES 3 study demonstrate the experimental oral diabetes drug imeglimin achieved its primary safety and efficacy endpoints, according to a press release from Poxel and Sumitomo Dainippon Pharma Co.

Imeglimin is an oxidative phosphorylation blocker that inhibits hepatic gluconeogenesis, increases muscle glucose uptake and restores normal insulin secretion. The agent will be a first-in-class diabetes therapy, if approved. The TIMES 3 study was a 16-week, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of imeglimin in 215 Japanese patients with inadequately controlled type 2 diabetes using insulin.

“For patients with type 2 diabetes who are inadequately controlled on insulin alone, TIMES 3 data show that imeglimin has the potential to be a new treatment option that could significantly reduce HbA1c with a favorable safety and tolerability profile,” Christophe Arbet-Engels, MD, PhD, chief medical officer and executive vice president of late development and medical affairs at Poxel, said in the release. “The TIMES 3 16-week results are the second positive readout from the three pivotal trials in the TIMES program and follow the positive TIMES 1 monotherapy results announced in April 2019. We are working very closely with our partner Sumitomo Dainippon Pharma in preparing for the Japanese new drug application, and these results bring us one step closer to achieving that goal.”

In TIMES 3, researchers randomly assigned patients to 1,000 mg imeglimin twice daily in combination with insulin or placebo plus insulin. The trial demonstrated efficacy and achieved statistical significance (P < .0001) for its primary endpoint, defined as a change in HbA1c from baseline vs. placebo at week 16, with a mean HbA1c placebo-corrected change from baseline of –0.6%, according to the release.

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Top-line results from the TIMES 3 study demonstrate the experimental oral diabetes drug imeglimin achieved its primary safety and efficacy endpoints.
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In this trial, the overall safety and tolerability of imeglimin was similar to placebo. There were no between-group differences for hypoglycemia and no severe hypoglycemia events documented. The adverse event profile was similar to placebo and consistent with what was observed in the TIMES 1 monotherapy trial and other imeglimin clinical trials.

The companies stated that additional analyses of the trial, including secondary endpoints, are ongoing and the results of the 36-week open-label extension part of TIMES 3 are anticipated at the end of this year.

As Endocrine Today reported in 2017, phase 2b data presented at the at the European Association for the Study of Diabetes Annual Meeting demonstrated that imeglimin was found to be safe and effective in Japanese adults, with patients experiencing a significant reduction in HbA1c at all doses. The reduction was dose dependent, with a 0.52% reduction for 500 mg, 0.94% reduction for 1,000 mg and 1% for 1,500 mg. At doses of 1,000 mg and 1,500 mg, there was a significant reduction in fasting plasma glucose, glycated albumin and percentage of patients reaching HbA1c below 7%, the researchers said.

The TIMES program is a joint development effort between Poxel and Sumitomo Dainippon Pharma. The companies entered into a strategic partnership in October 2017 for the development and commercialization of imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast and East Asian countries.

Poxel anticipates presenting full data results from the phase 3 TIMES 3 16-week portion of the trial at an upcoming scientific meeting. – by Regina Schaffer

Top-line results from the TIMES 3 study demonstrate the experimental oral diabetes drug imeglimin achieved its primary safety and efficacy endpoints, according to a press release from Poxel and Sumitomo Dainippon Pharma Co.

Imeglimin is an oxidative phosphorylation blocker that inhibits hepatic gluconeogenesis, increases muscle glucose uptake and restores normal insulin secretion. The agent will be a first-in-class diabetes therapy, if approved. The TIMES 3 study was a 16-week, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of imeglimin in 215 Japanese patients with inadequately controlled type 2 diabetes using insulin.

“For patients with type 2 diabetes who are inadequately controlled on insulin alone, TIMES 3 data show that imeglimin has the potential to be a new treatment option that could significantly reduce HbA1c with a favorable safety and tolerability profile,” Christophe Arbet-Engels, MD, PhD, chief medical officer and executive vice president of late development and medical affairs at Poxel, said in the release. “The TIMES 3 16-week results are the second positive readout from the three pivotal trials in the TIMES program and follow the positive TIMES 1 monotherapy results announced in April 2019. We are working very closely with our partner Sumitomo Dainippon Pharma in preparing for the Japanese new drug application, and these results bring us one step closer to achieving that goal.”

In TIMES 3, researchers randomly assigned patients to 1,000 mg imeglimin twice daily in combination with insulin or placebo plus insulin. The trial demonstrated efficacy and achieved statistical significance (P < .0001) for its primary endpoint, defined as a change in HbA1c from baseline vs. placebo at week 16, with a mean HbA1c placebo-corrected change from baseline of –0.6%, according to the release.

#
Top-line results from the TIMES 3 study demonstrate the experimental oral diabetes drug imeglimin achieved its primary safety and efficacy endpoints.
Shutterstock

In this trial, the overall safety and tolerability of imeglimin was similar to placebo. There were no between-group differences for hypoglycemia and no severe hypoglycemia events documented. The adverse event profile was similar to placebo and consistent with what was observed in the TIMES 1 monotherapy trial and other imeglimin clinical trials.

The companies stated that additional analyses of the trial, including secondary endpoints, are ongoing and the results of the 36-week open-label extension part of TIMES 3 are anticipated at the end of this year.

As Endocrine Today reported in 2017, phase 2b data presented at the at the European Association for the Study of Diabetes Annual Meeting demonstrated that imeglimin was found to be safe and effective in Japanese adults, with patients experiencing a significant reduction in HbA1c at all doses. The reduction was dose dependent, with a 0.52% reduction for 500 mg, 0.94% reduction for 1,000 mg and 1% for 1,500 mg. At doses of 1,000 mg and 1,500 mg, there was a significant reduction in fasting plasma glucose, glycated albumin and percentage of patients reaching HbA1c below 7%, the researchers said.

The TIMES program is a joint development effort between Poxel and Sumitomo Dainippon Pharma. The companies entered into a strategic partnership in October 2017 for the development and commercialization of imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast and East Asian countries.

Poxel anticipates presenting full data results from the phase 3 TIMES 3 16-week portion of the trial at an upcoming scientific meeting. – by Regina Schaffer