The French metabolic experts at Poxel and their Asian partners at Sumitomo Dainippon Pharma have hit a home run with the first late-stage Japanese test of their oral diabetes drug imeglimin, which bodes well for the pair of Phase III trials expected to readout later this year and fuels the blockbuster expectations tagged on the mitochondrial therapy.
The drug belongs to a new chemical class of oral agents called ‘glimins’ that simultaneously target all three key organs involved in diabetes: the pancreas, the liver and the muscles. Imeglimin is designed to work on the two main defects seen in patients with type II diabetes: by increasing insulin secretion in the pancreas, in a glucose-dependent manner; and by decreasing the excess production of glucose by the liver, while enhancing ‘insulin sensitivity’ in the muscles.
The TIMES 1 trial tested a 1000 mg dose of imeglimin against a placebo in 213 Japanese patients with type 2 diabetes. The drug induced a statistically significant reduction (p<0.0001) in HbA1c — average blood sugar levels over a period of weeks/months — at week 24, meeting the main goal. The placebo-corrected mean change in HbA1c from baseline was – 0.87%, the companies said.
The drug also met the main secondary goal of reducing fasting plasma glucose, and analyses of other secondary endpoints are ongoing.
With an aging population and growing rates of obesity, diabetes in Japan has ballooned, with the number of suspected diabetics hitting a record 10 million for the first time in 2016, according to government estimates cited by Nikkei.
“The TIMES 1 results confirm the robust efficacy combined with favorable safety observed in the Phase 2b trial in Japan and the potential benefits that Imeglimin can bring to type 2 diabetes patients globally,” said Poxel chief Thomas Kuhn. “The TIMES 1 data is the first major step towards filing the Japanese New Drug Application in 2020. Japan represents the second largest single market for type 2 diabetes and, Asia, in broader terms, is considered the most important geographic location with regards to treating the diabetes pandemic in the future.
In 2016, Poxel reported that a Phase IIb trial in Japan registered hemoglobin A1c reductions of 0.52%, 0.94% and 1.00% for the 500 mg, 1000 mg and 1500 mg dose twice-daily. In 2017, the Merck Serono spinout forked over the Asia rights to the treatment to Sumitomo Dainippon Pharma in a deal worth up to $300 million.
Data from TIMES-2 and TIMES-3 are expected later this year. Poxel (EPA: $POXEL) out-licensed the rights to imeglimin in the United States and Europe to Vivek Ramaswamy’s Roivant Sciences last year, with this partner funding the majority of the costly Phase III programme expected to commence this year.
“Imeglimin has a novel mechanism of action as a mitochondrial bioenergetics enhancer, potentially providing a unique position in the competitive type II diabetes treatment landscape,” Jefferies analysts wrote in a note last month. They modeled a 60% probability of commercial success for imeglimin in the US/EU and Asia, with an estimate of $3.1 billion in global peak sales, including $600 million in Japan.
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