Roivant-backed Merck Serono spinout hits phase 3 diabetes goal; NDA on the horizon

There are a lot of oral Type 2 diabetes medicines on the market and in development, so any update about a new drug is usually lost or downgraded in interest to other areas like cancer or rare diseases.

Poxel, a biotech spun out of Germany’s Merck and based in France, and Japanese partner Sumitomo Dainippon Pharma are doing things a little differently, however, after announcing positive data from their late-stage diabetes study in Japan.

The pair has been studying imeglimin, a new type of drug which the partners say is the first clinical candidate in a new chemical class of oral agents called Glimins, which targets mitochondrial bioenergetics.

The drug works as an oral oxidative phosphorylation blocker, with midstage data showing its drug increases insulin secretion while cutting excess glucose production. Current marketed drugs include GLP-1 agonists and DPP-4 inhibitors as well as older generics such as sulfonylureas.

Phase 2b data out last year saw investigators in Japan enroll 299 patients and randomize them to receive one of three doses of imeglimin or placebo. Patients got treatment twice a day for 24 weeks. The primary endpoint looked at glycated hemoglobin A1c, a type of hemoglobin that shows the three-month average plasma glucose concentration. A secondary efficacy endpoint looked at levels of fasting plasma glucose.

All three doses of imeglimin outperformed placebo in terms of reducing levels of the hemoglobin. The response was dose dependent. Subjects who received the lowest, 500 mg dose experienced a reduction of 0.52%. Participants who took the highest, 1500 mg dose experienced a reduction of 1.00%. The declines are larger than those seen in earlier trials in the U.S. and Europe.

Today, it posted results out of its phase 3 TIMES 1 test, pitting a 1,000 mg version of imeglimin twice-daily against a dummy therapy placebo for 24 weeks in 213 Japanese patients. The TIMES 1 trial “demonstrated robust efficacy and achieved statistical significance (p<0.0001) for its primary endpoint, defined as a change of glycated hemoglobin A1c (HbA1c) versus placebo at week 24, with an HbA1c placebo-corrected mean change from baseline of -0.87%,” the partners said in a release.

For the trial’s main secondary endpoint, of a decrease from baseline in fasting plasma glucose (FPG), imeglimin also achieved statistical significance versus placebo at week 24, with a FPG placebo-corrected mean change from baseline of -19 mg/dL.

“Analyses of data for the additional secondary endpoints are ongoing,” the companies said, with safety “similar to placebo” and consistent with other data out from its earlier tests. More detailed data are slated to be published later this year.

Thomas Kuhn, CEO of Poxel, said: “This is a significant milestone for Poxel and for the development of our most advanced drug candidate. 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.

“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.”

RELATED: Roivant expands into metabolic diseases with $650M Poxel diabetes pact

Poxel had positive, initial phase 2 data as far back as 2014, but had a long wait for a partner to move this drug into the much more expensive rounds of later-stage testing.

It eventually teamed up with Sumitomo in 2017 for its Japanese work, and last year gained the attention of Vivek Ramaswamy’s biotech Roivant, penning a $650 million deal that saw it gain near-global rights to Poxel’s imeglimin.  

The well-resourced private biotech paid $35 million (€28 million) up front and took a $15 million, 6% stake in Poxel in return for the rights to imeglimin outside of Japan, China and some other Asian countries (where Poxel and its partner maintain rights). Roivant is also on the hook for up to $600 million in milestones.

Poxel pays $25 million toward clinical trials of imeglimin, but, crucially, Roivant takes on the heavy financial and developmental lifting that were beyond the capabilities of the French biotech. Roivant plans to move the drug into a U.S. and European phase 3 program this year, and today’s data from Japan will likely be a boon for those plans.

Poxel is also working on PXL770, a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, which just started a midstage, proof-of-concept test for NASH, alongside an earlier effort, PXL065 (deuterium-stabilized R-pioglitazone), a mitochondrial pyruvate carrier inhibitor, which is also targeting the fatty liver disease in a phase 1.

Poxel’s shares, traded in Europe, were up nearly 8% on the news in early trading this morning.