Poxel’s Diabetes Drug Wins Japan Nod, However Competitors Stays Fierce

As the French biotech company Poxel marks the first approval of its oral type 2 diabetes drug in Japan, the future of this drug and its competitors in Europe and the United States is turning its attention.

The fortunes of Lyon-based company Poxel were strengthened with the first ever regulatory approval of its oral type 2 diabetes drug imeglimin hydrochloride, marketed in Japan as Twymeeg. Elsewhere, however, the future of the drug remains less clear.

Imeglimin’s approval was based on three Phase III studies in which the drug helped patients control their blood sugar levels. The nod sparked a € 13.3 million milestone payment from Poxel’s Japanese partner company Sumitomo Dainippon Pharma in a more than € 213 million deal that will include revenue-based payments and escalating double-digit royalties following the drug’s expected launch in October.

The good news comes after the company suffered a bruise late last year when its US and European partner Roivant pulled out of a license and development agreement for the drug after a strategic review. The rights were subsequently returned to Poxel in January, and according to its annual report last month, the company has no plans to advance the drug in those regions on its own.

At the time of Roivant’s exit, Poxel stressed that the larger partner’s decision was not based on efficacy, safety or other data from Imeglimin. Phase II development had already been completed, and at a meeting with the US Food and Drug Administration (FDA) last year, Roivant had positive evidence that the drug could be used in patients with type 2 diabetes and moderately to severely chronic patients Kidney Disease (CKD) – two conditions that often overlap.

It is possible, however, that Roivant and its subsidiary Metavant have been unwilling to organize and fund massive Phase III trials that are often required in developing treatments for common, competitive indications such as type 2 diabetes. This limits the number of advanced biotech and pharmaceutical companies in the diabetes space to those with the deepest pockets.

Poxel CEO and co-founder Thomas Kuhn remains confident that the drug will play a unique role in the treatment of type 2 diabetes. Imeglimin is designed to prevent damage to energy-producing mitochondria in tissues related to diabetes including the liver and pancreas.

“We believe that imeglimin is the only oral compound with a dual mechanism of action specifically designed to both increase insulin secretion in response to glucose and reduce insulin resistance,” he told me.

“Because of these effects, we believe that imeglimin has the potential to slow disease progression and offer therapeutic options to patients who are unresponsive to current treatments.”

Although Poxel did not experience any immediate financial consequences from withdrawing from Roivant last year, the company admits it will miss out on up to 506 million euros expected under the deal.

Imeglimin could also face increasingly tougher competition as drugs are approved by competitors and come onto the market, especially for patients with type 2 diabetes and CKD. A big competitor is AstraZeneca’s Farxiga, which blocks a protein called SGLT2. Farxiga received FDA approval for the treatment of CKD with or without type 2 diabetes in April, and EU approval is likely to follow shortly.

Drugs mimicking a hormone called glucagon-like peptide 1 have dominated the type 2 diabetes market for some time, but were not available as an oral formulation until the EU approval of Novo Nordisk’s semaglutide in 2020. With both cardiovascular and weight loss benefits associated with this drug, it is likely to be a strong competitor for imeglimin.

New candidates are also in the pipeline, such as the next-generation synthetic omega-3 fatty acid epeleuton from Irish biotech Afimmune. The Phase II drug is a derivative of an eicosapentaenoic acid (EPA) metabolite, said the company’s executive medical director, Moayed Hamza. He found that EPA, marketed as icosapentethyl by Dublin-based Amarin, significantly reduced cardiovascular risk.

“There have been significant developments in the treatment of type 2 diabetes over the past decade, with an increasing focus on cardiovascular and renal outcomes,” Hamza told me.

“We believe that new treatments for type 2 diabetes must improve cardiovascular or renal outcomes to be effectively competitive, especially in the US and Europe.”

Poxel claims he is not aware of any other advanced competitors who behave in the same way as Imeglimin. By targeting the mitochondria directly, the drug can fight high blood sugar levels in various organs at the same time by restoring insulin secretion in the pancreas, increasing glucose uptake by muscles, and reducing the amount of excess glucose produced by the liver .

Kuhn points out that the Japanese market is of special importance as the world’s second largest diabetes market outside of the United States, with more than 10 million people living with the disease and an average annual growth rate of 20%. The Japanese authorities also place great emphasis on the treatment and prevention of age-related diseases such as diabetes as the population ages rapidly.

Poxel was able to rapidly advance Imeglimin with Sumitomo Dainippon Pharma, also thanks to the close cooperation with the Japanese drug and medical device authority.

“This resulted in a successful Phase III development program with over 1,000 patients that lasted only two years, followed by the JNDA [Japanese New Drug Application] Submission and approval, ”he said.

Cover picture by Anastasiia Slynko