As French biotech Poxel marks the first market approval of its oral type 2 diabetes medication in Japan, eyes turn to the future of this drug and its rivals in Europe and the US.
The fortunes of the Lyon-based Poxel have been boosted by the first-ever regulatory approval of its oral type 2 diabetes medication imeglimin hydrochloride, which is marketed as Twymeeg in Japan. Elsewhere, however, the drug’s future remains less clear.
The approval of imeglimin was based on three phase III trials, where the drug helped patients to control their blood glucose. The nod triggered a €13.3M milestone payment from Poxel’s Japanese partner company Sumitomo Dainippon Pharma, in a €213M plus deal that will include sales-based payments and escalating double-digit royalties following the drug’s expected launch in October.
The good news comes after the company took a bruising late last year when its US and European partner Roivant pulled out of a licensing and development deal for the drug following a strategic review. Rights subsequently reverted to Poxel in January and, according to its annual report last month, the firm doesn’t plan to advance the drug in these regions on its own.
At the time of Roivant’s exit, Poxel emphasized that the bigger partner’s decision wasn’t due to any efficacy, safety, or other data generated from imeglimin. Phase II development had already been completed and Roivant had positive indications from a meeting with the US Food and Drug Administration (FDA) last year that the drug could be suitable for patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD) – two conditions that often overlap.
However, it’s possible that Roivant and its subsidiary Metavant weren’t prepared to organize and bankroll huge phase III trials, which are often needed when developing treatments for common, competitive indications like type 2 diabetes. This limits the number of advanced biotech and pharma players in the diabetes space to those with the deepest pockets.
Poxel’s CEO and co-founder Thomas Kuhn remains confident that there is a unique role for the drug in treating 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 that is specifically designed to both increase insulin secretion in response to glucose and to reduce insulin resistance,” he told me.
“Because of these effects, we believe that imeglimin has the potential to slow disease progression and provide therapeutic options to patients who no longer respond to current treatments.”
While Poxel did not face immediate financial consequences from Roivant’s withdrawal last year, it acknowledges that it will miss out on up to €506M anticipated under the agreement.
Imeglimin may also face increasingly stiff competition as competitor drugs gain approval and enter the market, particularly for patients with both type 2 diabetes and CKD. One big contender is AstraZeneca’s Farxiga, which blocks a protein called SGLT2. Farxiga received FDA approval in April for treating CKD, with or without type 2 diabetes, and an EU nod is likely to follow shortly.
Drugs that mimic a hormone called Glucagon-like peptide 1 have dominated the type 2 diabetes market for some time, but have not been available as an oral formulation until the approval of Novo Nordisk’s semaglutide by the EU in 2020. With both cardiovascular and weight loss benefits associated with this drug, it will likely be a strong competitor for imeglimin.
New candidates are also in the pipeline, such as Irish biotech Afimmune’s next-generation synthetic omega−3 fatty acid epeleuton. The phase II-stage drug is a derivative of a metabolite of eicosapentaenoic acid (EPA), explained the company’s senior medical director Moayed Hamza. He noted that EPA, marketed by the Dublin-based Amarin as icosapent ethyl, markedly decreases cardiovascular risk.
“There have been substantial 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 new treatments for type 2 diabetes need to improve cardiovascular or renal outcomes to effectively compete, especially in the US and Europe.”
Poxel maintains that it is unaware of any other advanced contenders that act in the same way as imeglimin. By directly targeting mitochondria, the drug can simultaneously target high blood glucose in different organs by restoring insulin secretion in the pancreas, increasing glucose uptake by the muscles, and reducing the amount of excess glucose produced by the liver.
Kuhn points out that the Japanese market is particularly important as the second-largest diabetes market in the world outside the US, with more than 10 million people living with the condition and a compounded annual growth rate that is heading towards 20%. The Japanese authorities are also placing big emphasis on treating and preventing age-related diseases like diabetes as the population ages rapidly.
Poxel had been able to swiftly advance imeglimin with Sumitomo Dainippon Pharma, partly thanks to closely working with the Japanese Pharmaceutical and Medical Devices Agency.
“This resulted in a successful phase III development program with over 1,000 patients lasting only two years followed by the JNDA [Japanese New Drug Application] filing and approval,” he said.
Cover image from Anastasiia Slynko