Sumitomo Pharma and Poxel Reveal Topline Results from TWYMEEG® Study for Type 2 Diabetes in Japan

Sumitomo Pharma Co., Ltd., headquartered in Osaka, Japan, and Poxel SA, a clinical-stage biopharmaceutical company based in Lyon, France, announced the results of a post-marketing clinical study named TWINKLE. The study focused on the safety and tolerability of TWYMEEG® Tablets 500 mg (imeglimin hydrochloride) in Japanese patients with type 2 diabetes (T2D) and renal impairment. The study was part of a Risk Management Plan for the drug, which began sales in Japan in September 2021.

The TWINKLE study was an open-label, uncontrolled, long-term clinical trial involving 60 Japanese type 2 diabetic patients who also had renal impairment. Participants had either no prior experience with diabetes treatment other than diet and exercise or insufficient control of their blood sugar levels with a single hypoglycemic agent, excluding insulin. The study administered the drug at 500 mg twice daily to those with moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] between 15 mL/min/1.73 m² and less than 45 mL/min/1.73 m²). For patients with end-stage renal disease (eGFR less than 15 mL/min/1.73 m²), the drug was administered at 500 mg once daily. The goal was to assess the safety and tolerability of the oral administration of the drug over a period of 52 weeks.

The study's outcomes indicated that TWYMEEG® was safe and well-tolerated in this patient group. There were no significant differences in the incidence, type, or severity of adverse events compared to previous clinical trials. Most adverse events were mild or moderate. Serious adverse events occurred in 16.7% of participants (10 out of 60), yet none were found to be causally related to the drug. Only a small number of subjects (4 out of 60) discontinued the study due to adverse events.

Currently, TWYMEEG® is not recommended for patients with an eGFR less than 45 mL/min/1.73 m². However, following the results of this study, Sumitomo Pharma plans to engage with Japanese regulatory authorities to discuss potential updates to the drug's package insert by fiscal year 2024, which ends on March 31, 2025.

TWYMEEG® is distinguished as the first agent in a novel class of tetrahydrotriazine-containing molecules. It exhibits a glucose-lowering effect via dual mechanisms: promoting insulin secretion in response to glucose concentration and improving glucose metabolism in the liver and muscles. These actions are facilitated through its activity on mitochondria. The drug is also believed to prevent endothelial and diastolic dysfunction, which can protect against microvascular and macrovascular complications caused by diabetes. It may also support the survival and function of pancreatic beta cells. Due to its unique mechanism, TWYMEEG® is used widely either as a monotherapy or in combination with other treatments for type 2 diabetes.

In October 2017, Sumitomo Pharma entered a partnership with Poxel SA for the development and commercialization of TWYMEEG® in Japan, China, Taiwan, Korea, and nine other Southeast Asian countries. The drug has been available in Japan since September 2021.

Sumitomo Pharma aims to contribute to global healthcare through innovative research and development, focusing on providing valuable pharmaceutical solutions. Meanwhile, Poxel SA continues to develop treatments for chronic serious diseases with metabolic origins, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders.