Clinical study promoted by Eurofarma using evogliptin will be presented in the American Diabetes Conference in June, 7-11, in San Francisco, United States. Evogliptin is an oral antidiabetic from dipeptidyl peptidase-4 (DPP-4) inhibitor class, also known as gliptins.

Evogliptin clinical development started in South Korea in 2009 by Dong-A, and was concluded in 2015. Evogliptin 5 mg was approved by Korean regulatory agency (MFDS – Ministry of Food and Drug Safety) in October 2015 for treatment of type 2 diabetes mellitus.

A bridge study was outlined and conducted in Brazil to confirm evogliptin efficacy and safety, validating the optimal clinical dose of the drug for the local population, and allowing the extrapolation of the results obtained in studies conducted with Asian population to Western population.

Efficacy results obtained confirm for Western population the efficacy of the dose approved for Eastern population (evogliptin 5.0mg). The 5.0mg dose also proved to be safe and well tolerated, and safety issues were not found for the population studied. So, the results of this bridge-study validate for the Brazilian population the dose previously approved for Asian population and allow the extrapolation/validation of the results of studies conducted in the ambit of the product clinical development program for regulatory submission in our country.

This study was conducted in 10 research centers in Brazil (6 in São Paulo, 1 in Rio de Janeiro, 1 in Brasília, 1 in Belém and 1 in Fortaleza), responsible for selecting 226 patients, of which 146 met the study eligibility criteria and were randomized for one of the four treatment arms. Eligible participants received evogliptin in doses of 2.5mg/day or 5.0mg/day or 10mg/day or sitagliptin in dose of 100mg/day, one single daily dose, during 12 weeks.

“Evogliptin is a DPP-4 inhibitor that shares the advantages of the class like strength to reduce blood glucose, neutrality with regard to weight, few adverse events and low hypoglycemia risk. It presents the advantage of higher renal safety, when compared to other drugs of the same class, without need to adjust the dose according to the renal function (clearance) of the patient”, explains Cintia Cercato, coordinator of the study, which was baptized as Evolution.

The agreement between Eurofarma and Dong-A provides for the development and trading of the new drug in Brazil and other 17 Latin American countries, including Mexico. The first countries to have the drug available will be Argentina and Brazil.

“We are honored to establish this partnership with Eurofarma for South and Central Americas and Mexico, in addition to Brazil”, says Chan- il Park, Dong-A ST CEO. “Considering that Eurofarma is the most prescribed corporation in Brazil and keeps on expanding its sales in Latin America, this is a great opportunity for Dong-A to export its technology and new drugs to the whole region”, adds the executive. Maurizio Billi, Eurofarma president, on the other hand, reveals: “We intend to expand our partnership with focus on the development of innovative products in Brazil and Latin America”.

Evolution Study1

Evogliptin is an oral antidiabetic from dipeptidyl peptidase-4 (DPP-4) inhibitor class, also known as gliptins.

Evogliptin clinical development started in South Korea in 2009 by Dong-A ST Co., and was concluded in 2015. The product (Evogliptin 5mg) was approved by Korean regulatory agency (MFDS – Ministry of Food and Drug Safety) on October 10, 2015 for treatment of type 2 diabetes mellitus (DMT2). The commercial name of the product approved is Suganon®.

Since Eurofarma Laboratórios S.A. intends to register the product in Brazil, a bridge-study was outlined and conducted in Brazil to confirm evogliptin efficacy and safety, validating the optimal clinical dose of the drug to the local population, and allowing the extrapolation of the results obtained in studies conducted with Asian population to Western population.

This study was conducted in 10 research centers in Brazil (6 in São Paulo, 1 in Rio de Janeiro, 1 in Brasília, 1 in Belém and 1 in Fortaleza), responsible for selecting 226 patients, of which 146 met the study eligibility criteria and were randomized for one of the four treatment arms. Eligible participants received evogliptin in doses of 2.5mg/day or 5.0mg/day or 10mg/day or sitagliptin in dose of 100mg/day, one single daily dose, during 12 weeks.

Efficacy assessment was made based on the absolute variation of levels of HbA1c (glycated hemoglobin, in %), fasting blood glucose (mg/dL) and body weight (kg) established between the basal period (selection visit) and 12 weeks after the treatment started (final visit). Safety assessment was based on reports of adverse events (AEs), findings in physical examination, vital signs, and electrocardiogram tracing (ECG).

All treatment arms of the study proved to be safe and well tolerated and no alerts were observed related to evogliptin safety. Deaths were not reported during the study and the findings of physical examination and vital signs did not culminate in safety alerts. The same was observed for safety laboratory exams and ECG. The profile of AEs reported corresponded to what was expected for IDPP4 therapeutic class.

Primary analyses of efficacy, conducted with all eligible patients included in the study (N = 146), showed average reduction of levels of HbA1c statistically and clinically significant in all treatment groups, with absolute variation inferior to -0.5%, indicating the clinical benefit of all treatments of the study. The average variation (within 90% confidence interval) of HbA1c level observed 12 weeks after the start of the treatment with evogliptin 5.0mg was -1.12% (-1.4%; -0.8%), value that indicates the clinical benefit of this IDPP4 in the population evaluated.

The reduction of HbA1c observed in all groups was higher than usually observed when IDPP4 is administered in mono-therapy, which can only be explained by the initial (basal) HbA1c level of the population studied, which was very high.
With regard to fasting blood glucose, average reduction of 18.94mg/dL (-31.8 mg/dL; -6.1 mg/dL) was observed 12 weeks after the beginning of treatment with evogliptin 5mg.

The average variation (within 90% confidence interval) of weight after 12 weeks of treatment was -1.19kg (-1.7kg ; -0.7kg) in the group treated with evogliptin 5.0mg. This weight loss is according to what is expected for this therapeutic class in this population.
The observation of results obtained in the several treatment groups showed that, compared to evogliptin dose of 2.5mg, the administration of evogliptin 5.0mg showed similar reduction in HbA1c levels, however with better control of fasting blood glucose, favoring the administration of daily dose of 5.0mg. As to evogliptin 10mg, average reductions observed in HbA1c and fasting blood glucose levels were similar, also favoring daily dose of 5.0mg (the smaller of the two doses associated to consistent clinical benefit). Moreover, the results obtained in evogliptin 5mg treatment arm proved to be similar to those obtained with sitagliptin 100mg, validating the methodology and the population of the study.

These efficacy results obtained confirm for the Western population the efficacy of the dose approved for the Eastern population (evogliptin 5.0mg). The 5.0mg dose also proved to be safe and well tolerated, and no safety issues were found for the population studied. Thus, the results of this bridge-study validate for the Brazilian population the dose previously approved for the Asian population and allow the extrapolation/validation of the results of studies conducted in the ambit of the product clinical development program for regulatory submission in our country.

 

1 – Forti, A.C.; Felicio, J.S.; Russo, L.A.; Borges, J.L; Salles, J.E.; Cercato, C. “Efficacy and Safety of Evogliptin in a Brazilian T2DM Population – A Bridging Study”. American Diabetes Association, San Francisco, CA, USA. June 9th 2019. General Poster Session: 1005-P.