ADA 2016: Ertugliflozin data suggest promising fixed-dose combination with market leader Januvia.
By Kevin Shannon, Analyst
20 June 2016
I am an analyst at Datamonitor Healthcare, currently located in San Diego, California, where I am a member of the cardio...
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Data from trials investigating ertugliflozin (Merck & Co/Pfizer) as a monotherapy and in combination with Januvia (sitagliptin; Merck & Co) were presented on 12 June at the American Diabetes Association’s 76th Scientific Sessions (ADA 2016) in New Orleans. Results were as expected, with ertugliflozin demonstrating solid glycated hemoglobin (HbA1c) reductions and meeting its primary endpoint in both trials. As a monotherapy, ertugliflozin did not demonstrate any differentiating factors from current sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and is likely to experience moderate uptake as a result. However, the fixed-dose combination (FDC) therapy with Januvia demonstrated superiority over either component alone, and holds advantages over current dipeptidyl peptidase-IV (DPP-IV)/SGLT-2 inhibitor FDCs.
Trial data from both investigations presented at ADA 2016 were ultimately positive, with both trials meeting primary and secondary endpoints. Ertugliflozin in combination with sitagliptin demonstrated promising HbA1c reduction, showing strong potential for an FDC. As a monotherapy, ertugliflozin did not differentiate itself from current SGLT-2 inhibitors. Ertugliflozin was found to have differences in mean HbA1c reduction of -0.99% and -1.16% relative to placebo when dosed at 5mg daily and 15mg daily, respectively, in the VERTIS Mono trial (Dagogo-Jack et al., 2016). In the VERTIS Factorial trial, ertugliflozin in combination with sitagliptin was found to be superior to either ertugliflozin or sitagliptin alone; the combination therapy was found to have a mean HbA1c reduction of 1.5% (15mg ertugliflozin + 100mg sitagliptin) compared to 1.1% with both 15mg ertugliflozin and 100mg sitagliptin as monotherapies (Eldor et al., 2016).
Overview of efficacy data for ertugliflozin compared to placebo in the VERTIS Mono trial
|Endpoint||Ertugliflozin 5mg||Ertugliflozin 15mg|
|Difference in mean HbA1c reduction relative to placebo||-0.99%||-1.16%|
|HbA1c = glycated hemoglobin|
|Source: Dagogo-Jack et al., 2016|
Overview of efficacy data for ertugliflozin + sitagliptin compared to placebo and individual products in the VERTIS Factorial trial
|Endpoint||Ertugliflozin 5mg||Ertugliflozin 15mg||Sitagliptin 100mg||Ertugliflozin 5mg + sitagliptin 100mg||Ertugliflozin 15mg + sitagliptin 100mg|
|HbA1c reduction from baseline||-1.0%||-1.1%||-1.1%||-1.5%||-1.5%|
|HbA1c = glycated hemoglobin|
|Source: Eldor et al., 2016|
Merck’s deal negotiated with Pfizer has allowed for the development of an FDC therapy with the market-leading oral antidiabetic and DPP-IV inhibitor Januvia. This combination is likely to gain strong traction due to Januvia’s widespread use in the market, making this FDC a significantly more convenient option than its competitors. An FDC of ertugliflozin + sitagliptin would not require a physician to switch a patient from Januvia to another DPP-IV inhibitor brand when intensifying therapy with an FDC, and this provides the drug with a significant advantage over rival SGLT-2/DPP-IV FDCs Glyxambi (empagliflozin/linagliptin; Boehringer Ingelheim/Eli Lilly) and SaxaDapa (dapagliflozin/saxagliptin; AstraZeneca) given the physician and patient familiarity associated with Januvia.
Ertugliflozin monotherapy is expected to face difficulty breaking into the already saturated SGLT-2 inhibitor market. There are currently three SGLT-2 inhibitor franchises already on the market in the US, Japan, and Europe, all of which were launched in 2014 or earlier. Current trial data have not shown any advantages of ertugliflozin monotherapy over currently marketed SGLT-2 inhibitors, giving physicians little incentive to switch.
Dagogo-Jack S, Davies M, Frias J, Derosa G, Darekar A, Focht K, Golm G, Johnson J, Saur D, Terra S (2016) Ertugliflozin Effectively Improves Glycemic Control as Monotherapy in Patients with T2DM. Abstract number: 130-LB; American Diabetes Association 76th Scientific Sessions, 10–14 June, New Orleans.
Eldor R, Pratley R, Golm G, Huyck S, Qiu Y, Sunga S, Johnson J, Terra S, Mancuso J, Engel S, Lauring B (2016) Effect of Ertugliflozin plus Sitagliptin on Glycemic Control vs. Either Treatment Alone in Subjects with T2DM Inadequately Controlled with Metformin. Abstract number: 125-LB; American Diabetes Association 76th Scientific Sessions, 10–14 June, New Orleans.
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