FDA and EMA accept Merck/Pfizer’s ertugliflozin and fixed-dose combinations for regulatory review – March 7, 2017

Executive Highlights

  • The FDA has accepted three New Drug Applications (NDAs) for Merck/Pfizer’s SGLT-2 inhibitor ertugliflozin, as well as fixed-dose combinations of ertugliflozin/metformin and ertugliflozin/sitagliptin (Merck’s DPP-4 inhibitor Januvia). The EMA has also accepted Marketing Authorization Applications (MAAs) for all three products.
  • Assuming a standard 10-month review process, an FDA decision on all three NDAs is expected by January 2018.

Merck/Pfizer announced Monday morning that the FDA and EMA have accepted their SGLT-2 inhibitor candidate ertugliflozin, along with fixed-dose combinations of ertugliflozin/metformin and ertugliflozin/sitagliptin (Merck’s DPP-4 inhibitor Januvia), for regulatory review. Assuming a standard 10-month review process, FDA and EMA decisions are expected by January 2018. Merck CEO Mr. Ken Frazier shared at JPM 2017 that three separate New Drug Applications (NDAs) had been submitted to the FDA late last year, based on positive results from the VERTIS clinical program and especially the VERTIS SITA2 trial presented at EASD 2016. We’re happy to see the ertugliflozin family of products move forward within the FDA and EMA regulatory review process – data thus far has shown superior A1c-lowering, reductions in fasting plasma glucose, reductions in systolic blood pressure, and weight loss vs. placebo. We’re especially pleased that all three formulations – standalone ertugliflozin and the two combinations – will be available in a similar timeframe. We were lucky to speak with Merck’s Associate VP of clinical research in diabetes Dr. Sam Engel about this news. As he put it, “With the three formulations, we’re really able to address patients’ needs across the spectrum of diabetes treatment, whether it’s as a monotherapy, as an add-on to metformin, or in a dual combination with sitagliptin.”

  • If approved, ertugliflozin will be the fourth major SGLT-2 inhibitor product on the market, following J&J’s Invokana (canagliflozin), AZ’s Farxiga (dapagliflozin), and Lilly/BI’s Jardiance (empagliflozin). All three franchises also feature a fixed-dose combination with metformin (Invokamet, Xigduo, and Synjardy, respectively). Notably, it appears that the ertugliflozin/metformin combination will be dosed twice-daily, whereas once-daily extended-release formulations of the other SGLT-2 inhibitor/metformin combinations are available on the US market. Ertugliflozin/sitagliptin would join an emerging class of SGLT-2/DPP-4 combinations – AZ’s Qtern (dapagliflozin/saxagliptin) was only recently approved by the FDA, while Lilly/BI’s Glyxambi (empagliflozin/linagliptin) has been on the market since 2015 but has posted sluggish sales to-date.
    • In our view, expanded patient choice is an exceptionally good thing, especially for a new class like SGLT-2 inhibitors – these agents have shown tremendous glycemic and other health benefits, including possible cardio- and renal-protection. The class is growing, with sales up 48% YOY in 4Q16 and up 44% YOY in 2016 to $2.9 billion. We expect that the recent label update for Jardiance to indicate reduction of CV death (along with the potential for a cardioprotective class effect) will accelerate this growth of the entire class in 2017. All this is to say that we see plenty of room for four companies to sustain a successful SGLT-2 inhibitor business, and we hope that more people with diabetes can access these effective medicines in the near-future.
  • A cardiovascular outcomes trial (CVOT) for ertugliflozin, VERTIS CV, is ongoing. According to, the trial is expected to complete in October 2019. As CVOTs gain more traction, and as the field increasingly emphasizes CV risk reduction for best practice diabetes management, we think any new drug’s long-term commercial success will depend on demonstrating compelling CV safety (at the very least), if not a pronounced CV benefit. This is especially true for the SGLT-2 inhibitor class, where Jardiance is already indicated for the reduction of CV death based on findings from EMPA-REG OUTCOME. The CANVAS trial for Invokana will report full results at ADA 2017. While Dr. Engel emphasized that it’s premature to speculate on the VERTIS CV results, he pointed to Merck’s decision to expand the trial to over 8,000 patients as evidence that the company is “encouraged and optimistic about the future.”
  • With this news, we’re glad to see Merck and Pfizer expand their presence in diabetes. Merck is already a diabetes powerhouse with DPP-4 inhibitor Januvia (a leading type 2 prescription medicine by volume) and now has the potential to grow its diabetes business even further with ertugliflozin as well as biosimilar insulin glargine MK-1293 (filed with the FDA in 3Q16; currently facing a patent infringement lawsuit from Sanofi). Pfizer’s other diabetes-related pipeline products are all in phase 1: an undisclosed biologic for type 1 diabetes, an undisclosed biologic for type 2 diabetes, and two undisclosed small molecules for NASH. In disappointing (though not entirely unexpected) news, Pfizer recently discontinued its phase 2 glucagon receptor (GCGR) antagonist, likely due to safety concerns associated with the class (Dr. Ralph DeFronzo spoke to these issues at AACE 2015). Given this context, we’re especially glad to note Pfizer’s commitment to ertugliflozin and the company’s continued involvement in diabetes.

-- by Payal Marathe, Abigail Dove, Helen Gao, and Kelly Close