ESC – Case builds for Jardiance

Chances for Jardiance moving to earlier diabetes treatment lines have risen even further with presentation of new heart failure data for Januvia and Lyxumia at the European Society of Cardiology meeting today.

The last two drugs are not harmful to the hearts of diabetics, but cannot show any protective benefit, unlike that suggested for Jardiance by the results of the Empa-Reg Outcomes trial. Specialists are anxiously awaiting results, but if the full Empa-Reg data are as positive as Eli Lilly and Boehringer Ingelheim have suggested so far, it is likely that diabetes guidelines will be changed to push early-line use of Jardiance, and possibly all of the SGLT-2 class.

“It deserves very careful consideration,” University of Alberta cardiology professor Paul Armstrong said of revising diabetes guidelines to account for Jardiance’s potential cardiovascular benefit. “All of us look forward to seeing that the data that has been suggested is validated at a scientific forum.”

No risk, no benefit

Neither the Elixa trial of GLP-1 Lyxumia nor the Tecos trial of Januvia had revealed broad cardiovascular risk to diabetics who use the drugs, confirming earlier studies of blood-sugar lowering drugs such as Onglyza (Januvia's surprising all clear, courtesy of Tecos, April 28, 2015). Regulators are demanding long-term outcomes for diabetic drugs because of the numbers of patients taking them, heightened cardiovascular risk in the disease, and the events like post-marketing trials showing Avandia’s increased danger of heart attacks.

For Lyxumia, its Elixa study was the first time cardiovascular outcomes for a GLP-1 agent had been disclosed, and it eliminated the likelihood of reduced uptake because of any risk (GLP-1s' first outcomes study unlikely to lift Lyxumia, March 19, 2015). The additional news at ESC was that it has no specific effect on heart failure risk, with a statistically similar hospitalisation rate in both patients who had no history of a previous heart failure admission – 2.4% for Lyxumia and 2.5% for placebo patients – and those who had a previous admission – 9.7% for Lyxumia and 10.2% for placebo.

In Tecos, the profile is very similar. Dr Armstrong reported that 345 of 7,332 patients taking Januvia in the intent-to-treat population had been admitted for heart failure, compared with 347 of 7,339 taking placebo. For patients with previous heart failure, the numbers were 97 of 1,303 taking Januvia and 94 of 1,340 taking placebo.

This spells good news for Januvia, as the DPP-IV class of which it is a part had been under scrutiny for heart failure risk.

You gotta have heart (benefit)

The lack of benefit, however, works against both of those agents when compared with the topline data indicating a cardiovascular benefit for Jardiance. It was already considered the third-best choice in first-line monotherapy after metformin and the GLP-1s, according to endocrinologists’ guidelines, its major flaw being increased genito-urinary infections as a result of its mechanism of action, increased sugar excretion.

The next opportunities for Boehringer and Lilly to present the Empa-Reg Outcomes trial are at the European Association for the Study of Diabetes meeting in September and the American Heart Association scientific sessions in November, and the full data set will be useful for assessing whether specialists will be keen to move Jardiance ahead of Sanofi’s Lyxumia, Novo Nordisk’s Victoza, and other entries from the GLP-1 class – Victoza’s own outcomes trial, called Leader, looks to read out later this year, and has the potential to offer a GLP-1 fightback.

It could prove to be a class effect, but this might only be revealed as more studies read out; data on AstraZeneca’s Farxiga is expected in 2019 and on Johnson & Johnson’s Invokana in 2020. For now, Jardiance has the upper hand. Should the data prove to be as solid as the topline announcement suggests, expect forecasts and uptake to rise.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @ByJonGardner on Twitter

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