That Jardiance has become the first diabetes drug proven to prevent the cardiovascular consequences of diabetes rather than simply lowering blood sugar comes as a surprise, and a nice one for Eli Lilly and Boehringer Ingelheim.
It seems likeliest that the result points to an effect common to all the SGLT2 inhibitors, but until the cardiovascular outcomes studies report for the other marketed SGLT2s, Invokana and Farxiga, Jardiance will be the only product that can market on the claim (see table below). And if a class effect is shown, the SGLT2s will pull ahead of the DPP-IV inhibitors in the treatment cascade, spurring sales further.
Detailed results of the Empa-Reg Outcome trial have not been released – all that Lilly and Boehringer have said is that Jardiance was statistically significantly better than placebo at reducing the risk of heart attack, stroke and cardiovascular death. But that’s enough for now. The 7,000-patient, five-year trial had not been expected to show a benefit, not least because no diabetes drug, including insulin itself, ever had.
The feat is more impressive still given that Empa-Reg Outcome was half the size of the Tecos outcomes study assessing Merck & Co’s Januvia and less than half the size of the Savor study of AstraZeneca’s Onglyza, neither of which showed an advantage. As DPP-IV inhibitors, these are currently used in preference to the SGLT2s – Januvia is forecast to be the biggest seller of this class, with $4.7bn in worldwide sales in 2020. This is more than twice as much as the top-selling SGLT2 inhibitor, Johnson & Johnson’s Invokana.
Both of these situations could change over the coming months, with the newer drug class supplanting the DPP-IVs and Jardiance taking the top spot from Invokana. Analysts at Cowen & Co wrote that Jardiance could become the oral drug of choice after metformin.
That said, SGLT2s and DPP-IVs are often taken together, so while sales of the former might grow, sales of the latter might not necessarily shrink drastically.
Window of opportunity
Jardiance’s new marketing advantage might also go some way to compensating for its big disadvantage. Like all of its class, its label warns of vaginal infection risk, but alone among the approved SGLT2s, Jardiance also increases the risk of urinary tract infections.
But before the label can be updated full data will have to be presented, and this is scheduled for the EASD meeting in Stockholm next month. They will be scrutinised for safety signals that have emerged in previous diabetes drug outcome studies, such as hospitalisation for heart failure and diabetes ketoacidosis.
After that, there will be a two-year wait to find out if it is just Jardiance that guards against heart attack, stroke and death, or if similar compounds do too. Invokana’s Canvas trial will be the next to read out, followed by trials of AstraZeneca’s Farxiga in 2019 and Pfizer’s not-yet-marketed ertugliflozin a year later.
In the meantime, though, a cardio outcome study of yet another class of antidiabetics will report. Data from the outcomes trial of Novo Nordisk’s Victoza, a GLP-1 inhibitor, are expected before the end of 2015.
One GLP-1 has already reported outcomes data, and of course it missed. Sanofi’s Lyxumia failed to show a benefit earlier this year but as it is thought to be weaker than Novo Nordisk’s drug the result might not necessarily be a washout.
Boehringer and Lilly must hope that it is. Then they can make the most of their window before Invokana – if its trial hits – starts muscling back in.
|SGLT2 inhibitors and their outcomes trials|
|Product||Company||WW sales 2013 ($)||WW sales 2020 ($)||First approval date||Cardiovascular outcomes data due*||Trial name||Trial ID|
|Invokana||Johnson & Johnson||141||2,105||March 1, 2013||April 1, 2017||Canvas||NCT01032629|
|Farxiga||AstraZeneca||-||1,455||January 1, 2014||April 1, 2019||Declare||NCT01730534|
|Jardiance||Boehringer Ingelheim/ Eli Lilly||-||1,439||August 1, 2014||Hit||Empa-Reg Outcome||NCT01131676|
|ertugliflozin||Pfizer||-||396||Expected December 2017||July 1, 2020||-||NCT01986881|
|*Data collection date for primary outcome measure according to ClinicalTrials.gov|