FDA Votes to Change Jardiance Label to Show Reduction in Heart-Related Deaths

Close 12-11 vote in favor of label update. Plus, nearly 40% reduction in kidney disease shown at ADA.

In a close 12-11 vote, an FDA advisory panel voted yesterday in favor of changing the drug label of Jardiance (empagliflozin, an SGLT-2 inhibitor pill) to reflect a reduction in death from heart-related disease seen with Jardiance during a major heart safety clinical trial: the “EMPA-REG OUTCOME trial.” The trial observed over 7,020 adults with type 2 diabetes with an established history of heart disease taking Jardiance in addition to the "standard of care" for heart disease risk reduction (e.g., statins, blood pressure lowering drugs, aspirin, etc.) and diabetes care (most participants were taking other diabetes medications as well). Advisory panel members felt that the strong reduction in heart-related death during the trial was convincing. However, some members had reservations because Jardiance did not reduce non-fatal heart attacks or non-fatal strokes in the trial (see more below); but lower death certainly means a great deal from a patient perspective, that’s for sure! As we have been writing for some time, we also want to make sure patients are as healthy as possible, at every point in their diabetes journey. It’s now up to the FDA to decide if this information about death reduction will make it onto the label for Jardiance – we expect a decision toward the end of the year, so stay tuned!

Additionally, we saw new kidney safety data from the EMPA-REG OUTCOME trial at the ADA 2016 Scientific Sessions, which showed that Jardiance reduces the risk of kidney disease by 39% in people with type 2 diabetes with an established history of heart disease. Jardiance was shown to preserve kidney function (as measured by “estimated glomerular filtration rate,” or eGFR) after a small initial decrease in function, whereas people not on Jardiance experienced steadily worsening kidney function throughout the trial. Obviously people with diabetes want as healthy kidneys as possible, so this news was a big win. We do emphasize that this trial was in patients who were at very high risk of heart disease – so these results are not applicable to all patients. On another exciting note, data from this major clinical trial also showed a reduction in several additional outcomes related to kidney impairment, including starting dialysis therapy (55% reduction). Kidney disease needs much more attention and focus, so the news that Jardiance demonstrates a significant risk reduction, even in this specific high risk population, is groundbreaking.

These additional data come just nine months after Lilly/BI announced that Jardiance improved heart safety in this same group of patients (high risk type 2 patients with heart disease). The EMPA-REG OUTCOME trial showed that when Jardiance was added to existing care, the drug led to:

• a 14% reduction in total “cardiovascular events” (heart attacks, strokes, heart-related deaths)

• a 38% reduction in risk of heart-related death

• a 32% reduction in overall death

• a 35% reduction in hospitalizations from heart failure

That said, the trial did reveal a slightly higher rate of strokes in people treated with Jardiance, though this was “non-statistically significant,” meaning it may have been due to chance. These results are very relevant for those with type 2 diabetes and heart disease, though again they cannot be generalized to all people with type 2 diabetes. For more details about the trial and the full results, see here.

Jardiance is the first diabetes drug to demonstrate improved kidney health, but it’s not the only one. At the same conference earlier this month, exciting news broke from Novo Nordisk’s LEADER clinical trial showing that Victoza, a once-daily GLP-1 agonist injection, also significantly reduces the risk of cardiovascular death, kidney disease, and hypoglycemia in people with type 2 diabetes with a history of heart disease. Note, this “cardio-protection” was seen primarily in those with an established history of cardiac disease – in other words, people with advanced diabetes. Those who only showed risk factors for heart disease (high blood pressure, high cholesterol, etc.) did not see a significant benefit - though this may just be because there were comparatively few patients in the trial at high risk for heart disease but no established heart disease. You can read more about LEADER in our recent coverage, and if you want all the scientific background that your healthcare team is looking at, you can read the full results in the New England Journal of Medicine. –CA/HG/KC