Invokana might never be able to shake off its safety issues, but at least on cardiovascular benefit it should be able to match its main rival. Data revealed at the American College of Cardiology meeting show a benefit in preventing heart failure among diabetics taking the Johnson & Johnson pill, which should help it win the FDA’s blessing to begin marketing on that claim, putting it on a par with Lilly and Boehringer’s Jardiance.
The latest analysis from the Canvas study further clarifies how Invokana prevents poor cardiovascular outcomes, with the drug showing a strong improvement over placebo in preventing heart failure hospitalisation as well as cardiovascular death. With diabetes specialists interested not just in heart safety but also in preventing death and complications from cardiovascular causes, showing a benefit is now a must for any glucose-lowering drugs.
Heart don't fail me now
The primary analysis from Canvas showed a statistically significant 14% reduction in the risk of a composite of cardiovascular death and non-fatal myocardial infarctions or strokes, but missed statistical significance on these individual outcomes when measured independently (ADA – Canvas paints a mixed picture for J&J’s Invokana, June 12, 2017).
At ACC, an additional analysis of heart failure among patients enrolled into Canvas revealed that Invokana resulted in a 22% reduction in a composite of cardiovascular death or heart failure hospitalisation, and a 33% decrease in heart failure hospitalisation, versus placebo. In patients with a history of heart failure the result was more pronounced, with a 39% reduction in the composite of cardiovascular death or heart failure hospitalisation.
“These agents are very potent and they’re going to be more expensive than first-line agents for diabetes,” Hadley Wilson, of the Sanger Heart and Vascular Institute in North Carolina, told EP Vantage. “But if you target the at-risk group, the heart failure patients, you’ll see more benefit. One of the best aspects of this study is it identified an at-risk group.”
A cardiovascular benefit is vital for Invokana to stem the losses it has seen since the risk of amputation had to be added to its label (Amputation risk adds another cut to Invokana, May 30, 2017). Its main rival from the SGLT-2 class, Jardiance, has already won the right to be marketed on heart health, and without a similar claim Invokana risks slipping even further.
“It used to be that lowering blood sugar was adequate,” Robert Cuddihy, vice-president of cardiovascular and metabolism medical affairs with J&J, told EP Vantage. “The trouble was that we weren’t having a major impact on the leading morbidity and mortality in diabetes patients, and that’s cardiovascular.”
The evidence of a class effect for all SGLT-2 inhibitors, also including Astrazeneca’s Farxiga, has been growing thanks in part to the CVD-Real analysis (ACC – Jardiance heart benefit looks like a class effect, March 20, 2017).
A second round of this registry, which included patients from the Pacific Rim, Canada and Israel, was presented at ACC and affirmed these findings, showing a benefit for the class when compared with other glucose lowering-drugs on death by any cause, heart failure hospitalisation, myocardial infarction and stroke.
If this class effect is confirmed by, for example, the Declare-Timi trial of Farxiga due later this year, Invokana will face some difficulty. Its main differentiator is the amputation risk, which neither Jardiance nor Farxiga carry on their labels, and which helps explain why Invokana has slipped from number two to number three in this class.
Mr Cuddihy noted the low event rate for amputations – which happened in the placebo cohort as well as in active treatment in Canvas – and said real-world analyses would shed more light on the magnitude of the risk.
Teasing this out will be the next task for J&J with Invokana. But, for now, the company can breathe a little easier knowing that the evidence for the drug’s cardiovascular benefit continues to strengthen.