Johnson & Johnson has moved swiftly ahead with a filing for its diabetes drug Invokana that would include a claim that it can reduce major adverse cardiovascular events (MACE).
The filing is based on the results of the CANVAS trial, which showed that its SGLT2 inhibitor Invokana (canagliflozin) was able to reduce the combined risk of cardiovascular death, myocardial infarction and stroke by 14% compared to placebo in at-risk patients with type 2 diabetes, and also cut the risk of hospitalisation for heart failure by a third.
J&J’s pharma division Janssen is trying to get the cardiovascular outcome claim added to Invokana and its combination products Invokamet and Invokamet XR (canagliflozin and metformin), and if it succeeds will be able to make a strong case for its product to prescribers and payers. Adults with type 2 diabetes are four times more likely to develop cardiovascular disease, and this is the leading cause of death in these patients.
If the FDA approves the label, Invokana could be able to match rival SGLT2 inhibitor Jardiance (empagliflozin) from Eli Lilly and Boehringer Ingelheim, which had cardiovascular outcomes data added to its label in the wake of the EMPA-REG study, as well as Novo Nordisk’s GLP-1 agonist Victoza (liraglutide) which was given a cardiovascular disease reduction indication in August.
“People with type 2 diabetes have a substantially increased risk of developing cardiovascular disease, and it’s encouraging that we now have data to show Invokana may help address this challenge,” said Janssen’s head of cardiovascular and metabolism James List. “Invokana has shown a clear benefit in reducing cardiovascular risk in adults with type 2 diabetes and we look forward to working with FDA as it reviews our filing.”
One issue that could hold back J&J’s Invokana franchise is that of a higher risk of leg and foot amputations, with the FDA requiring a black box warning – its most prominent – on the products’ label earlier this year. The US regulator’s current thinking is that this has only been confirmed with canagliflozin, although the EMA recently suggested that while this has not been seen with other SGLT2 inhibitors, doctors and patients should be vigilant with all drugs in the class.
Analysts have suggested that cardiovascular outcomes data could boost peak sales of Jardiance by up to $1.7bn, and that the amputation issue with Invokana could mean that Lilly and Boehringer’s drug has the most to gain from cardiovascular labelling, threatening Invokana’s current market-leading position. J&J counters that it was only because CANVAS was such a big programme that the safety signal was able to be observed
J&J is hoping to tilt the balance in its favour with a large-scale trial called CREDENCE that will try to show a benefit for Invokana on renal damage in type 2 diabetes – something that was shown in the CANVAS-R companion trial – but Lilly and Boehringer have designs in that area too with an outcomes trial planned for Jardiance in chronic kidney disease patients both with and without diabetes.
AstraZeneca and Pfizer/Merck & Co are the laggards in the category, with AZ not expecting prospective cardiovascular outcomes data for Farxiga (dapagliflozin) until 2019 and Pfizer and Merck still waiting for approval of their ertugliflozin-based products.