Janssen has won approval from US regulators for its new diabetes drug Invokana (canagliflozin), in a decision that will make it the first in its class to reach the market in the States.
A sodium-glucose co-transporter 2 (SGLT2) inhibitor, Invokana works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetics who have elevated blood glucose levels.
“Invokana provides patients with type 2 diabetes the option of a once-daily oral therapy that offers improved glycaemic control and, in phase 3 studies, showed an incidence of hypoglycaemia – low blood glucose – that was lower than with glimepiride [Sanofi’s Amaryl] and similar to that of sitagliptin [Merck & Co’s Januvia],” said Jimmy Ren, therapeutic area lead, metabolics, medical affairs, Janssen Pharmaceuticals.
“In addition, this new treatment option is associated with reductions in body weight and systolic blood pressure,” he added.
The FDA approved Invokana to be used with diet and exercise to improve glycaemic control in adults with type 2 diabetes, the most common form of the disease.
The approval came on the back of nine clinical trials involving over 10,285 patients that showed improvements in haemoglobin A1c levels (a measure of blood sugar control) and fasting plasma glucose (blood sugar) levels.
But the regulator warned that Invokana should not be used to treat people who have increased ketones in their blood or urine (diabetic ketoacidosis), or in those with severe renal impairment, end stage renal disease, or in patients on dialysis.
The most common side effects of Invokana are vaginal yeast infection (vulvovaginal candidiasis) and urinary tract infection. Because Invokana is associated with a diuretic effect, it can cause a reduction in intravascular volume leading to orthostatic or postural hypotension (a sudden fall in blood pressure when standing up).
As part of its approval Janssen will have to carry out five post-marketing studies for Invokana, including a cardiovascular outcomes trial.
The FDA has been on a heightened alert over the safety of diabetes drugs ever since GSK’s Avandia was found to increase the risk of cardiovascular events and had its use limited in the US in 2011.
The regulator, which recently launched an investigation into the risk of pancreatitis with two types of diabetes drugs, also wants Janssen to conduct an enhanced pharmacovigilance programme to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes.
The pharma company will also have to carry out a bone safety study and two paediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study.
Nevertheless, Invokana’s US approval could give it an edge over rival SGLT2 drugs like AstraZeneca/Bristol-Myers Squibb’s Forxiga (dapagliflozin), which has been approved in Europe but delayed in the US, and Boehringer/Lilly’s empagliflozin, which has recently been filed for approval in the US and Europe.