Rockville, MD - The US Food and Drug Administration (FDA) has approved a novel glucose-lowering agent, canagliflozin (Invokana, Janssen Pharmaceuticals) for the treatment of adults with type 2 diabetes.
Canagliflozin is the first in a new class of drug, an oral inhibitor of sodium glucose cotransporter 2 (SGLT2). Inhibition of SGLT2 reduces resorption of glucose in the kidney, resulting in increased urinary glucose excretion, with a consequent lowering of plasma glucose levels as well as weight loss.
The authorization follows a 10 to 5 vote in favor of approval of canagliflozin by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee in January, despite concerns about the cardiovascular safety of the drug.
The majority of panel members who supported the drug cited the unmet need for new agents to treat the growing population of patients with type 2 diabetes and canagliflozin's absence of hypoglycemia, combined with the potential for weight loss, as deciding factors.
But the panel voted 8 to 7 at the same meeting that it had concerns about the cardiovascular safety of canagliflozin, most particularly a possible elevated risk for stroke. In the end, they deemed that current data were insufficient to be certain about this risk and concluded that longer-term follow-up will be required, including completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS).
CANVAS is an ongoing study being conducted by Janssen in compliance with FDA guidance, issued in 2008, requiring cardiovascular-outcomes data for all new diabetes drugs. Final results of CANVAS are not expected until 2015.
Postmarketing studies required
In today's announcement, the FDA listed five postmarketing studies for canagliflozin that Jansen Pharmaceuticals must conduct as a condition for the drug's approval:
A cardiovascular outcomes trial (CANVAS).
An enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, and other adverse events.
A bone-safety study.
A pediatric pharmacokinetic and pharmacodynamics study.
A pediatric safety and efficacy study.
Clinicians should not use canagliflozin to treat patients with type 1 diabetes or patients with type 2 diabetes who have increased ketones in their blood or urine, severe renal impairment or end-stage renal disease, or those receiving dialysis.
Vaginal yeast infection and urinary-tract infection are the most common adverse events for canagliflozin. Patients may also experience dizziness or fainting, especially in the first three months of therapy, because canagliflozin is associated with a diuretic effect, which can reduce intravascular volume leading to orthostatic or postural hypotension.
Canagliflozin is the first SGLT2 inhibitor to reach the market in the US, but another drug in this class, dapagliflozin (Forxiga, Bristol-Myers Squibb/AstraZeneca), is already available in Europe; it was approved there in November 2012. The FDA denied approval of dapagliflozin in January 2012 because of concerns about a cancer signal.
Canagliflozin, which has also been submitted for approval in the European Union, does not appear to share that risk, with no signal for an increase in malignancy in about 8000 person-years of exposure.
A third SGLT2 inhibitor, ipragliflozin (Astellas Pharma), has been filed for marketing approval in Japan, and a fourth, empagliflozin (Eli Lilly/Boehringer Ingelheim), is in phase 3 trials and has just been filed for approval in the US.
Heartwire from Medscape © 2013
Cite this: FDA approves new diabetes drug, canagliflozin, despite CV concerns - Medscape - Mar 29, 2013.