Regulators in the USA have given the green light to Johnson & Johnson's Invokana, the first in a new class of diabetes drugs.
Invokana (canagliflozin) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor which works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels. Its safety and effectiveness were evaluated in nine trials involving 10,285 patients with type 2 diabetes which showed improvement in haemoglobin A1c levels and fasting plasma glucose levels.
The approval was expected given that at the beginning of the year, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted 10-5 in support of canagliflozin. However, the panel noted concerns about potential cardiovascular risks, while some members recommended that patients with impaired kidneys should not be given the drug.
Five postmarketing studies needed
In approving Invokana, the FDA agreed that the drug should not be used in patients with severe renal impairment, end stage renal disease, or in patients on dialysis, nor by diabetics who have increased ketones in their blood or urine. The agency did make any specific mention of the heart issues but is insisting on five postmarketing studies, including a cardiovascular outcomes trial.
The FDA also requires an enhanced pharmacovigilance programme to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities and adverse pregnancy outcomes. It also wants to see a bone safety study and two paediatric trials.
The most common side effects of Invokana, which is licensed from Japan's Mitsubishi Tanabe Pharma Corp, are vaginal yeast infection and urinary tract infection. Because it is associated with a diuretic effect, it can cause a reduction in intravascular volume leading to orthostatic or postural hypotension, which may result in symptoms such as dizziness or fainting, and is most common in the first three months of therapy.
Commenting on the thumbs-up, Jimmy Ren, head of metabolic medical affairs at J&J's Janssen Pharmaceuticals, said Invokana provides patients with the option of a once-daily oral therapy that offers improved glycaemic control which is associated with reductions in body weight and systolic blood pressure.
Last year, AstraZeneca and Bristol-Myers Squibb's SGLT2 inhibitor Forxiga (dapagliflozin) was rejected by the FDA on safety concerns, although it did win clearance in Europe. Last week, Boehringer Ingelheim and Eli Lilly's empagliflozin was filed on both sides of the Atlantic.