Despite lingering skepticism about whether interim data from an ongoing cardiovascular trial would be enough to convince FDA to clear an NDA, Johnson & Johnson’s Janssen Pharmaceuticals Inc. unit gained approval for its type 2 diabetes treatment Invokana (canagliflozin) on March 29.

The drug has been tested in nine clinical trials in more than 10,000 patients, both as a standalone therapy, and in conjunction with other diabetes treatments, including metformin and insulin. It has not been approved for treatment of type 1 diabetes or for patients with any stage of renal impairment.

FDA is requesting Janssen conduct five post-marketing studies, including a cardiovascular outcomes trial, pediatric studies, a bone safety study, and an enhanced pharmacovigilance study to monitor several safety issues, including malignancies and pancreatitis. Janssen has already begun the 4,385-patient CANVAS CV outcomes trial – interim results from the trial were included in the NDA submission for the drug, and the agency indicated previously that it is willing to accept CANVAS CV’s final outcome as proof of whether the drug meets the post-marketing CV requirements. The trial is expected to complete in 2015 Also see "Use Of Pre-Approval CV Data From Ongoing Trial Gets Once-Over At Canagliflozin Panel" - Pink Sheet, 21 January, 2013..

The drug received a 10-5 endorsement from FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on Jan. 10. While the agency often follows the recommendation of its panels, it is not required to. Several panel members voiced concern that low efficacy in patients with moderate levels of renal impairment on top of the potential for additional renal damage produces a negative benefit/risk assessment ([A#14130110005]).

First SGLT-2 To Market

The drug is the first approved of a new class of diabetes treatments, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, which work to remove excess glucose through the urine by blocking re-absorption in the kidneys. Due to its mechanism of action, the class is known to cause urinary tract infections and is not well-tolerated in renal patients.

Janssen is certainly not the only Big Pharma with an SGLT-2 inhibitor in development: Bristol-Myers Squibb Co./AstraZeneca PLC received a “complete response” letter from FDA for dapagliflozin in January 2012, and Eli Lilly & Co./Boehringer Ingelheim GMBH expect an approval decision on empagliflozin later this year.

Bristol and AstraZeneca’s dapagliflozin had been the front runner in the category until an FDA panel highlighted safety risks regarding liver toxicities and bladder malignancies, as well as doubts about efficacy in certain populations. Bristol told investors on an Oct. 24 call that it believes it can now satisfy FDA requirements with data from extension studies, and the companies are expected to resubmit the drug mid-year Also see "Bristol Signals Dapaglifozin’s Back On Track, Plans FDA Resubmission" - Pink Sheet, 24 October, 2012..

Meanwhile, Lilly and Boehringer submitted the NDA for empagliflozin on March 25, and an application has also been submitted in the EU. A Phase III program of the drug that includes 14,500 patients is currently ongoing; data from the late-stage studies is expected in late-2013, as well as 2014 Also see "Lilly/BI Report Success For Oral Diabetes Drug, Adjust Alliance" - Pink Sheet, 7 January, 2013..

J&J’s Janssen Pharmaceuticals division licensed exclusive rights to canagliflozin in 2009 from Mitsubishi Tanabe forNorth America, South America, Europe, the Middle East, Africa, Australia, New Zealand and parts of Asia. Janssen submitted a marketing authorization application for the drug in Europe in June 2012, but has not yet received a decision.

SGLT-2 inhibitors are just one class of diabetes treatments being pursued by Big Pharma. FDA is expected to assess four major categories of diabetes treatments this year, including SGLT-2 inhibitors, glucagon-like peptide 1 (GLP-1) agonists, dipeptidyl peptidase IV (DDP-4) inhibitors, and long-acting basal insulins Also see "2013 Diabetes NMEs Span Classes, But Safety Is A Review Issue For All" - Pink Sheet, 28 January, 2013.. While these products all use different mechanisms of action, they all address maintenance of the chronic disease that affects more than 25 million Americans and an estimated 370 million people worldwide, according to the companies.

J&J Gains FDA OK For First-In-Class Type 2 Diabetes Drug Invokana

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