European Commission approves VOKANAMET for treatment of adults with type 2 diabetes mellitus

Janssen-Cilag International NV (Janssen) announced today that the European Commission (EC) has approved VOKANAMET^® (a fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride in a single tablet) in the European Union, for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control. Canagliflozin as a single agent was approved as INVOKANA^® in the European Union in November 2013.

This EC decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending the approval of canagliflozin and immediate release metformin hydrochloride fixed dose combination therapy, in February 2014. The combination therapy, which is taken as a single pill twice daily, is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in:

• patients not adequately controlled on their maximally tolerated doses of metformin alone;
• patients on their maximally tolerated doses of metformin along with other glucose-lowering medicinal products including insulin, when these do not provide adequate glycaemic control;
• patients already being treated with the combination of canagliflozin and metformin as separate tablets;

Professor Guntram Schernthaner, Department of Medicine I, Rudolfstiftung Hospital, Austria comments, "The approval of VOKANAMET^® in the European Union is very welcome news for the growing number of people with type 2 diabetes in this region. Many patients struggle to achieve and maintain long-term glycaemic control, and the introduction of VOKANAMET^® provides added convenience to diabetes management, particularly to those patients who may benefit from two diabetes medications in one tablet."

Commenting on the approval, Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East, and Africa said, "We are delighted that the European Commission has approved VOKANAMET^® for use in the European Union, recognising the value and the convenience that this combined treatment option provides for patients. This approval further reinforces Janssen's ongoing commitment to provide new therapeutic options that help to address unmet needs in the treatment of type 2 diabetes."

The EC approval of this fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride in a single tablet taken twice daily was based on significant portions of the comprehensive global Phase 3 clinical development programme for canagliflozin single agent, including the studies with co-administration of metformin and canagliflozin as individual tablets.

The Phase 3 programme evaluated the safety and efficacy of canagliflozin across the spectrum of type 2 diabetes and included placebo and active comparator controlled studies. Three studies have compared canagliflozin to current standard treatments, two of which compared canagliflozin to sitagliptin as dual therapy with metformin and the other as triple therapy with metformin and sulphonylurea. In addition there is a study comparing canagliflozin to glimepiride as dual therapy with metformin. The Phase 3 programme also included two large studies in special populations: patients over age 55 with type 2 diabetes and patients with type 2 diabetes who were considered to be at high risk for cardiovascular disease.

Single agent canagliflozin (INVOKANA^®) was approved in the US in March 2013, and in the European Union, as well as Norway, Liechtenstein and Iceland in November 2013.

Canagliflozin is a member of a new class of drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors contribute to controlling blood glucose levels via the kidney. As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream. An important transport carrier in the renal proximal tubule responsible for this reabsorption is called sodium glucose co-transporter 2 (SGLT2). Canagliflozin selectively inhibits SGLT2, and, as a result, promotes the loss of glucose via the urine, lowering blood glucose levels in adults with type 2 diabetes. This mechanism of action is independent of insulin.

Metformin is a first-line pharmacotherapy that can be used alone or with other medications, including insulin, to treat type 2 diabetes. In people with type 2 diabetes, the liver overproduces glucose, which increases blood glucose levels. Metformin lowers blood glucose levels by decreasing the amount of glucose made by the liver, increasing insulin sensitivity in the muscle and delaying intestinal glucose absorption.

Janssen and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen and its affiliates have marketing rights in North America, South America, Europe, the Middle East, Africa, Australia, New Zealand and parts of Asia.