Novo Nordisk submits application in the US for including data from the DEVOTE trial in the Tresiba® label

Bagsværd, Denmark, 27 May 2017 - Novo Nordisk today announced the submission of a supplemental application to the US Food and Drug Administration (FDA) for including data in the label for Tresiba^® (insulin degludec) from the DEVOTE trial, a long-term, randomised, double-blinded and event-driven trial conducted to confirm the cardiovascular safety of Tresiba^® compared to insulin glargine U100 when added to standard of care, in people with type 2 diabetes.

In the DEVOTE trial, the primary endpoint was achieved by demonstrating non-inferiority of major adverse cardiovascular events (MACE) with Tresiba^® compared to insulin glargine U100. The trial thereby confirmed the results of the DEVOTE interim analysis submitted to the FDA in March 2015, on the basis of which Tresiba^® and Ryzodeg^® 70/30 were approved in the US in September 2015.

The primary endpoint of the DEVOTE study was defined as the MACE composite outcome of the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke and showed a hazard ratio of 0.91 in favour of Tresiba^® relative to insulin glargine U100, with no statistically significant difference between the two treatments.

From a mean HbA_1c baseline of 8.4%, the trial showed a similar reduction with Tresiba^® compared to insulin glargine U100 with an end-of-trial treatment difference of 0.01 percentage points between the two treatment arms, thus fulfilling the requirements for objectively comparing hypoglycaemia rates between the two treatments.

In the trial, Tresiba^® demonstrated superiority on the secondary confirmatory endpoint of severe hypoglycaemia: 27% fewer patients in the Tresiba^® treated group experienced an episode of severe hypoglycaemia, resulting in a 40% overall rate reduction of total episodes of adjudicated severe hypoglycaemia. Furthermore, patients in the Tresiba^® treated group experienced a 54% relative reduction in the rate of nocturnal severe hypoglycaemia. These differences were all statistically significant.

Tresiba^® appeared to have a safe and well-tolerated profile consistent with previous clinical studies conducted with Tresiba^®.

"The risk of severe hypoglycaemia is a major cause for people with type 2 diabetes not reaching their treatment targets," said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. "However, with the DEVOTE data, we have demonstrated that the strong clinical profile of Tresiba^® leads to a significant reduction in severe hypoglycaemia in people with type 2 diabetes."

About DEVOTE

DEVOTE is a long-term, multi-centre, multi-national, randomised, double-blinded, parallel group and event-driven trial conducted to confirm the cardiovascular safety of Tresiba^® (insulin degludec) compared to insulin glargine U100. In the trial, 7,637 people with type 2 diabetes at high risk of cardiovascular disease were randomised to treatment with either Tresiba^® or insulin glargine U100 in vial in addition to standard of care.

The DEVOTE trial has been conducted in response to a Complete Response Letter received from the FDA in February 2013 requesting additional cardiovascular data from a dedicated cardiovascular outcomes trial before the review of the New Drug Applications for Tresiba^® and Ryzodeg^® 70/30 could be concluded. Tresiba^® and Ryzodeg^® 70/30 were approved in the US in September 2015 on the basis of an interim analysis of DEVOTE.