Research and development update
Q1 result - 30 April 2009
Diabetes Care
In Europe, the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMEA) on 23 April adopted a positive opinion for Victoza® for the treatment of type 2 diabetes. Victoza® is the first once-daily human Glucagon-Like Peptide-1 (GLP-1) analogue developed for the treatment of type 2 diabetes. The positive opinion for Victoza® covers the expected indications of: combination treatment with metformin or a sulphonylurea in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea and combination treatment with metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy. Novo Nordisk expects to receive the European Marketing Authorisation from the European Commission within approximately two months.
The regulatory process for liraglutide in Japan is progressing according to plans and a decision by the Japanese regulatory authorities is expected in 2010.
On 2 April and as previously communicated, the Endocrinologic and Metabolic Drug Advisory Committee of the United States Food and Drug Administration (FDA) discussed questions related to liraglutide, Novo Nordisk’s once-daily human GLP-1 analogue which was filed for regulatory approval in the US in May 2008. The Advisory Committee voted on four questions related to the risk profile of liraglutide. A majority of Advisory Committee members supported that appropriate evidence of cardiovascular safety had been provided to rule out excess cardiovascular risk of liraglutide relative to comparators. Novo Nordisk has committed to do a large post-approval cardiovascular outcome study.
A majority of Advisory Committee members voted no to the question on whether the data available with the regulatory submission on thyroid C-cell tumours showed that this finding is not relevant to humans. However, the Advisory Committee was split on the FDA question related to whether the available data on C-cell tumours permitted approvability. Finally, the Advisory Committee unanimously dismissed any risk of papillary thyroid cancer related to liraglutide. Following the meeting, Novo Nordisk will be discussing next steps with the FDA to resolve the issues raised at the Advisory Committee meeting. US approval of liraglutide, and the timing thereof, will depend on the completion of the FDA's review of the application.
Novo Nordisk recently obtained two-year data from the liraglutide plus metformin combination study (LEAD™ 2). On a background of metformin therapy three different doses of liraglutide were compared to glimepiride treatment and placebo in people with type 2 diabetes. In total 880 people with diabetes completed the initial first six months of the study and 529 completed two years. People treated with liraglutide achieved statistically significant reductions in HbA1c compared to placebo after two years. Furthermore, significantly more people treated with the highest dose of liraglutide were below 7% HbA1c, the American Diabetes Association (ADA) target for good glycaemic control, compared to treatment with glimepiride. Finally, the favourable benefit to risk profile of liraglutide was confirmed in this study.
At the annual meeting of the American Diabetes Association (ADA) to be held in New Orleans on 5–9 June 2009, Novo Nordisk expects to present further detailed results from the global liraglutide clinical development programme.
Novo Nordisk very recently finalised a phase 2 study investigating safety and efficacy of five doses of semaglutide (NN9535), a once-weekly human GLP-1 analogue, versus placebo and open-label liraglutide add-on therapy in people with type 2 diabetes. At study start, patients were treated with metformin or controlled with diet and exercise. The 12-week multi-centre, multinational, double-blind, placebo-controlled, randomised dose-finding trial, which included a little more than 400 patients, demonstrated that clinical efficacy and safety of semaglutide was broadly in line with liraglutide. Semaglutide was generally well tolerated and was not associated with an increase in injection site reactions, antibody formation or calcitonin levels. After more detailed analysis of the dose-response findings on efficacy and safety, Novo Nordisk will discuss the future plans for semaglutide development with regulatory authorities before initiation of phase 3 development.
Novo Nordisk is preparing initiation of phase 3 programmes for the new generation of insulins, known as NN5401 and NN1250, in the second half of 2009 and good progress has been made with regulatory agencies around the world. The first phase 3 trials with NN1250 and NN5401 are expected to be initiated in the third and fourth quarters of 2009, respectively. Novo Nordisk expects to give a more detailed update on expected timelines and design of the phase 3 programmes in connection with the release of financial results for the first half of 2009 on 6 August 2009.
Biopharmaceuticals
In April 2009, Novo Nordisk initiated a phase 3 trial of a recombinant factor VIII compound in patients with haemophilia A. The trial is conducted as a multi-centre, open-label, noncontrolled trial and evaluates the efficacy and safety in both prevention and on-demand treatment of haemophilia A bleeding episodes. A sub-trial investigates efficacy and safety of the recombinant factor VIII compound in patients undergoing major or minor elective surgery requiring factor VIII replenishment. Novo Nordisk expects to enrol a total of 140 patients in the phase 3 programme.
Novo Nordisk recently received approval from the Japanese Pharmaceuticals and Medical Devices Agency for an expansion of the Norditropin® label to include treatment of growth hormone deficiency in adults. Growth hormone deficiency in adults is an approved indication for Norditropin® in both Europe and the US.
As previously communicated, Novo Nordisk initiated a phase 3 study with recombinant FXIII in congenital factor XIII deficiency in August 2008. All 41 patients have now been recruited and entered into the one-year treatment period of this trial.
