Research and development update
Q3 result - 30 October 2008
Diabetes Care
Novo Nordisk is the only company with a new generation of insulins in full clinical development. The ambition is to further improve the treatment success rate, tolerability and convenience of insulin therapy for people with type 1 or type 2 diabetes. Novo Nordisk has made significant progress in this area and has recently finalised two phase 2 studies with NN1250, a long-acting insulin analogue with a potential duration of action of more than 24 hours, and two phase 2 studies with NN5401, a neutral, soluble dual-acting insulin analogue preparation also with a potential duration of action of more than 24 hours. NN1250 was investigated in both type 1 and type 2 diabetes, whereas NN5401 was investigated in type 2 diabetes alone. NN1250 was studied in trials where insulin glargine served as insulin comparator whereas NN5401 was studied in trials where NovoMix® 30 and insulin glargine served as insulin comparators. In total, around 700 patients were enrolled in the four treat-totarget studies and all patients were treated for 16 weeks.
The headline data from the four studies show promising proof-of-concept results for both of the new insulins in terms of safe and long-lasting blood glucose lowering. Between half and two-thirds of people with type 2 diabetes treated with NN5401 achieved HbA1c levels below 7% with no incidences of hypoglycaemia during the last four weeks of treatment. For people with type 2 diabetes treated with once-daily NN1250, around half achieved HbA1c levels below 7% without occurrence of hypoglycaemia in the last four weeks of treatment. In the type 2 diabetes trial three weekly injections of NN1250, every Monday, Wednesday and Friday, were also compared to once-daily basal insulin. The blood glucose control achieved after three weekly NN1250 injections was found to be similar to that in the once-daily basal insulin arm, highlighting the very long action profile of NN1250.
Importantly, both insulins, NN5401 and NN1250, appear to be safe and well tolerated. Based on the positive phase 2 data, Novo Nordisk will now start a dialogue with the regulatory agencies regarding the design of the phase 3 programmes. Novo Nordisk plans to initiate phase 3 studies with both NN1250 and NN5401 in the second half of 2009.
At the annual meeting of the Canadian Diabetes Association in October, Novo Nordisk presented detailed results from the 26-week LEAD™ 6 phase 3b study in which the safety and efficacy of liraglutide, the once-daily human GLP-1 analogue, was compared to twice-daily exenatide in people with type 2 diabetes. As previously communicated, the study showed that patients treated with liraglutide achieved a statistically significantly better blood glucose control, compared to patients receiving exenatide treatment.
At its Capital Markets Day on 26 September, Novo Nordisk presented headline data from a 14-week extension of the LEAD™ 6 study. After an initial 26 weeks of treatment with either liraglutide or exenatide in the LEAD™ study, 376 patients with type 2 diabetes entered this 14-week non-randomised extension study where all patients received liraglutide. Patients from the initial liraglutide treatment arm continued previous treatment at an unchanged dose while patients from the initial exenatide treatment arm were switched to liraglutide 1.8 mg once daily, following a two-week dose escalation period. The study showed that patients who switched from exenatide to liraglutide experienced a reduction in HbA1c of 0.3 percentage points, a decrease in fasting plasma glucose of 0.9 mmol/l, a weight loss of approximately 1 kg as well as a reduction in systolic blood pressure of close to 4 mmHg – all differences being statistically significant. Furthermore, the tolerability profile of liraglutide was confirmed in the LEAD™ 6 extension.
As previously communicated, the phase 3 programme for liraglutide in obesity is expected to be initiated before the end of 2008 and will include 4,500–5,000 patients. One-year data from the study is expected in early 2011.
Biopharmaceuticals
Novo Nordisk has decided to discontinue the phase 3 study with Norditropin® in dialysis patients with low serum albumin (LSAD) which was started in July 2007. The decision to discontinue the study is not due to safety concerns. The discontinuation is based on an analysis of the significant delay in recruitment of patients for the study which is expected to have a negative impact on the outcome of the study. The analysis shows that the study is not expected to be completed before 2012 or potentially later and that actions undertaken to accelerate patient recruitment have not been sufficiently successful. The primary endpoint in the study is mortality and the plan was to enrol around 2,500 patients.
Novo Nordisk regrets the inconvenience this may cause to patients, doctors and medical staff, and is grateful to all who took part in the study. Novo Nordisk will do its utmost to ensure a smooth trial closure for the involved patients and clinical centres. In the study, growth hormone or placebo treatment has been added in addition to existing treatment, not as a replacement for another treatment. Novo Nordisk expects to finalise the discontinuation of the study during the first half of 2009.
Novo Nordisk is finalising the analysis of results from the phase 3 trial with NovoSeven® for the treatment of bleeding in patients with severe trauma. As previously announced the trial was discontinued earlier this year based on the results of an analysis for futility conducted by the independent Data Monitoring Committee. In total 541 patients with severe trauma completed the trial. The primary efficacy endpoint was 30-day mortality and the results show that there was no statistical difference between the mortality outcome for patients treated with NovoSeven® and placebo. As seen in previous trials with NovoSeven® in trauma, patients treated with NovoSeven® in this trial received statistically significantly fewer transfusions at 24 and 48 hours compared to placebo, thereby confirming its haemostatic effect. The safety profile of NovoSeven® was consistent with previous trials of NovoSeven® in critical bleeds. Novo Nordisk expects to publish detailed results from the phase 3 trial in peer-reviewed journals and at scientific conferences in 2009.
At the Capital Markets Day, Novo Nordisk provided an update of the haemostasis strategy including plans for extending activities into general haemophilia. This was underpinned by the announcement that phase 1 studies are expected to be initiated with a recombinant factor VIII compound and a long-acting recombinant factor IX compound during 2008 and 2009 respectively. Additionally, it was announced that the long-acting recombinant FVIIa derivative NN7128 has completed phase 1 and that a phase 2 study is expected to be initiated in 2009.
Within haemostasis Novo Nordisk also announced that the phase 3 study with recombinant FXIII in congenital factor XIII deficiency was initiated in August 2008. In addition, it was announced that a phase 2 study with recombinant factor XIII within prevention of bleeding in cardiac surgery is expected to be initiated in 2009.
Finally, at the Capital Markets Day, Novo Nordisk provided an update on the progress in the area of inflammation research and announced the progression of the first two projects, anti-IL-
20 and anti-C5aR, to phase 1 clinical development.
