Research and development update
Q3 result - 29 October 2009
Diabetes Care
Novo Nordisk continues the constructive dialogue with the United States Food and Drug Administration (FDA) regarding the regulatory process for liraglutide. Formal feedback from the FDA regarding liraglutide, a once-daily human GLP-1 analogue, is still expected in the fourth quarter of 2009.
At the annual meeting of the European Association for the Study of Diabetes (EASD) held in Vienna, Austria, from 30 September to 2 October this year, Novo Nordisk presented results from a new meta-analysis on the safety of Novo Nordisk’s long-acting modern insulin Levemir®. The meta-analysis assessed the relative risk of a cancer diagnosis during clinical treatment with Levemir®. It covered a total of approximately 9,000 patients in 21 randomised, controlled trials and compared the incidence of cancer in patients treated with Levemir® to that of patients treated with either human insulin (NPH insulin) or insulin glargine. The studies comparing Levemir® to NPH insulin revealed that treatment with Levemir® was associated with a statistically significant lower incidence of cancer than with NPH insulin treatment (0.36 events per 100 patient years in the Levemir® group versus 0.92 events in the NPH insulin group; p<0.05). The meta-analysis has recently been published online in Diabetologia, the journal of the EASD.
During the annual meeting of the EASD, Novo Nordisk also presented new experimental studies on the molecular safety of Levemir® and other insulins. These studies assessed comparative IGF-1 and insulin receptor subtype binding, as well as the potential of the insulins to induce cell growth (mitogenicity). Regarding the balance between insulin receptor and IGF-1 receptor binding, Levemir® was found to possess a profile very similar to that of human insulin, and when mitogenicity was studied in a number of different cell lines, it was found that Levemir® exhibited a similar or lower mitogenicity than human insulin.
The new generation of insulins, SIBA and SIAC, have now both entered phase 3 clinical development with the trial programmes named BEGIN™ and BOOST™, respectively. The large trial programmes with around 10,000 patients in total are executed in a sequence of four waves. The first wave for both programmes has been initiated and the first trials have completed recruitment; the second wave is expected to be initiated during the fourth quarter of 2009. In the BEGIN™ programme the second wave consists of one trial comparing the use of SIBA once daily in two different regimens to insulin glargine once daily in insulin naïve type 2 diabetes patients. In the BOOST™ programme, the trial in the second wave will investigate intensified use of SIAC compared to treatment with NovoMix® 30 in people with type 2 diabetes previously treated with premixed insulin. The final two waves are expected to be initiated during the first half of 2010.
In Japan, NovoRapid Mix® 50 and NovoRapid Mix® 70 have recently been approved by the Ministry of Health, Labor and Welfare. Both products have been approved for the treatment of adult type 1 and type 2 diabetes patients. Novo Nordisk expects to launch both NovoRapid Mix® 50 and NovoRapid Mix® 70 in 2010 in Japan when reimbursement discussions are finalised.
The results of the ‘Treating to Target in Type 2 Diabetes’ (4-T) study conducted by the Diabetes Trials Unit at the Oxford Centre for Diabetes, Endocrinology and Metabolism were recently published in the New England Journal of Medicine. The study, which was supported by Novo Nordisk and Diabetes UK, was a three-year randomised, controlled, multicentre trial, in which 708 patients with suboptimal HbA1c levels on metformin and sulphonylurea therapy were assigned to receive NovoMix® 30 (biphasic insulin aspart) twice daily, mealtime NovoRapid® (insulin aspart) three times daily, or Levemir® (insulin detemir) once daily. Among the outcome measures after three years were mean HbA1c, the proportion of patients with an HbA1c level of 7% or less, the rate of hypoglycaemia and weight gain.
The design of the 4-T trial made it possible to report differences between three different initiation and intensification regimens, all with insulin analogues, over the longest
randomised ‘treat-to-target’ comparison of insulin therapies yet published. The 4-T study showed that at three years, the mean HbA1c level did not differ between groups.The proportion of patients achieving an HbA1c level of 7% or less was high, and similar in the NovoRapid® (67%) and Levemir® (63%) initiation groups, but somewhat lower in the NovoMix® (51%) group. In the NovoMix® group, however, fewer patients received intensification with a second insulin preparation during the three-year treatment period. The median numbers of hypoglycaemic events per patient per year were relatively low, but highest for the NovoRapid® initiation group: 1.7 for the Levemir®, 3.0 for NovoMix® and 5.5 for NovoRapid® initiation groups, and the mean weight gains were 3.6 kg, 5.7 kg and 6.4 kg respectively. Thus, the group initiated on once-daily Levemir® therapy statistically significantly experienced the lowest weight gain despite being intensified to a basal bolus therapy with NovoRapid®. More than 80% of randomised patients completed the three-year trial during which the rates of adverse events were similar among all groups. Overall, the 4-T study in type 2 diabetes has shown that initiation of insulin treatment with once-daily Levemir® or twice-daily NovoMix® 30, followed by intensification with NovoRapid® when needed, is welltolerated and associated with similar, strong HbA1c lowering, in the presence of low levels of hypoglycaemia.
Biopharmaceuticals
In the area of haemophilia, and in line with previous communication, Novo Nordisk hasinitiated a phase 1 study with a long-acting rFIX derivative, a phase 1 study with a long-acting rFVIIa derivative for subcutaneous administration as well as a phase 2 study with a long-acting rFVIIa derivative for intravenous administration.
Novo Nordisk now expects to complete the ongoing phase 2 trial with NN1731 in the second quarter of 2010. NN1731 is a rFVIIa analogue designed to provide faster and more efficient haemostasis in haemophilia patients with inhibitors. The extended duration of the trial is due to a lower than anticipated number of bleeding events.
Novo Nordisk officially opened the new inflammation research centre based in Seattle, Washington, USA, in September this year. The research centre will leverage Novo Nordisk’s strong knowledge within the field of proteins in order to further build the company’s clinical pipeline of products for the treatment of chronic inflammatory diseases.
