EASD 2016: Novo Nordisk presents detailed results on semaglutide’s CV benefit.
By Kevin Shannon, Analyst
23 September 2016
I am an analyst at Datamonitor Healthcare, currently located in San Diego, California, where I am a member of the cardio...
Read full bio
Results from Novo Nordisk’s SUSTAIN-6 cardiovascular outcomes trial (CVOT), presented at the 52nd Annual Meeting of the European Association for the Study of Diabetes, demonstrated a significant reduction in major adverse cardiovascular events (MACE) with the company’s investigational glucagon-like peptide-1 (GLP-1) agonist, semaglutide. While data collected from the trial are unlikely to be sufficient to support the inclusion of a cardiovascular (CV) benefit on semaglutide’s label, these results are expected to strengthen Novo Nordisk’s New Drug Application (NDA) and support future negotiations with pricing regulators.
Semaglutide is the third antidiabetic, and the second GLP-1 agonist following Victoza (liraglutide; Novo Nordisk), to demonstrate a CV benefit. This gives it a significant advantage over other GLP-1 agonists which have failed to demonstrate such a benefit in their CVOTs. Semaglutide demonstrated a statistically significant 26% reduction in MACE during the two-year, 3,297-patient study (Marso et al., 2016). These results are impressive considering the SUSTAIN-6 trial was only powered to rule out an 80% increased risk of MACE versus placebo – the current pre-approval threshold set by the US Food and Drug Administration (FDA).
An analysis of the SUSTAIN-6 trial’s individual data endpoints highlights that the overall reduction in MACE was primarily driven by the statistically significant 39% reduction in non-fatal stroke observed in the treatment arm of the trial. Treatment with semaglutide also led to a non-significant 26% reduction in non-fatal myocardial infarction, and a neutral outcome on CV death (Marso et al., 2016). The lack of an observed reduction in CV death inevitably leads to questions about the comparability of the data to Victoza’s LEADER trial, which demonstrated a statistically significant 22% reduction in CV death (Novo Nordisk, 2016). However, the SUSTAIN-6 trial investigators are keen to point out that this difference may be due to normal variability between trials, or due to differences in trial duration.
While the positive data will certainly strengthen Novo Nordisk’s NDA for semaglutide, which is expected to be submitted to the FDA later this year, the company does not expect the results to be sufficient for semaglutide to gain the same expanded label the company is also currently seeking for Victoza. Novo Nordisk does, however, expect the SUSTAIN-6 data to be included in semaglutide’s prescribing information once the drug gains approval. This may allow Novo Nordisk to negotiate a better deal for semaglutide in discussions with pricing regulators. The company also expects to run a larger and longer CVOT for semaglutide post-approval, in order to fully investigate the potential outcomes associated with the drug. This may provide it with sufficient data to apply for a label expansion for semaglutide, and will also allow the company to target patient populations that can expect the greatest benefit from the positive CV effects.
Marso S, Bain S, Consoli A, Eliaschewitz F, Jodar E, et al. (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine <DOI>10.1056/NEJMoa1607141</DOI>.
Novo Nordisk (2016) Victoza® (liraglutide) significantly reduced the risk of major cardiovascular events and death in adults with type 2 diabetes in the LEADER trial. Available from: http://press.novonordisk-us.com/News-Releases?item=122866 [Accessed 19 September 2016].
Get your free demo of Datamonitor Healthcare today. Simply fill out the form to the right >>>