On June 20th, 2017, the Endocrinological and Metabolic Drugs Advisory Committee (EMDAC) discussed the supplemental new drug application (sNDA) 022341, for Novo Nordisk’s VICTOZA® (liraglutide injection) which outlined an additional indication for the product. The proposed additional indication for VICTOZA® was as an adjunct to standard treatment of cardiovascular (CV) risk factors to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes mellitus and high CV risk. MACE encompasses CV events such as, CV death, non-fatal myocardial infarction (MI or heart attack), or non-fatal stroke.
VICTOZA® is an approved non-insulin, once daily injection, which can help lower blood sugar levels in patients with type 2 diabetes. VICTOZA® is a form of the human metabolic hormone incretin glucagon-like peptide-1 (GLP-1). The binding of this hormone to a GLP-1 receptor in a healthy human stimulates insulin secretion. VICTOZA® acts in the same way, which lowers blood sugar without the need for exogenous insulin.
The sponsor, Novo Nordisk, presented CV outcome results from their Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results (LEADER®) study. The LEADER® study demonstrated superiority of VICTOZA® versus placebo for the reduction in MACE by a statistically significant 13%. In addition to VICTOZA®’s previously approved indication of improving glycemic control in adults with type 2 diabetes, the sponsor believed that the product should be considered for the CV risk reduction indication as well. The sponsor presentation to the FDA concluded with the demonstration of a favorable benefit-risk profile of VICTOZA®, noting that the product demonstrated reductions in MACE and all-cause mortality, as well as decreasing rates of hypoglycemia. The sponsor presentation was then followed by the FDA presentation, which was largely in favor of supporting the additional CV risk indication.
Following both the sponsor and FDA presentations, the panel was asked a series of discussion/voting questions. The first discussion question asked panel members to touch on if the data presented from the LEADER® study informs a causal relationship between VICTOZA® use and non-CV outcomes, such as medullary thyroid carcinoma, pancreatic neoplasm, and pancreatitis. Additional discussion focused on the design of the LEADER® study, which was largely supported by the panel members.
Lastly, two voting questions were posed to the committee. The first voting question was: “Do the results of LEADER establish that use of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) is not associated with unacceptably high cardiovascular risk?” Panel members voted unanimously positive, 19 yes to 0 no. Panel members agreed that there was no unacceptably high CV risk associated with VICTOZA®. The second voting question was: “Does the LEADER trial provide the substantial evidence needed to establish that liraglutide 1.8 mg daily reduces cardiovascular risk in patients with T2DM?” The vote was 17 yes to 2 no. The panel members who voted ‘no’ commented on their concern for utilizing single-trial data for new indications and that an additional international trial, where the United States subgroup is similar the rest of the world, or an additional US-based trial may be warranted
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