Although liraglutide is associated with an increase in resting heart rate of 2-3 bpm compared to a placebo, a long-term CVOT of 9340 patients with T2D revealed that those assigned to liraglutide 1.8 mg had a lower MACE incidence compared to a placebo group after a median follow-up of 3.8 years (53).
At the time of approval in 2012, based on the observation of a slight increase in heart rate, especially in the first two months of treatment with phentermine/topiramate, the FDA required (62) that a postmarketing CVOT be conducted and completed by 2017; a review of clinical trials registry in June 2017 revealed that such a study has not been conducted.
The company added that it has since the approval of Ozempic (once-weekly injectable semaglutide), in August 2016, engaged in a constructive dialogue with the US FDA (Food and Drug Administration) on minimising the need for additional separate large cardiovascular outcomes trials (CVOTs
) to obtain a cardiovascular (CV) indication for semaglutide in different formulations
AstraZeneca announced results from the Phase III DECLARE-TIMI 58 cardiovascular outcomes trial for Farxiga, the broadest SGLT2 inhibitor CVOT
conducted to date.
As expected, the increase in research and development expenses was primarily related to clinical development costs for the bempedoic acid / ezetimibe combination pill and bempedoic acid, including costs to support the completion of three global pivotal Phase 3 studies during the period, the ongoing CLEAR CVOT
, and increases in our headcount and stock-based compensation expense.
- Anglo-Swedish biopharmaceutical company AstraZeneca (OTC: AZNCF) has received positive results from the Phase III DECLARE-TIMI 58 cardiovascular outcomes trial for Farxiga (dapagliflozin), the broadest SGLT-2 inhibitor CVOT
conducted to date, the company said.
21 September 2011 - US biopharmaceutical company Orexigen Therapeutics Inc (NASDAQ:OREX) said yesterday that following a recent meeting with senior officials in the US Food and Drug Administration (FDA), it had received written correspondence detailing design requirements for a cardiovascular (CV) outcomes trial (CVOT
) for Contrave that would address the Complete Response Letter (CRL) received in January 2011.
These applications for the oral semaglutide and Ozempic cardiovascular risk reduction indications are based on the results of two cardiovascular outcomes trials (CVOTs
) evaluating the effects of adding semaglutide or placebo to standard of care on the risk of cardiovascular events, PIONEER 6 with oral semaglutide and SUSTAIN 6 with Ozempic.
Current Situation: Cardiovascular Outcome Trials (Cvots
) on Glp-1 Receptor Agonists
Updates to the guidance took into consideration recent evidence from large CV outcome trials (CVOTs
), which included the CANVAS programme, the largest completed and published CV outcomes trial to date for an SGLT2i, which has shown that canagliflozin reduces the risk of major adverse cardiovascular events including CV mortality, non-fatal myocardial infarction or non-fatal stroke in patients with T2DM who had either a history of CV disease or at least two CV risk factors, as well as reducing hospitalisation for heart failure and demonstrating improved renal outcomes.
The panel reviewed nearly 500 published manuscripts (n=479), with a particular focus on key cardiovascular outcomes trials (CVOTs
) in the past four years, to provide guidance on optimizing blood glucose control, improving patient outcomes, and reducing the serious complications of type 2 diabetes including cardiovascular and chronic kidney disease.