Novo Nordisk and Ionis Pharmaceuticals unveiled promising respective data at the American College of Cardiology’s Annual Scientific Session, while Boehringer Ingelheim and Eli Lilly’s Jardiance missed the endpoint in a myocardial infarction study.
The American College of Cardiology’s 73rd Annual Scientific Session & Expo (ACC24) took place over the weekend in Atlanta, spotlighting the latest and most impactful innovations in the field of cardiovascular care.
BioSpace has highlighted below some of the most notable presentations from ACC’s Annual Scientific Session.
Novo Builds Wegovy’s Cardio Case, Eyes Heart Failure
Still riding high from winning its recent cardiovascular approval for Wegovy (semaglutide), Novo Nordisk is continuing its expansion into heart health with new promising data from its Phase III STEP-HFpEF study.
At 52 weeks, patients treated with the blockbuster obesity drug saw a significantly greater reduction in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) versus placebo. Wegovy also outperformed the placebo group in terms of body weight reduction, six-minute walk distance and C-reactive protein levels.
Taken together, these findings suggest that Wegovy could significantly ease symptomatic burden and physical limitations in patients with obesity, heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus. The GLP-1 treatment also boosted patients’ exercise function and weight loss.
Results from the large Phase III trial, which randomized more than 600 patients, were also published on Friday in The New England Journal of Medicine.
Novo previously posted heart failure findings for Wegovy, announcing in August 2023 that the weight-loss medication could significantly improve KCCQ-CSS scores in the Phase III STEP trial, which enrolled patients with obesity and HFpEF, but not diabetes.
Novo has submitted data from these two studies to the FDA, seeking to expand Wegovy’s label to include HFpEF, STAT News reported.
Ionis Moves Toward Rare Metabolic Disorder Approval
Ionis Pharmaceuticals unveiled promising results from its Phase III BALANCE study at ACC24, showing that its investigational RNA-targeted antisense therapy olezarsen can reduce triglyceride levels in patients with familial chylomicronemia syndrome (FCS).
At six months, patients treated with the 80-mg dose of olezarsen saw a 44% placebo-adjusted reduction in triglyceride levels, an effect that was statistically significant, with a p-value less than 0.001, according to Ionis. This effect continued and improved through 12 months, reaching a 59% placebo-adjusted reduction.
Patients in the olezarsen arm also developed “markedly fewer” acute pancreatitis events over 12 months of follow-up.
CEO Brett Monia in a statement said that these results from BALANCE support “the potential for olezarsen to be the standard of care for patients with FCS, if approved,” adding that the company is “working closely with the FDA” for olezarsen’s regulatory application, which Ionis expects to file later this year.
Ionis in September 2023 revealed early data from BALANCE. At the time, olezarsen elicited a 100% reduction in acute pancreatitis events versus placebo.
Olezarsen is an RNA-targeted ligand-conjugated antisense treatment that works by lowering the body’s production of the apoC-III protein, which is produced in the liver and is involved in the regulation of triglycerides in the blood. Aside from FCS, Ionis is also studying the candidate in severe hypertriglyceridemia.
Boehringer, Lilly’s Jardiance Misses in Myocardial Infarction
Data from Boehringer Ingelheim and Eli Lilly’s Phase III EMPACT-MI trial showed that their SGLT2 inhibitor Jardiance (empagliflozin) does not significantly reduce the risk of heart failure hospitalization or death from any cause in patients who had suffered an acute myocardial infarction (MI) episode.
At a median follow-up of 17.9 months, 267 patients in the Jardiance arm developed the composite primary endpoint of being hospitalized for heart failure or dying from any cause. This figure corresponds to a rate of 8.2%, whereas the primary outcome arose in 9.1% of those patients in the placebo arm.
The between-group difference did not reach statistical significance, with a p-value of 0.21, according to the ACC’s news release on the results.
However, disaggregating the primary endpoint into its components showed that Jardiance could significantly lower the risk of a first hospitalization for heart failure by around 23% versus placebo.
EMPACT-MI lead author Javed Butler in a statement said that Jardiance “did not reduce mortality after a heart attack, but did reduce the risk of heart failure after heart attack,” adding that this “25% to 30% reduction” in heart failure hospitalizations is “pretty clinically meaningful.”
Jardiance also failed to elicit significant improvements in EMPACT-MI’s key secondary endpoints. An exploratory analysis also found no benefit on cardiovascular death, time to death from cardiovascular causes, as well as time to first heart failure hospitalization or cardiovascular death.
Arrowhead Shoots for Pivotal SHTG Study for Candidate
Arrowhead Pharmaceuticals unveiled Phase IIb data for its investigational RNAi therapy plozasiran at ACC24, demonstrating steep triglyceride reductions at 24 weeks in patients with severely elevated triglyceride levels who are at risk of developing acute pancreatitis.
In the mid-stage SHASTA-2 trial, Arrowhead’s asset reduced triglyceride levels by 74% while placebo only elicited a 17% decrease. Plozasiran also met the study’s key secondary endpoint, with its highest doses triggering a 58% average drop in triglyceride at 48 weeks versus 7% in the placebo group.
ApoC3, a liver protein that disrupts the clearance of fats from the body, was lowered by 48% among plozasiran-treated patient at 48 weeks. Placebo comparators, meanwhile, saw a 4% increase in ApoC3 at this time point.
SHASTA-2 lead author Daniel Gaudet said in a statement that these findings “support the initiation of pivotal studies of plozasiran for the treatment of severe hypertriglyceridemia.”
Plozasiran is an investigational RNAi therapeutic that works by interrupting the expression of the ApoC3 gene, resulting in overall lower levels of the protein. This mechanism of action could block the pathologic function of ApoC3 and help normalize lipid levels in patients, according to Arrowhead’s website.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
