Phase III data for Omecamtiv Mecarbil and Finerenone demonstrates reduced risk of cardiovascular events at AHA conference

A record number of late-breaking trials were submitted to the Annual Scientific Sessions of the American Heart Association (AHA) this year and unsurprisingly, a key theme of this year’s conference was the COVID-19 pandemic, says GlobalData, a leading data and analytics company.

Fiona Chisholm, Managing Analyst at GlobalData, comments: “One notable study, which analyzed records from 28,299 patients hospitalized for COVID-19 infection in the US up until July 1, 2020, identified an increased risk of death among patients with pre-existing cardiovascular (CV) disease. The outlook was particularly poor for patients who experienced in-hospital CV events. Mortality rates among patients who experienced a stroke, myocardial infarction, or pulmonary embolism were 56%, 55.5%, and 26.5%, respectively.”

CV disease is highly prevalent in the US population. GlobalData estimates that the diagnosed prevalence of hypertension alone is approximately 61 million cases. Combined with the high rate of hospitalization for COVID-19 infection in the country, this translates into an extremely high risk of death for a large proportion of the US population.

Chisholm comments: “As Pfizer/BioNTech, Moderna and Oxford University/AstraZeneca have recently announced that interim analyses of their respective Phase III COVID-19 vaccines have succeeded efficacy expectations, the prospect of a vaccine roll-out in the near-future seems much more likely, sparking debate about which patients should be prioritized first. The results of this study support prioritization for CV disease patients, particularly those with other risk factors, such as advanced age.”

Beyond COVID-19, there were several updates on clinical trial data for high-profile late-stage drug candidates. The GALACTIC-HF trial investigated the effects of Amgen’s cardiac myosin activator omecamtiv mecarbil (OM), in patients with heart failure with reduced ejection fraction (HFrEF). The study met its primary endpoint, demonstrating a significant 8% reduction in the risk of the composite outcome of time to first heart failure event or CV death in patients treated with OM relative to placebo.

However, GALACTIC-HF’s findings still fall short of industry expectations. When considered in isolation, neither of the components of the primary composite endpoint—risk of first heart failure event and risk of CV death—were significantly different between the OM and placebo groups.

Chisholm continues: “This raises questions about OM’s practice-changing potential, particularly in the context of an increasingly crowded market landscape. If OM is approved, Amgen could target it to patients with more severely reduced systolic function. Interestingly, the subgroup of patients with an ejection fraction less than or equal to 28% were found to derive the greatest benefit from the therapy.”

Bayer’s finerenone – a mineralocorticoid receptor antagonist – was investigated in patients with type 2 diabetes (T2D) co-morbid with chronic kidney disease (CKD) in the FIDELIO-DKD trial. Finerenone was associated with a significant 14% reduction in the risk of CV events compared to placebo.

Chisholm adds: “In recent years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors have demonstrated clinical benefit in both T2D and CKD patient populations. However, there is still a need for more therapeutic options. The results of this study indicate that finerenone could provide patients with an important new treatment option.”

There were also some studies with surprising results. In particular, the STRENGTH and OMEMI trials failed to demonstrate any benefit of omega-3 fatty acid (FA) administration in terms of reduced risk of cardiovascular events, relative to placebo. STRENGTH enrolled statin-treated patients who had, or were at high risk for CV disease while OMEMI recruited elderly patients (ages 70–82 years) who had recently experienced a myocardial infarction. The data from these studies contradict the findings of the recent REDUCE-IT trial, which reported a significant risk reduction in CV events among omega-3 FA-treated patients relative to placebo. The exact reasons for this are unclear but it may reflect differences in the omega-3 FA preparations and placebo comparators chosen in the studies.

Chisholm concludes: “Further research, such as a head-to-head trial of Epanova  (omega-3-carboxylic acids) versus Vascepa (icosapent ethyl)  (the preparations used the STRENGTH and REDUCE-IT trials, respectively), using corn oil as a placebo comparator (which was used in the STRENGTH and OMEMI trials but not the REDUCE-IT trial), may help to elucidate some of these contradictions.”

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