Heart Disease Therapies Pack a Punch with Promising Study Results
Three companies have posted major developments in the field of heart disease therapy.
AstraZeneca, Moderna AZD8601 Drug Trial Meets Primary Endpoint
In the Phase IIA EPICCURE trial, scientists injected AZD8601, an mRNA encoding vascular endothelial growth factor (VEGF-A), into the myocardium of patients undergoing elective coronary artery bypass (CABG) surgery. VEGF-A is a paracrine factor that's essential to the creation of blood vessels. It works by stimulating the division of progenitor cells, which contribute to heart repair and regeneration.
Out of 11 patients, seven were given AZD8601, while the remaining four were given a placebo. The participants were then observed for six months according to three efficacy endpoints, namely the NT-proBNP, a high biomarker in patients with heart failure, left ventricular ejection fraction (LVEF), and patient reported outcomes.
After six months, no infections, treatment-related serious adverse events, or deaths were reported. Given the size of the trial, the data is not enough to make any conclusions about the drug, but it opens up opportunities to conduct more comprehensive studies on its effectiveness in the future.
"mRNA is a compelling therapeutic modality because of its ability to act locally and transiently, while driving dose-dependent protein expression. The results presented today are a result of pushing new boundaries in the treatment of cardiovascular and other ischemic vascular diseases and address serious unmet needs with the goal of improving patients' lives," commented Stéphane Bancel, the chief executive of Moderna, in a statement.
Heart failure is a chronic illness that affects some 64 million people worldwide, including six million in the U.S. The prognosis is not good as half of the patients are likely to die within five years. It is said to be as deadly as breast cancer in women and bladder and prostate cancers in men. Chronic heart failure is the leading cause of hospitalization in 65 years and older, creating a significant problem clinically and financially.
"Over one billion heart cells can be lost during a heart attack. These early results indicate the potential of mRNA therapeutics in stimulating VEGF-A production to provide reparative and disease-modifying options for patients with heart failure and other ischemic vascular diseases," added Mene Pangalos, executive vice president for the biopharmaceuticals R&D arm of AstraZeneca.
AstraZeneca and Moderna signed an exclusive agreement to discover, develop, and commercialize mRNA therapies to treat serious metabolic, cardiovascular, and renal illnesses, as well as cancer. Details on the EPICCURE trial were presented at the American Heart Association's Scientific Sessions on November 15.
Mesoblast's Rexlemestrocel-L Demonstrates Benefit in the Treatment of CHF-HFrEF
In other news, Mesoblast Limited announced positive results from its Phase III landmark trial of rexlemestrocel-L in the treatment of patients with New York Heart Association (NYHA) class II and class III chronic heart failure (CHF) with reduced ejection refraction (HFrEF).
New data confirmed a significant benefit after the drug was given to people with systemic inflammations, as measured by a high sensitivity of C-reactive proteins, and were at risk for heart attack, stroke, or cardiovascular mortality. Rexlemestrocel-L works by reducing the inflammatory cytokine production of immune cells, which in turn lowers the risk for plaque rupture in key arteries.
One dose of rexlemestrocel-L, plus the standard of care (SoC), lowered the risk for stroke or heart attack by 65% across all 537 participants (both class II and III). In the 301 patients with high inflammation levels, the drug reduced risk by 79%.
Those who received one dose plus SoC saw their risk go down by 80% in terms of cardiovascular death. The addition of rexlemestrocel-L to the patients' regimen did not affect the frequency of hospitalization, however.
The study, which has been submitted for publication, was presented as a late-breaking presentation at the American Heart Association's annual Scientific Sessions. It was conducted by scientists from the Texas Heart Institute, co-led by Dr. Emerson Perin, the institute's medical director and a clinical professor at the Baylor College of Medicine.
Type 2 Diabetes Drug Shows Potential for Acute Heart Failure
In the same AHA event, researchers from the Netherlands presented good news in using a popular type 2 diabetes drug for the treatment of patients with acute heart failure.
In the study titled "Efficacy and Safety of Empagliflozin in Hospitalized Heart Failure Patients: Main Results from the EMPULSE Trial," University Medical Centre Groningen scientists demonstrated the clinical benefit of empagliflozin, an SGLT2 inhibitor, in treating adults whose conditions had already stabilized after being hospitalized for acute heart failure. The treatment addressed the low quality of life and the higher risk for rehospitalization or death after suffering from the illnesses.
Empagliflozin was tested on 530 adults aged an average of 68 years and had already been in the hospital for acute heart failure. The first group was given a 90-day regimen of 10 mg empagliflozin tablets to be taken once a day, while the second group received a 90-day supply of placebo drugs. Outcomes were evaluated using the 23-item self-administered Kansas City Cardiomyopathy Questionnaire, where the patients had to report an improvement of at least five points for the drug to be considered clinically beneficial.
After 90 days, the researchers found that those who took empagliflozin were 36% more likely to see a reduced risk for mortality and heart failure events. This is regardless of whether or not they did have type 2 diabetes. The proponents admit that the study sample is not large enough to make any conclusions for now, but this opens up many opportunities to further explore the potential of this diabetes drug to cross over to the treatment of heart disease.