Results from two early studies published in NEJM could have important implications for patients with heart failure (HF) and reduced LVEF and for adults with heterozygous familial hypercholesterolemia (HFH) or premature coronary artery disease, respectively.

In an open-label phase 1-2 study, researchers found that cardiac remuscularization with stem-cell derived biologic ventricular assist tissue (BioVAT) was associated with increased target heart-wall thickness and LVEF, as well as improved Kansas City Cardiomyopathy Questionnaire–Overall Summary Scores (KCCQ-OSS), in patients with HF and LVEF of <35% and at least one hypokinetic or dyskinetic LV segment.

Researchers enrolled 20 patients in the study, each of whom received BioVAT allografts and immunosuppression treatment. Of the 20 patients, all experienced at least one adverse event and three died during the study. In addition, one patient underwent heart transplantation and four discontinued immunosuppression treatment.

All told, a total of 16 patients were treated with the safe maximal dose of BioVAT (20 engineered-heart-muscle units), with 12 completing three months of prespecified interim follow-up. Results showed a least-squares mean increase in target-wall thickness of 4.5 mm and an increase in LVEF of 3.9 percentage points. KCCQ-OSS increased by 6.7 points. Based on these results, the study authors led by Wolfram-Hubertus Zimmermann, MD, suggest that "longer-term follow-up and further clinical investigation are warranted."

In another open-label phase 1 study, researchers found that an investigational base-editing therapy called VERVE-102 that durably inactivates PCSK9 in the liver led to "dose-dependent, substantial and sustained reductions in PCSK9 and LDL cholesterol levels" in people with HFH or premature coronary artery disease.

Researchers administered one intravenous infusion of VERVE-102 at one of six doses (ranging from 0.3 to 1.0 mg of total RNA per kilogram of body weight) to 35 participants and followed up for a minimum of 28 days and up to one year. Overall results found dose-dependent mean reductions in PCSK9 levels ranged from 51% (0.3-mg-per-kilogram dose) to 88% (1.0-mg-per-kilogram dose). Corresponding reductions in LDL-C levels ranged from 9% (0.3-mg-per-kilogram dose) to 62% (1.0-mg-per-kilogram dose), with an absolute reduction of 78 mg per dL at the highest dose.

According to Scott B. Vafai, MD, et al., no dose-limiting toxic effects were observed. However, mild-to-moderate infusion-related reactions and transient elevations in alanine aminotransferase levels did occur. The reductions in PCSK9 and LDL-C levels "appeared to be durable throughout follow-up," they said.