Verve Therapeutics pauses enrollment in Heart-1 trial of VERVE-101

Verve Therapeutics announced updates from the Heart-1 Phase 1b clinical trial of VERVE-101 and clearance of its Clinical Trial Applications by the U.K. Medicines and Healthcare products Regulatory Agency and Health Canada for VERVE-102, with the Heart-2 Phase 1b clinical trial expected to initiate in the second quarter of this year. VERVE-101 is being evaluated in the Heart-1 Phase 1b clinical trial with trial endpoints of safety and tolerability as well as changes in blood PCSK9 protein and low-density lipoprotein cholesterol levels in patients living with heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease, and uncontrolled hypercholesterolemia. Six participants have been dosed at 0.45 mg/kg of VERVE-101, with a total of 13 participants dosed in the study. For the first five participants in the 0.45 mg/kg cohort with follow-up to at least 28 days, VERVE-101 demonstrated time-averaged LDL-C reductions ranging from 21% to 73%, and averaging 46%. In the two patients with the longest follow-up in the 0.45 mg/kg or 0.6 mg/kg cohorts, LDL-C lowering has been durable out to 270 days, with follow-up ongoing. However, the sixth participant treated in the 0.45 mg/kg cohort experienced a Grade 3 drug-induced transient increase in serum alanine aminotransferase as well as a serious adverse event of Grade 3 drug-induced thrombocytopenia within the first four days after dosing. In light of such observed laboratory abnormalities associated with VERVE-101, Verve, in consultation with the study’s independent data and safety monitoring board, has decided to pause enrollment in the Heart-1 clinical trial. Verve is conducting an investigation into the laboratory abnormalities and based on those results, expects to work with regulatory authorities to define a path forward for VERVE-101. These safety events were reported to the U.S. Food and Drug Administration, MHRA, and the New Zealand Medicines and Medical Devices Safety Authority (Medsafe). The VERVE-101 Investigational New Drug Application and other CTAs remain active. Verve is now prioritizing the development of VERVE-102 and the initiation of the Heart-2 clinical trial.