Verve Therapeutic Provides First Look At Gene-Editing Drug For Inherited High 'Bad' Cholesterol, Shares Fall

Verve Therapeutics Inc VERV released the first human proof-of-concept data for in vivo base editing from the ongoing heart-1 phase 1b trial of VERVE-101 from the first ten people treated.

The data were presented at the American Heart Association's annual meeting.

All ten were enrolled with heterozygous familial hypercholesterolemia (HeFH), an inherited condition that causes severe elevations in low-density lipoprotein (LDL) cholesterol. 

VERVE-101 is an investigational, in vivo base editing medicine designed to be a single-course treatment that inactivates the PCSK9 gene in the liver to durably lower blood LDL-C.

Among three participants given the two highest tested doses, treatment with Verve's therapy lowered LDL cholesterol levels by 39%, 48%, and 55% compared to the study's start. 

PCSK9 levels were also reduced by 59%, 84%, and 47%, respectively. 

The other participants, treated with two "sub-therapeutic" doses, had much lower reductions.

The heart-1 trial enrolls patients in the 0.45 mg/kg and 0.6 mg/kg cohorts in the U.K. and New Zealand. With the recent clearance of the IND application by the FDA for VERVE-101, Verve plans to activate and open U.S. sites. 

In 2024, the company plans to select a single dose from the dose escalation phase, initiate an expansion cohort, and complete this expansion cohort of the heart-1 clinical trial. 

In the first half of 2024, the company plans to initiate a phase 1 clinical trial of VERVE-102, subject to regulatory clearance. VERVE-102 is an in vivo base editing medicine that aims to inactivate the PCSK9 gene similarly to VERVE-101. 

After completing the heart-1 and VERVE-102 trials, Verve plans to initiate a randomized, placebo-controlled phase 2 clinical trial of either VERVE-101 or VERVE-102 in 2025.

Two patients experienced serious adverse events, which were each cardiovascular events in the context of severe underlying ASCVD. One patient dosed in the 0.3 mg/kg cohort had a fatal cardiac arrest approximately five weeks after treatment due to underlying ischemic heart disease, which was determined by the investigator and independent data and safety monitoring board to be not related to treatment.

Price Action: VERV shares are down 42.80% at $8.98 on the last check Monday.