Verve Therapeutics Announces Updates on its PCSK9 Program - Seite 2

In light of such observed laboratory abnormalities associated with VERVE-101, Verve, in consultation with the study’s independent data and safety monitoring board (DSMB), 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 (FDA), MHRA, and the New Zealand Medicines and Medical Devices Safety Authority (Medsafe). The VERVE-101 Investigational New Drug Application (IND) and other CTAs remain active.

Verve is now prioritizing the development of VERVE-102 and the initiation of the Heart-2 clinical trial. VERVE-102 uses the same base editor and guide RNA for PCSK9 but a different lipid nanoparticle (LNP) delivery system than VERVE-101. VERVE-102 has two principal differences from VERVE-101. First, VERVE-102 includes a different ionizable lipid from VERVE-101. VERVE-102’s ionizable lipid has already been used in third-party clinical trials of gene editing product candidates and has been well-tolerated in these trials. Second, the incorporation of GalNAc allows the LNP in VERVE-102 to access liver cells using either the asialoglycoprotein receptor (ASGPR) or the low-density lipoprotein receptor (LDLR). Verve has received regulatory clearances for the Heart-2 clinical trial in the U.K. and Canada and plans to initiate the Heart-2 clinical trial in patients with HeFH or premature coronary artery disease in the second quarter of 2024.

“The Heart-1 clinical trial continues to support proof-of-concept for in vivo base editing of the PCSK9 gene in the liver, with a meaningful and durable lowering of LDL-C,” said Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve. “However, at potentially therapeutic dose levels of VERVE-101, we have observed certain asymptomatic laboratory abnormalities, which we believe are attributable to the LNP delivery system. The safety of patients in our clinical trials is of the utmost importance. We plan to further investigate the laboratory abnormalities observed in the Heart-1 clinical trial in order to inform the next steps for VERVE-101. At this time, we are prioritizing the initiation of the Heart-2 clinical trial of VERVE-102 due to its proximity to the clinic and its use of a different LNP that incorporates an ionizable lipid which has been well-tolerated in third-party clinical trials. We are grateful to our study participants and to our investigators, who share our belief in the promise of single-course gene editing medicines for the treatment of cardiovascular disease. We look forward to initiating the Heart-2 clinical trial in the second quarter of this year.”