VERVE-102 is an experimental gene editing therapy developed by Verve Therapeutics, a biotechnology company based in Cambridge, Massachusetts. The treatment targets a genetic form of high cholesterol known as heterozygous familial hypercholesterolemia (HeFH). HeFH affects roughly 1 in 250 people worldwide and causes dangerously high levels of low-density lipoprotein (LDL) cholesterol from birth, leading to premature heart attacks and strokes if untreated. VERVE-102 uses base editing, a technology that makes precise single-letter changes in DNA, to permanently turn off the PCSK9 gene in liver cells. This approach aims to lower LDL cholesterol with a single infusion, potentially replacing daily statin pills or periodic injections of PCSK9 inhibitors like evolocumab (Repatha) or alirocumab (Praluent). Verve Therapeutics went public in June 2021, raising $198 million in its initial public offering. The company's lead candidate, VERVE-101, was the first in vivo base editing therapy to enter human clinical trials in 2022. VERVE-102 is a next-generation version designed to improve delivery and efficacy. The FDA's decision on VERVE-102's approval would represent a major regulatory milestone for gene editing therapies that are administered directly to patients, as opposed to editing cells outside the body and then infusing them. No gene editing therapy for a common chronic disease has received FDA approval to date. The FDA has not yet set a decision date for VERVE-102, as the therapy is still in early clinical trials. The market resolves to Yes if the FDA issues an approval letter for VERVE-102 before January 1 of a specified year. Investors, patients with HeFH, and the broader gene editing industry are watching this closely because approval would validate in vivo gene editing as a viable treatment platform for millions of people with chronic diseases. It would also set a precedent for how the FDA regulates permanent genetic modifications that are not intended to be heritable.

Historical Context

The history of gene editing therapies began with the discovery of CRISPR-Cas9 in 2012 by Jennifer Doudna and Emmanuelle Charpentier, who won the Nobel Prize in Chemistry in 2020. The first clinical applications of CRISPR involved editing cells outside the body, such as in the 2019 trial for sickle cell disease conducted by Vertex Pharmaceuticals and CRISPR Therapeutics, which led to the approval of Casgevy in December 2023. In vivo gene editing, where the editing machinery is delivered directly to cells inside the body, has been slower to develop due to challenges with delivery and safety. Verve Therapeutics initiated the first in vivo base editing clinical trial in humans in 2022 with VERVE-101. In November 2023, Verve reported interim data from that trial showing that VERVE-101 reduced LDL cholesterol by 39% in one patient at the highest dose, but two patients experienced serious adverse events including one cardiac arrest. Verve paused enrollment in the VERVE-101 trial in 2023 to redesign the delivery system, leading to the development of VERVE-102. The FDA has approved only two gene editing therapies as of 2024: Casgevy for sickle cell disease and Lyfgenia for beta-thalassemia. Both are ex vivo therapies, meaning cells are edited outside the body. No in vivo gene editing therapy has been approved by the FDA. The regulatory pathway for VERVE-102 would likely require a Biologics License Application (BLA) submission, which typically takes 10-12 months for FDA review after submission. Verve has not announced a timeline for BLA submission for VERVE-102.