Inclisiran sodium

Verve Therapeutics is trying to swerve the gene editing industry downturn with new results on a potential one-time treatment to lower cholesterol. The experimental gene editing therapy cut bad cholesterol by levels comparable to approved heart disease treatments in an early-stage study. VERVE-102 is designed to edit the gene for PCSK9, a protein that’s key in regulating cholesterol, and is Verve’s second clinical program targeting that gene. In 14 patients studied so far, Verve has not seen the substantial elevations in liver damage markers that sidelined its first program. The readout has been closely watched in a gene editing industry that has had little to celebrate recently. After Verve wraps its Phase 1b later this year, Eli Lilly is expected to decide if it wants to opt in to the PCSK9 program. Verve is studying VERVE-102 in a hereditary high cholesterol condition called heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (where heart disease occurs in men and women younger than 45 and 55, respectively). In four patients who received the highest dose (0.6 mg/kg), Verve reported that the gene editing treatment lowered levels of bad cholesterol by an average of 53%. In those patients, the treatment also lowered PCSK9 levels by 60%. At the lower two doses (0.3 mg/kg and 0.45 mg/kg), Verve’s treatment cut bad cholesterol levels by 41% and 21% on average as of its March 13 data cutoff. Most of the Phase 1b patients also took statins. By comparison, Novartis’ twice-yearly PCSK9 shot Leqvio lowered cholesterol by about 40% in a key clinical trial with HeFH patients. Verve’s shares $VERV jumped 22% in pre-market trading, though they are down more than 50% over the past 12 months. Verve also reported no significant safety concerns with VERVE-102. The company’s first PCSK9-targeted gene editing treatment was paused after a patient experienced increased liver enzymes and low blood platelet counts. That earlier program was the first instance that base editing — a newer version of gene editing — was used directly in humans. Verve CEO Sek Kathiresan told Endpoints News that the first program’s safety challenges were due to the lipid nanoparticle, which is the fatty acid envelope the therapy uses to deliver the gene editing technology. The new program uses a different lipid nanoparticle, which features targeting ligand called GalNAc to help liver cells bind the gene editing therapy. The current program uses the same gene editing cargo as the first. “It does really seem like we’ve been able to overcome that safety issue with this new product,” Kathiresan said. On Monday, Verve also presented results showing that its first gene editing therapy, VERVE-101, led to a lasting reduction in cholesterol through 18 months with six patients who received a low dose and through two years with one patient who received a high dose. While Verve has one more dose level of 0.7 mg/kg to examine in its early-stage study, it is planning to move away from weight-based dosing. As part of its presentation on Monday, Verve showed that the total RNA dose correlated closely with the decrease in bad cholesterol. So far, patients in Verve’s study received up to 60 mg of RNA. Verve is following in the footsteps of Intellia Therapeutics, which is studying single 55 mg and 50 mg doses of its ATTR amyloidosis and hereditary angioedema gene editing treatments in pivotal studies, respectively. “The field overall is moving to this fixed dose paradigm,” Kathiresan said. Verve expects to read out full Phase 1b data, including that last cohort, at a major medical meeting later this year, Kathiresan said. The biotech has already dosed two patients in that highest cohort as of April 7. In March, Verve received clearance from the FDA to begin testing VERVE-102 in the US. It plans to include US sites in its Phase 2 study, which it expects to begin dosing in the second half of the year. The current study is running in the UK, Canada, Israel, Australia and New Zealand. Verve had $524.3 million in cash at the end of 2024, which it said it expects to fund operations into mid-2027. It said Monday that would keep it operating through completion of the Phase 2 clinical trial. Editor’s note: This story was updated to include Verve’s stock move.