Completing its pharma comeback story, Verve Therapeutics announced successful results from the Heart-2 Phase 1b Clinical Trial of its in-vivo base editing drug, VERVE-102, that targets the PCSK9 gene for reducing LDL-C.
- PCSK9 is a molecule that breaks down LDL receptors, so drugs that inhibit it force the body’s LDL receptors to work harder, which reduces LDL-C more efficiently.
- Currently there are two FDA approved PCSK9 inhibitors, Amgen’s Repatha (evolocumab) and Regeneron’s Praluent (alirocumab), both of which are injected every three months.
- VERVE-102 is different since it edits and inactivates the gene responsible for PCSK9 production, meaning a single injection could permanently lower a patient’s LDL-C levels.
VERVE-102’s topline results come from a small group of 14 patients across three different dose cohorts (weight-based cohorts of 0.3, 0.45, and 0.6mg/kg) with at least 28 days of follow-up for each participant.
- After 28 days, researchers found that a single infusion of VERVE-102 led to an average LDL-C reduction of 53% with a maximum reduction of 69% in the 0.6mg/kg dose cohort.
- The 0.3mg/kg cohort saw a 21% LDL-C reduction and a 46% PCSK9 reduction, while the 0.45mg/kg cohort saw a 41% LDL-C and 53% PCSK9 reduction.
Not only was VERVE-102’s gene editing effective, it was also safe, with no treatment-related serious adverse events and no clinically significant changes in ALT or platelets observed at any dose level.
- This stems from VERVE-102’s proprietary GalNAc-LNP delivery technology, which allows the drug to access liver cells and demonstrates a potentially best-in-class safety profile.
These successful results mark a comeback for Verve considering the adverse events that led to the discontinuation of its earlier LDL-C drug, VERVE-101.
- Now with the topline success of VERVE-102, Verve will move on to Phase 2 of Heart-2 with a fourth dose cohort of 0.7mg/kg while it awaits Eli Lilly’s PCSK9 opt-in decision.
- Under a PCSK9 collaboration agreement with Verve, Lilly can opt-in to share worldwide development expenses (33% from Lilly) and profits in the U.S. on a 50/50 basis.
The Takeaway
Although we’re still very early in the gene editing space, and even earlier in single-shot CVD treatments, a single-dose injectable for LDL-C could have a lot of appeal if the price is right, gene editing catches on, and if future trials yield similarly supportive results
