AMG0001 Advances Healing in CLTI with David G. Armstrong, DPM, PhD, and Michael S. Conte, MD

Gene therapy using AMG0001, a plasmid encoding hepatocyte growth factor (HGF), significantly shortened wound healing time and improved ulcer healing rates in patients with chronic limb-threatening ischemia (CLTI), according to featured science at the American Heart Association (AHA) Scientific Sessions 2024.

In the randomized, double-blind, placebo-controlled Phase 2 LEGEND 1 trial, 75 patients with neuro-ischemic ulcers and moderate CLTI were randomized to receive 4 monthly AMG0001 4 mg or 8 mg or placebo. Calf intramuscular injections targeted specific angiosomes based on wound location and imaging.

“We look forward to further work that will confirm this or refute it, but this is a real glimmer of hope in an area that needs it,” investigator David G. Armstrong, DPM, PhD, University of Southern California Keck School of Medicine, told HCPLive. “A lot of times, there haven’t been good therapies for these patients and they’ve been largely ignored. From that standpoint, they’re not going to be ignored anymore.”

Upon analysis, the median time to healing for AMG0001-treated ulcers was 84 days compared to 280 days in the placebo group (P = 0.0071). By 12 months, approximately 78% of ulcers in the treatment group achieved complete healing, compared to 46% in the placebo group (P = 0.0096).

The therapy also improved hemodynamics, with significant increases in the ankle-brachial index (0.13; P = 0.03) at six months and dorsal foot TcPO2 (18.5 mmHg; P = 0.02) at 12 months in the 4 mg group.

Although ulcer recurrence rates were lower in the AMG0001 group (32% vs. 50%), investigators indicated the difference was not statistically significant. Safety outcomes showed adverse event rates were evenly distributed among treatment groups, suggesting a tolerable safety profile.

The study highlights AMG0001 as a promising, well-tolerated therapeutic option for a patient population with limited alternatives, underscoring its potential to address an urgent unmet clinical need in CLTI care.

“We focused on the healing of the wounds, rather than death and major amputation, as a way to see if the gene therapy was beneficial biologically and clinically,” investigator Michael S. Conte, MD, UC San Francisco, told HCPLive. “I think all of that in this trial showed promising results, so we’re excited to move forward into a larger Phase 3 trial.”

Disclosures: Armstrong reports relevant disclosures with AnGes, Podimetrics, Endo Pharmaceuticals, Janssen, and Nevro. Conte reports relevant disclosures with Anges, Medistim, and Pfizer.

Reference

_{Armstrong DG, Conte MS, Mills JL, Menard M, et al. Anatomically Directed Lower Extremity Gene Therapy for Ulcer Healing: A Double-Blind, Randomized, Placebo-Controlled Study. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.}