Recently, a paper reporting the long-term follow-up results of the Phase II clinical trial for the gene therapy drug “Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection” (code name NL003)—developed by our company—has been published in Vascular Investigation and Therapy (ISSN: 2589-9686). This journal is an academic publication sponsored by the International Union of Angiology (IUA). The first author and corresponding author of the paper is Professor Gu Yongquan from the Department of Vascular Surgery at Xuanwu Hospital of Capital Medical University.

        NL003 Project Phase II The Phase I clinical trial, led by Professor Gu Yongquan, was conducted at nine research centers across China from 2012 to 2014. The results showed that local intramuscular injection of NL003 could effectively alleviate resting pain and promote ulcer healing in patients with severe lower-limb ischemia, while demonstrating a favorable safety profile. These findings were published publicly in 2019 in Molecular Therapy (Gu Y et al., 2019;27:2158-65).

To further evaluate the long-term efficacy and safety of NL003 in patients with critical limb ischemia (CLI), Professor Gu Yongquan from the Department of Vascular Surgery at Xuanwu Hospital, Capital Medical University—principal investigator of the Phase II clinical trial—has initiated this long-term follow-up study. The study protocol has been reviewed and approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University, as well as by the Ethics Committee of Nanjing Gulou Hospital. Among the 197 subjects enrolled in the Phase II clinical trial, 109 subjects (55.3%) responded to telephone interviews, completed questionnaires, or provided medical documentation. The median follow-up duration for these subjects was 10.4 years (ranging from 9.2 to 11.6 years). The results showed that among subjects treated with NL003, the 5-year freedom-from-amputation survival rate was 67.1% (51 out of 76), significantly higher than the 37.5% (12 out of 32) observed in the placebo group; this difference was statistically significant (p=0.004). The median freedom-from-amputation survival time was 9.53 years in the NL003-treated group, compared to 4.51 years in the placebo group. In subgroup analyses involving patients with comorbid diabetes and Rutherford grades 4 and 5, the experimental drug group continued to demonstrate a favorable 5-year freedom-from-amputation survival rate. The Kaplan-Meier curves for freedom-from-amputation survival are shown in the figure below.

In terms of safety, during a follow-up period lasting 9 to 11 years, no increase in the incidence of malignancies was observed, nor were any long-term adverse events potentially associated with gene therapy noted.

The most significant finding of this study is that NL003 improved the 5-year limb-salvage survival rate and prolonged the limb-salvage survival period in patients, thereby having a positive impact on the long-term clinical outcomes of patients with severe lower-limb ischemia while demonstrating good long-term safety. The study results suggest that NL003 can provide long-term benefits for patients with severe lower-limb ischemia.

        NL003 treatment The long-term follow-up results of the Phase II clinical trial for the treatment of severe lower-limb ischemia are encouraging, further confirming the efficacy and safety of NL003 and providing robust data support for the New Drug Application (NDA) submission of NL003. The company is actively preparing the NDA documentation and strives to obtain regulatory approval at an early date, thereby enriching clinical treatment options and offering patients a new therapeutic choice.

Paper link:

https://journals.lww.com/vith/fulltext/2024/07010/nine_year_follow_up_of_patients_receiving.3.aspx

Full-text reference: Gu Y, Cui S, Yu T, Liao L, Guo J. Nine-year follow-up of patients receiving recombinant human hepatocyte growth factor nude plasmid DNA for critical limb ischemia: Updated safety and efficacy results. Vasc Invest Ther 2024;7:14-7.