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Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia

Gene Therapy volume 23, pages 306–312 (2016)Cite this article

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A Corrigendum to this article was published on 07 April 2016

Abstract

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5±17.8 versus 36.6±24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

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Acknowledgements

We acknowledge the dedicated collaboration with Emile R. Mohler, MD, Director of Vascular Medicine, University of Pennsylvania Health System; Tracie C. Collins, MD, MPH, Chair & Professor, Kansas Public Health Department; and J. Michael White, PhD at JM White Associates, who are DSMB members. Funded by ViroMed Co., Ltd, Seoul, Korea and supported by the Industrial Strategic Technology Development Program (grant no. 10031644, 'Clinical development of cardiovascular therapeutics (VM202) using novel hepatocyte growth factor gene in the US') funded by the Ministry of Trade, Industry & Energy (MI, Korea).

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Authors and Affiliations

  1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    M R Kibbe & D W Losordo

  2. University of Minnesota Medical School, Minneapolis, MN, USA

    A T Hirsch

  3. Cardiology P.C. Research, Birmingham, AL, USA

    F O Mendelsohn

  4. The Methodist Hospital, Houston, TX, USA

    M G Davies

  5. Boston University School of Medicine, Boston, MA, USA

    H Pham & V Driver

  6. University of Oklahoma HSC, Oklahoma City, OK, USA

    J Saucedo

  7. University of North Carolina School of Medicine, Chapel Hill, NC, USA

    W Marston

  8. Ewha Womans University Medical Center, Seoul, Korea

    W-B Pyun

  9. Seoul National University Hospital, Seoul, Korea

    S-K Min

  10. Saint Louis University Hospital, Louis, MO, USA

    B G Peterson

  11. Jobst Vascular, Toledo, OH, USA

    A Comerota

  12. Yonsei University Severance Cardiovascular Hospital, Seoul, Korea

    D Choi

  13. Vascular & Interventional Specialists of Orange County, Inc., Orange, CA, USA

    J Ballard

  14. Stem Cell Center, Texas Heart Institute, Houston, TX, USA

    R A Bartow & E C Perin

  15. Columbia University Medical Center, New York, NY, USA

    W Sherman

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  1. M R Kibbe
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  2. A T Hirsch
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  9. S-K Min
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  15. D W Losordo
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  16. W Sherman
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  17. V Driver
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  18. E C Perin
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Corresponding author

Correspondence to E C Perin.

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Competing interests

Warren Sherman receives consulting fees from ViroMed. The remaining authors declare no conflicts of interest. We retain sole responsibility for the data, statistical analysis and manuscript content.

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Supplementary Information accompanies this paper on Gene Therapy website .

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Kibbe, M., Hirsch, A., Mendelsohn, F. et al. Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia. Gene Ther 23, 306–312 (2016). https://doi.org/10.1038/gt.2015.110

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  • DOI: https://doi.org/10.1038/gt.2015.110

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