Beperminogene perplasmid for the treatment of critical limb ischemia

Abstract

Therapeutic angiogenesis for the treatment of ischemic disease can be attained through the delivery of recombinant growth factor proteins, through gene transfer or cell transplantation. Gene transfer associated with adenovirus or naked plasmid DNAs has been extensively studied in clinical trials. An investigational product, beperminogene perplasmid, is the naked plasmid DNA encoding the cDNA of human HGF, which has potent angiogenic activity. In several clinical trials, beperminogene perplasmid showed favorable safety and efficacy profile in the treatment of critical limb ischemia. This article reviews the results of pre-clinical and clinical studies of beperminogene perplasmid in the treatment of critical limb ischemia caused by peripheral arterial disease and Buerger’s disease.

Keywords::

• angiogenesis
• atherosclerosis
• Buerger’s disease
• critical limb ischemia
• gene therapy
• HGF

Financial & competing interests disclosure

The Department of Clinical Gene Therapy was financially supported by Mitsubishi-Tanabe, Daiichi Sankyo, AnGes MG, Novartis, Shionogi, Boeringher and Rhoto. R Morishita is a founding stock holder of AnGes MG, who developed beperminogene perplasmid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Beperminogene perplasmid is naked plasmid DNA encoding and producing human HGF. Several clinical studies indicate favorable efficacy results in the critical limb ischemia subjects.

• In AG-CLI-0202, obvious increase of tissue perfusion in the ischemic limb was observed in the beperminogene perplasmid group.

• In AMG0001-JN-101, a significant improvement of clinical symptoms was shown in HGF group.

• A large-scale Phase III trial is being conducted to verify the prevention of major amputation and all-cause death.

Notes