The first patient has been dosed in a Phase III trial assessing ViroMed’s VM202, the first pivotal study of a gene therapy indicated for patients with nonhealing diabetic foot ulcers (NHU) and concomitant peripheral artery disease (PAD).

The Phase III trial (NCT02563522) is a double-blind, placebo-controlled, multicenter study designed to evaluate VM202 for safety and efficacy in 300 adults with a diabetic foot ulcer and concomitant PAD. Two hundred patients will be randomized to VM202 and the other 100 to placebo, ViroMed’s U.S. division VM BioPharma said yesterday.

Patients will receive ongoing wound care for the duration of the trial, the company added.

The primary clinical endpoint will be the proportion of subjects with confirmed target wound closure by the 4-month follow-up. Secondary endpoints will include changes in ankle-brachial index and toe-brachial index.

The trial is the second Phase III study of VM202; the first study assessed the drug in another indication, painful diabetic peripheral neuropathy.

VM202 is a plasmid DNA containing the human hepatocyte growth factor (HGF) gene that in vivo produces two isoforms of HGF proteins naturally found in the human body. HGF is a growth factor that induces angiogenesis and acts as a neurotrophic factor to the peripheral nervous system.

Upon injection into a patient's muscle, VM202 is taken up by cells that produce the HGF protein. VM202 is believed to provide clinical benefit to patients with diabetic NHU, since upon its release from skeletal muscle cells, HGF may induce new blood vessel formation locally by activating various signaling pathways.

“This is a unique and promising approach to addressing nonhealing wounds,” said David Armstrong, DPM, M.D., Ph.D., co-principal investigator of the Phase III study and distinguished outreach professor of surgery at the University of Arizona and director of the Southwestern Academic Limb Salvage Alliance (SALSA).

‘Revolutionary’ Potential

“A positive outcome could be revolutionary in a population with limited or no options for improving their chance of complete ulcer healing,” Dr. Armstrong added.

Current standard of care for NHU includes debridement of the wound, management of any infection, revascularization procedures when they are indicated, mechanical offloading of the ulcer, blood glucose control, and foot care education. However, these strategies produce healing in only about half of ulcers, while 25% of open wounds progress to gangrene or require amputation.

Worse, development of new drugs for diabetic foot ulcer has been stymied by clinical trial setbacks. In August 2016, Adocia halted development of BioChaperone® (BC) PDGF for diabetic foot ulcer following its failure in a Phase III trial. Two months later in October 2016, Dipexium Pharmaceuticals acknowledged topline results showing that its diabetic foot ulcer candidate Locilex® (pexiganan cream 0.8%) failed two Phase III trials. Dipexium has since merged with PLx Pharma, in a deal completed April 19.

VM202, however, showed potential last year in a Phase II trial for treating foot ulcers in critical limb ischemia patients taking both high (16 mg total) and low (8 mg total) doses. For ulcer healing, 62% of ulcers treated with high-dose VM202 healed completely, compared to 11% of ulcers treated with placebo 12 months after treatment. Also, 71% of high-dose VM202 patients showed increased transcutaneous oxygen (TcPO2) levels, versus 33% of placebo patients.

“There have been numerous efforts to treat foot ulcers, mostly involving complex wound dressings. VM202 stands to alter the lower leg's ischemic environment, one of the critical causes of this condition, and these pivotal data will help us better understand the potential of this novel approach that could improve the quality of life for the millions of patients who suffer from this debilitating condition,” added ViroMed CSO Sunyoung Kim, D.Phil.

VM202 has also succeeded in a Phase II trial in patients with painful diabetic peripheral neuropathy and advanced in that indication to an ongoing Phase III study (NCT02427464). The candidate has also successfully completed a Phase I/II study for amyotrophic lateral sclerosis (ALS) in the U.S, while a Phase I trial is to be launched in South Korea evaluating VM202 in coronary artery disease.

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