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Gene Therapy Promotes Wound Closure of Diabetic Foot Ulcers

VM202 was found to be particularly effective in treating neuroischemic ulcers.

The novel gene therapy VM202 (Engensis; Helixmith) has shown efficacy in treating diabetic foot ulcers, according to data from a phase 3 study (NCT02563522) presented at the 2021 annual meeting of the Diabetic Foot Conference, October 21-23.1

Investigators observed a positive trend toward wound closure in treated patients between months 3 and 7 post treatment, particularly patients with neuroischemic ulcers. Treated patients with these ulcers had significantly more complete ulcer closures than control (P = .0391, .0391, and .0361 at months 3, 4, and 5 respectively).

"Diabetic foot ulcers are one of the most serious complications associated with diabetes, contributing to high levels of morbidity, mortality, and health-care costs in this population, and there have been limited treatment options to date," said principal investigator David G. Armstrong, DPM, MD, PhD, professor, surgery, and co-director, USC Limb Preservation Program, Keck School of Medicine, University of Southern California, in a statement.1 "Given the safety profile and potential healing effects we identified in this study, continuing a larger DFU study is warranted with iterations of the current protocol and expansion of the number of sites."

The randomized, double-blind, placebo-controlled, multicenter study assessed the safety and efficacy of VM202 administered as intramuscular injections to the calf in patients with chronic nonhealing foot ulcers with concomitant peripheral artery disease. The study has a target enrollment of 300 patients to be randomized in a 2:1 ratio to VM202 or placebo groups. 

READ MORE: Diabetes Cell Therapy Improves Insulin Production in First Patient Dosed

The study is primarily assessing efficacy as measured by target wound closure by 4 months. Secondary outcome measures include time to complete wound closure, time to amputation, change in ankle brachial index (ABI) and toe brachial index, and change in Core Welfare Indicators Questionnaire domain scores.

Investigators observed wound closure in the interim intent-to-treat (ITT) population of 44 participants. Twenty-three participants had neuroischemic ulcers, in which VM202 was seen to be most effective. Investigators also observed a potentially clinically meaningful 0.15 increase in ABI in the ITT population at day 210 (P = .0776).

VM202 is a non-viral plasmid DNA gene therapy designed to express recombinant human hepatocyte growth factor (HGF) protein in nerve and Schwann cells to promote regeneration and microvascular blood vessel formation. The therapy also addresses the issue of HGF’s short half-life that prevents effective treatment with the hormone. 

The FDA previously granted the therapy Regenerative Medicine Advanced Therapy for the treatment of painful diabetic peripheral neuropathy. VM202 previously showed efficacy in this indication in a phase 3 study (NCT02427464).2 While the first part of the study, which assessed 500 participants over 9 months, did not meet its primary endpoint of change from baseline in mean 24-h Numerical Rating Scale (NRS) pain score, the second part of the study, assessing 101 participants over 12 months, demonstrated significant and clinically meaningful pain reduction versus placebo.3 

An analysis of the second part of the study revealed significant reductions in the 24-hour average pain scores at 6 months and 9 months in the treated group. Greater pain reductions were also observed in subjects who were not on gabapentin or pregabalin during the 12-month study. The therapy was well-tolerated in both parts of the study.

“The thorough analysis of the Phase 3 study affirms the promise for Engensis to become a much-needed treatment option for painful DPN – one that again suggests a strong safety profile and durable efficacy, with potential effects on disease progression. The stronger efficacy shown among patients not on gabapentinoids is important because patients only have opioids as a treatment option today,” William Schmidt, PhD, senior vice president, clinical development, Helixmith, said in an earlier statement.2 “The experiences gained in this study has guided the design of an additional Phase 3 study [NCT04055090] that recently began enrollment.”

REFERENCES
1. Helixmith announces phase 3 study results of novel gene therapy treatment for diabetic foot ulcers at 2021 Annual Meeting of Diabetic Foot Ulcer Conference (DFCon). News release. Helixmith. October 22, 2021. https://www.prnewswire.com/news-releases/helixmith-announces-phase-3-study-results-of-novel-gene-therapy-treatment-for-diabetic-foot-ulcers-at-2021-annual-meeting-of-diabetic-foot-ulcer-conference-dfcon-301405923.html
2. Results from phase 3 gene therapy trial for painful diabetic peripheral neuropathy has been published online by Clinical and Translational Science. News release. Helixmith. March 13, 2021. https://www.helixmith.com/bbs/board.php?bo_table=s5_1_eng&wr_id=35
3. Kessler JA, Shaibani A, Sang CN, et al. Gene therapy for diabetic peripheral neuropathy: A randomized, placebo-controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor. Clin Transl Sci. May 2021; 14(3):1176-1184. doi: 10.1111/cts.12977