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Emerging Gene Therapy May Reduce the Painful Impact of Diabetic Peripheral Neuropathy

In a small sample size, the investigational DNA-based therapy showed statistically significant efficacy.

A PPM Brief

Helixmith (Seoul, South Korea) announced1 results showing that their VM202 (donaperminogene seltoplasmid) injection has met primary and secondary endpoints at 12 months in a Phase 3 extension study (DPN 3-1b) for painful diabetic peripheral neuropathy (DPN). VM202 is a novel, proprietary, non-viral, potentially regenerative plasmid DNA gene therapy; a genomic cDNA hybrid human hepatocyte growth factor (HGF) gene.

The January 2019 extension study (from an original 500-subject DPN 3-1 study) enrolled 101 subjects (n = 65 in the VM202 group; n = 36 in the placebo group); of these, 99 completed the full 3-month extension. The study included 12 of 25 clinical trial sites that actively participated in the original DPN 3-1 study. VM202 was also compared with gabapentin and pregabalin, two drugs also indicated for the treatment of DPN. Key results are detailed below.

Results of the study were presented at the 2019 Fall International Convention of The Pharmaceutical Society of Korea. (Image: iStockPhoto)

Safety and Efficacy

The extension study showed that VM202 appeared safe and well-tolerated. The occurrence of adverse events was no different between the VM202 and placebo groups; treatment-emergent adverse event occurrence rate was lower in the VM202 group (21.5%) than in the placebo group (25.0%). No serious adverse events were observed.

In the intent-to-treat population (n = 101), VM202 showed clinically meaningful and statistically significant pain reductions compared to placebo at Months 6, 9, and 12. The pain reduction differences between the two arms at Months 6, 9, and 12 were –1.1, –0.9, and –0.9, respectively. The data showed a trend toward efficacy at 3 months after the initial injection, but the difference was not statistically significant.

Greater Efficacy in Subjects Not Taking Gabapentin and Pregabalin

The difference in pain reduction between the VM202 and placebo groups was greater in the population not on gabapentinoid medication (n = 53 total, of which 34 subjects received VM202 and 19 subjects received placebo). At 6, 9, and 12 months, the pain reduction differences vs placebo were –1.34, –1.24, and –1.48.

Regeneration Potential

The last follow-up visit occurred at 12 months from the first injection of VM202 and 8.7 months, or 261 days, from the last injection of VM202, which occurred at Day 104. Bioanalytical data showed that 99.9999% of VM202 DNA disappeared from the systemic blood circulation at 3 days after injecting VM202 into the calf muscle, and the human HGF gene was expressed for merely 2 weeks after injection, suggesting that the therapy may offer nerve regeneration properties.

DPN develops over time and is one of the four main types of diabetes-related nerve damage (also including proximal neuropathy, autonomic neuropathy, and focal neuropathy). Researchers contribute the formation of DPN on poor blood glucose control, damaging blood vessels (age/lifestyle; nerve injury; and autoimmune, genetic, and metabolic factors may also contribute). According to the National Institute of Diabetes and Digestive and Kidney Diseases, 60% to 70% of people with either type 1 or type 2 diabetes will develop a type of diabetic nerve pain.

Last updated on: November 15, 2019
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