VM202, a plasmid DNA that expresses 2 isoforms of hepatocyte development issue, is each protected and efficient in offering long-lasting ache reduction in painful diabetic peripheral neuropathy (DPN), based on outcomes of a section 3-1b examine revealed in Medical and Translational Science.
Following optimistic efficacy and security information outcomes from section 1 and a pair of research, researchers performed a big scale, double-blind, placebo-controlled section 2 examine of VM202 for painful DPN. The examine was performed in 2 elements: the primary examine happened over 9 months (DPN 3-1; ClinicalTrials.gov identifier NCT02427464; N=500 contributors), adopted by a noninterventional 3-month security and efficacy extension that included a subset of later-enrolling foremost examine contributors (DPN 3-1b; ClinicalTrials.gov identifier NCT04055090; n=101).
Researchers hypothesized that VM202 administration would scale back the typical day by day diabetic peripheral neuropathy ache scores greater than placebo. The first efficacy endpoint was the imply 24-hour numerical score scale ache rating, recorded in a day by day ache and sleep diary at 3 months.
In each research, most contributors have been White (74.4% and 80.2%) with an total imply age of 61.5 years. Many contributors had comorbid circumstances, together with hypertension, dyslipidemia, and weight problems.
Between-group demographic and baseline traits have been comparable. On the time of randomization, roughly half of the contributors weren’t receiving both pregabalin or gabapentin to handle DPN.
Researchers assessed security primarily based on incidence of treatment-emergent adversarial occasions, severe adversarial occasions, and adversarial occasions of particular curiosity (injection web site reactions, ophthalmologic or acute cardiac occasions, foot ulcers, and signs of central nervous system despair).
In DPN 3-1, 72.6% of these handled with VM202 and 68.9% of these handled with placebo reported at the very least 1 treatment-emergent adversarial occasion. The commonest adversarial occasions have been infections and infestations, which have been comparable between teams.
Antagonistic occasions of particular curiosity occurred in 17.2% and 16.8% of VM202 and placebo sufferers, respectively. The commonest adversarial occasions have been diabetic retinopathy, peripheral edema, and pores and skin ulcers. The incidence of those occasions that have been deemed associated to the examine drug was low, with no distinction between teams.
Critical adversarial occasions have been reported in 9.6% of the VM202 group and 9.9% of the placebo group. Within the VM202 group, adenocarcinoma and vitreous hemorrhage have been “deemed presumably associated to the examine drug.” Three myocardial infarctions have been deemed not associated to the examine drug because of sufferers’ medical historical past.
In DPN 3-1b, 15.4% and 22.2% of VM202- and placebo-treated sufferers, respectively, skilled treatment-emergent adversarial occasions. Antagonistic occasions of particular curiosity have been skilled by 3.1% and a pair of.8% of VM202- and placebo-treated sufferers, and included peripheral edema, chest ache, and angina pectoris. One participant within the VM202 group and a pair of within the placebo group reported severe adversarial occasions, however all 3 of those contributors had related medical histories.
DPN 3-1 failed to satisfy the first endpoints, with between-group variations that weren’t statistically vital for any endpoint measure. When the contributors who weren’t receiving concurrent gabapentinoids have been analyzed individually (n=251), endpoints remained statistically nonsignificant in contrast with placebo.
In DPN 3-1b, efficacy information differed “strikingly,” regardless of comparable participant demographic and baseline traits. Though there was no vital ache severity distinction at baseline, there have been vital reductions within the major efficacy endpoints at 12 months within the VM202 group in contrast with placebo. Important ache reductions have been additionally famous at 6 and 9 months, and higher ache reductions have been recognized in sufferers who weren’t taking gabapentin or pregabalin through the 12-month examine, which was in step with Part 2 examine outcomes.
The researchers acknowledged, “To our information, that is the primary Part 3 gene remedy examine for ache that has ever been achieved. VM202 didn’t meet efficacy endpoints within the full…inhabitants, however VM202 demonstrated long-term, clinically vital reductions in ache in [DPN 3-1b], significantly in [participants] not on gabapentinoids”
They concluded, “Given the wonderful security profile of VM202, the potential for illness modifying results, and the excessive unmet medical wants of the DPN affected person inhabitants not on gabapentinoids, additional examine is warranted.”
Disclosure: This medical trial was supported by Helixmith Inc. Please see the unique reference for a full record of authors’ disclosures.
Kessler JA, Shaibani A, Sang CN, et al; for the VM202 Examine Group. Gene therapy for diabetic peripheral neuropathy: a randomized, placebo-controlled phase 3 study of VM202, a plasmid DNA encoding human hepatocyte growth factor. Printed on-line January 19, 2021. Clin Transl Sci. doi:10.1111/cts.12977