Human hepatocyte growth factor injections (HGF; VM202, ViroMed), administered twice over 2 weeks, show efficacy in significantly reducing diabetic peripheral neuropathic pain for up to 3 months without any significant adverse effects, new research suggests.
Co-author John Kessler, MD, a professor of neurology at Northwestern University’s Feinberg School of Medicine said “We found that patients who were not taking pregabalin or gabapentin responded particularly well to HGF, and that’s particularly important because some patients are unable to take these drugs or don’t respond to them, so we would have something to offer those patients with this”.
HGF is known to have trophic effects on peripheral sensory, sympathetic, and motor neurons, nourishing neuronal survival and axonal growth, Dr Kessler and the authors explain.
“HGF’s potent neurotrophic and angiogenic properties make it the ideal candidate for the treatment of painful diabetic neuropathy,” they write.
For the double-blind study, presented here at the American Neurological Association (ANA) 2015 Annual Meeting, 104 patients with painful diabetic neuropathy were randomly assigned to receive intramuscular injections in the calves, with 8 mg of the plasmid VM202 per leg, 16 mg per leg, or placebo. The injections were administered 2 weeks apart.
Among 96 patients who completed the study, those in the low-dose group (n = 40) reported the greatest improvement in all measures of efficacy and a significant reduction in mean pain score at 3 months (P = .04), as determined by scores on the Daily Pain and Sleep Interference Diary, which quantified participants’ average 24-hour pain and sleep interference.
The authors reported that pain reductions persisted at 6 and 9 months but were not statistically significant.
Patients in the low-dose group who were not taking pregabalin or gabapentin (n = 49) reported the largest reductions in pain in terms of scores on the Daily Pain and Sleep Interference Diary, showing a significant 3.7-point reduction in pain at 3 months (P = .02). Their pain reduction was maintained at 6 months (P = .03) and 9 months (P = .08).
The authors speculated that the findings suggest an interaction between pregabalin or gabapentin and HGF.
“As there were no observable differences between these patient populations for any demographic, HbA1c [hemoglobin A1c] levels, duration of disease, or pain at study entry, this finding may suggest that the mechanism of action of these drugs somehow attenuates HGF activity,” they write.
In terms of other pain measures, patients in the low-dose group overall also reported the greatest degree of improvement on the Patient’s Global Impression (PGI) of Change questionnaire at 90-day and 6- and 9-month visits.
At 90 days, 48.4% (15 of 31) of patients in the low-dose group and 30.6% (11 of 36) of patients in the high-dose group reported being much or very much improved on the PGI scale, with a reduction in pain greater than 50%, compared with only 17.6% (3 of 17) of patients in the placebo group.
Reductions in pain severity, determined by using the Brief Pain Inventory for Diabetic Peripheral Neuropathy, were significant in the low-dose group at 3 and 6 months compared with placebo (–41.95% at 3 months [P = .06] and –37.71% at 6 months [P = .05]), while improvements in the pain severity score in the high-does group did not reach statistical significance.
Dr Kessler underscored that HGF/VM202 therapy is, importantly, a nonviral gene therapy, as opposed to other gene therapies that have been associated with complications linked to viruses expressed in the DNA.
While the study did not compare the therapy with pain improvement related to other drugs, the response appears greater than that typically expected with other medications, he said.
“If you look at the literature on pain response, we had a much greater reduction in pain than other medications, so it looks like it’s at least as effective, if not more, than existing therapies,” Dr Kessler said.
Patients also showed improvement in functions such as ability to sense light touch and mechanical touch, he added.
“So we may not just be improving pain but also function with the HGF therapy.”
During the study 13 serious adverse events occurred among 10 patients, but none were considered to be related to the study drug or placebo.
Twenty-six patients experienced grade 1 minor injection site reactions, with more than half in the high-dose group.
“One of the striking features of the HGF treatment is that there were virtually no side effects, which probably reflects the fact that the treatment was local rather than systemic,” the authors write.
Dr Kessler added that the ability to have pain reduction without the need for daily medication could be a significant benefit to diabetic patients with neuropathic pain.
“We’re looking at treating patients in two cycles four times a year as opposed to taking a medicine every day — that would be very helpful,” he said.
The researchers are moving ahead with a phase 3 study on VM202 that is scheduled to begin in January 2016, with approximately 477 patients to be evaluated in a 2:1 ratio of drug vs placebo.
The study was also published in the Annals of Clinical and Translational Neurology.
The study’s costs were paid for by ViroMed. Dr Kessler has disclosed no relevant financial relationships.
Source: American Neurological Association (ANA) 2015 Annual Meeting. Abstract M703. Presented September 28, 2015.