HONG KONG – South Korea's Helixmith Co. Ltd. has announced the results of a phase III trial extension testing VM-202 (donaperminogene seltoplasmid), a regenerative plasmid DNA gene therapy candidate, in diabetic peripheral neuropathy (DPN). But, while the Seoul-based company, formerly known as Viromed, said VM-202 met the primary safety and secondary efficacy endpoints for a DPN therapy at 12 months, investors are doubting that the results are trustworthy.

The latest announcement, disclosing phase III-1b results, includes supplemental data to the previously reported phase III-Ia results. On Sept. 24, Helixmith said the III-Ia trial had failed to reach accurate conclusions for VM-202 due to data contamination. That contamination involved the company detecting VM-202 in patients assigned to the placebo group, an announcement investors clearly perceived as a failure of the clinical trials. The DPN phase III-Ib study aimed to assess the drug candidate's safety and efficacy at 12 months from the first injection among patients who participated in the DPN III-Ia study. The extension study, which started in January, enrolled 101 subjects, including 65 from the VM-202 subgroup and 36 from the placebo subgroup of the original 500 subjects in the DPN III-Ia study. The company said 99 of the 500 subjects completed the full three-month extension period.

The phase III-Ib study results include four key points: safety, efficacy (pain reduction), greater efficacy in subjects not taking DPN medications gabapentin and pregabalin, and regeneration potential.

VM-202 appeared to be safe. The treatment-emergent adverse event (AE) occurrence rate was lower in the VM-202 group (21.5%) than in the placebo group (25%). The results showed no serious adverse events (SAEs) related to the medication.

Also, the drug candidate showed clinically meaningful and statistically significant pain reduction vs. the placebo at months six, nine and 12 in the 101 intent-to-treat (ITT) population (p=0.010, p=0.044 and p=0.046, respectively). The pain reduction differences between the two arms at months six, nine and 12 were -1.1, -0.9 and -0.9, respectively.

The differences in pain reduction between the VM-202 and placebo groups were also bigger in the population not on gabapentinoid medication. The pain reduction variations vs. placebo were -1.34, -1.24 and -1.48 at six, nine and 12 months (p=0.031, p=0.050 and p=0.016, respectively).

Lastly, data showed that 99.9999% of VM-202 DNA is gone from systemic blood circulation three days after injecting VM-202 into the calf muscle, and the human hepatocyte growth factor (HGF) gene was expressed for two weeks after injection.

The fact that the VM-202 group sustained pain reduction for more than eight months in the absence of DNA and protein expressed by the gene suggests that the drug may have nerve regeneration properties, according to the company.

Another trial ahead

Helixmith will conduct another clinical trial, III-II, for VM-202 in DPN, which is expected to finish by 2020, followed by one year of tracking observation. The number of subjects will be around 150, as that will speed up the potential FDA biologics license application (BLA) process, a spokesman at Helixmith told BioWorld.

VM-202 has been designated as a regenerative medicine advanced therapy, which might be beneficial in terms of expediting the FDA approval process, the spokesman said. The candidate's main indication is DPN; however, the company plans to expand the indications to include amyotrophic lateral sclerosis and Charcot-Marie-tooth disease, peripheral artery disease and coronary artery disease.

Helixmith's share price (KOSDAQ:084990) closed at KRW89,800 (US$75.67) on Oct. 16. The stock reached as high as KRW204,100 on Sept. 17, and after its VM-202 trial III-Ia result announcement, the price fell down to KRW64,400 on Sept. 30.

Market expectations for VM-202 are rising again; however, some investors said the phase III-Ib results are not a good basis for investment.

And some analysts said that investors in Korea's biopharmaceutical companies should be more prudent.

"The stock price rise seems to be based on investment psychology rather than an actual performance. It seems safer to invest in large pharmaceutical or biosimilar companies," Byunghwa Han, analyst at Eugene Investment & Securities Co. Ltd., told BioWorld.

Detractors pointed to the fact that the III-Ib data are not valid for a BLA filing. The III-Ib study was conducted under a separate protocol that was submitted to the FDA, and the results were not approved by the agency. Also, the phase III-Ib study only had 101 subjects, far fewer than the phase III-Ia trial's 500 subjects.

Assuming success with the upcoming III-II trial approved by the FDA, Helixmith aims to submit the BLA by early 2022. The phase III-II will be conducted with three groups of the patients, and the most effective data among the groups will be used in the BLA, the company said.

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