Placebo-drug mix-up adds subplot to Helixmith phase 3 failure

A phase 3 trial of Helixmith’s DNA plasmid gene therapy in painful diabetic peripheral neuropathy (DPN) has missed its primary endpoint. Helixmith, formerly known as ViroMed, pointed to evidence that people in the placebo cohort had received the experimental therapy as a potential explanation for the failure.

The therapy, VM202, is a DNA plasmid that encodes for both isoforms of hepatocyte growth factor (HGF). By administering the drug to DPN patients, Helixmith hoped to harness the neurotrophic and angiogenic properties of HGF to counter the nerve damage associated with the condition, thereby lessening the pain experienced by people with the disease.

To test that idea, Helixmith enrolled 500 people with DPN and randomized them to receive intramuscular injections of VM202, also known as Engensis, or placebo at four time points over the course of the nine-month study.

The headline finding is that VM202 was no better than placebo at reducing pain scores over the first 90 days of the trial. That is only part of the story, though. Helixmith claims the data may have been compromised by a major mix-up in the execution of the study.

An analysis of samples taken from people in the placebo arm found DNA used in VM202, suggesting investigators may have administered the experimental therapy to people in the control group. The analysis also showed some people in the VM202 cohort had far lower concentrations of VM202 DNA than others. 

In a release to disclose the results, Helixmith said “it is difficult to determine the precise reason for these results.” However, Helixmith was more forthcoming at a local press conference attended by The Korea Times. 

"As the drug was mixed up, placebo group patients showed increased effect in pain alleviation, while Engensis group subjects showed an adverse result," Helixmith CEO Kim Sun-young said

According to The Korea Herald, Kim thinks the management of the trial may have been compromised by a sharp increase in patient enrollment. The trial took place at 25 sites in the U.S. Helixmith has formed a team to investigate the findings.

In parallel, Helixmith will work to start two or three smaller trials to generate more data on VM202. Helixmith expects to initiate the trials within the next six months and deliver data early in 2022. 

The situation, regardless of whether it was caused by an ineffective drug or poor trial execution, is another blow for the Korean biotech industry. In 2019, HLB Company, Kolon Life Science and Sillajen have all suffered major setbacks, wiping sizable slices off multibillion-dollar market caps.