CMT Blog

The HNF sent out a short notice yesterday about a new Phase 1 and 2a clinical trial for VM202 (Engensis) from Seoul-based Helixmith, previously known as ViroMed. This is a drug that Helixmith hopes will reduce nerve pain for people with CMT1a as an alternative to Lyrica (Pregabalin) and Neurontin (Gabapentin). (If it panned out, that would be a good thing — Pregabalin and Gabapentin have some unpleasant side-effects and potential for addiction.)

VM202’s promise appears to have faded a lot since its debut in clinical trials. It seems the new hope for VM202 as a CMT1a treatment is perhaps Helixmith’s latest attempt to find a market for an experimental product that has not panned out as hoped for other diseases.

It seems the new hope for VM202 as a CMT1a treatment is perhaps Helixmith’s latest attempt to find a market for an experimental product that has not panned out as hoped for other diseases.

What is VM202?

The drug itself is a DNA plasmid — a small DNA molecule within a cell that’s not part of any chromosomal DNA but can replicate itself by itself. This could be described as “gene therapy.” The plasmid in VM202 encodes DNA for the human hepatocyte growth factor (HGF), which can help nerves and blood vessels regenerate by signalling to nearby cells at a short range (paracrine signalling).

Sorry, the placebo was laced with drugs…or maybe not?

PipelineReview.com summarizes the drug’s testing history: VM202 was developed to treat painful diabetic peripheral neuropathy (DPN), amyotrophic lateral sclerosis (ALS), coronary artery disease, and foot ulcers associated with diabetes.

CMT does not seem to have been in the original target market for VM202. Instead, DPN — likely a much bigger market — was the subject of the first trials.

The first Phase 3 trial in 500 DPN patients failed to show a reduced experience of pain after nine months that differed from a placebo group. 101 people in this test group continued to be given the drug for another three months, which established the drug is at least safe enough to take for a year without major adverse effects showing up. A significant analgesic (pain reduction) effect was reported as well — with the smaller, extended study group.

Helixmith hopes the reported pain reduction — as one point on the scale they used — indicates that VM202 regenerates damaged nerves. (Presumably this would be the only way a plasmid for HGF could reduce nerve pain.)

After the disappointing first test results, Helixmith alleged there had been a mixup where the drug was given to a placebo group. The company did not bring the study to a conclusion then as expected due to the data contamination they believed had occurred. Then, following an investigation, Helixmith said nothing was wrong, and their original data from the trial was valid!

During this fiasco, the company’s stock received a “Sell” rating from Goldman-Sachs, and it took a plunge on the Korean market from which it has never recovered; it is now trading at around $50, down from $200 a year ago.

🤯 Amber Tong has a trenchant commentary about this slide over at Endpoint News.

Will VM202 help people with CMT1a? Maybe, maybe not. We can surely hope, but Helixmith’s performance in the trials so far is far from reassuring.

Researching this topic motivated me to ask out loud a question I’ve had for a while: what condition is the Food and Drug Administration’s condition in these days? Some recent articles on that subject I’d like to dig into later:

• Science is not amused: FDA enforcement actions plummet under Trump
  “If the FDA isn’t doing enforcement, nobody’s doing enforcement.”
• PwC (PricewaterhouseCoopers) is one of the Big Four accounting firms invested in risk assessment and used to mincing words a bit. They say the glass is half full: Continue to take as prescribed: Amid a steep slowdown in regulation, the FDA hit record highs for drug approvals while maintaining enforcement.

🧪 If you have CMT1a and would like to participate in the latest trial, you can head over to GRIN and bare your personal medical data. 👩‍💻