Vico’s Trial Adjusts With Twice-Yearly Dosing, And The U.S. Is Next

In a press release from February 24th, 2026, Vico Therapeutics have announced that participants are now being dosed in a new fourth arm of their ongoing Phase 1/2a clinical trial of VO659, a drug being tested in people with Huntington’s disease (HD), spinocerebellar ataxia type 1 (SCA1), and spinocerebellar ataxia type 3 (SCA3). This new arm tests a less frequent dosing schedule, just twice a year, compared to earlier arms of the trial. In addition, Vico has received clearance from the U.S. FDA to begin testing VO659 in the United States, with hopes to begin as soon as later this year.

What is VO659 and how does it work?

VO659 is a type of drug called an antisense oligonucleotide, or ASO. ASOs are short stretches of genetic material designed to bind to specific message molecules inside cells, flagging them for destruction. Without that message molecule, the cell can’t make the protein it encodes. For diseases like HD, SCA1, and SCA3, that means lower levels of the toxic protein. 

Like other ASOs being tested in the clinic, VO659 is delivered by spinal injection so it can travel through the nervous system and reach the brain.

What makes VO659 particularly interesting is what it targets. Rather than going after a feature that is unique to the HTT gene, VO659 is designed to seek out the long strings of repeating CAG genetic letters that cause HD. Whilst VO659 hits both the regular and expanded forms of HTT, because the expanded form has more CAGs, the drug prefers this target so there is preferential lowering of the expanded HTT.

Importantly, HD isn’t the only disease caused by a CAG repetition. There are actually nine other diseases with this same type of genetic cause, including SCA1 and SCA3. In people with SCA1 or SCA3, their genes for ATAXIN1 or ATAXIN3 have a CAG expansion, so the genetic message molecules made from these genes can also be targeted by VO659. This means that if VO659 works to lower HTT levels in HD, it has the potential to help people with these other conditions too by lowering ATAXIN1 and 3 as well.

A basket trial: testing one drug in multiple diseases at once

Because VO659 targets the CAG repeat rather than something specifically unique to HTT, Vico designed what’s known as a “basket trial”. This is a clinical trial that tests a single drug in people with multiple different diseases that share a molecular similarity. In this case, people with HD, SCA1, and SCA3 are all enrolled in the same trial because all diseases are caused by a CAG expansion.

Basket trials are particularly valuable for rare diseases. HD affects roughly 1 in every 4,000 people, while SCA1 and SCA3 are even rarer, each affecting around 1 in 100,000. Recruiting enough participants for entirely separate trials in each disease would take considerable time and resources. 

By grouping participants together, Vico can more efficiently assess how safe and effective VO659 might be across all three conditions simultaneously, potentially speeding up the path to treatments for all of them.

This new fourth arm moves to a much less frequent schedule: just two doses per year, once every six months.

What’s new: a twice-yearly dosing arm

Earlier arms of the trial tested three different doses of VO659 – 10 mg, 20 mg, and 40 mg – given once every four weeks for a total of four doses. 

This new fourth arm moves to a much less frequent schedule: just two doses per year, once every six months. This is possible because VO659 appears to linger in the body for a long time after it’s administered, what scientists call a long half-life, meaning the drug may keep working well after a single dose. In this fourth cohort, Vico is testing the 2 highest doses of their drug – 20 mg and 40mg.

Participants in this new arm will be followed for 12 months to assess safety and tolerability at this reduced dosing frequency. The team will also be conducting pharmacokinetic and pharmacodynamic studies. These studies are a way of carefully tracking how the body handles the drug, including how much is absorbed, how it distributes through the body, how the body breaks it down, and how it eventually leaves the body. 

Why the switch up? 

Although not explicitly mentioned in their press release, we can speculate that this change in dosing schedule for VO659 is probably to improve the safety profile of this drug in people. In their previous update in late 2024, we learned that while VO659 was working to lower HTT levels as it was designed to do, it also seemed to be causing some significant side effects in participants in this part of the trial. 

Of the 6 people with HD who were given the drug, 1 person experienced radiculitis, a condition characterized by inflammation of certain nerve cells that can lead to painful sensory changes or motor weakness in the lower body and legs. Two people in the SCA1 group and 1 person in the SCA3 group also experience radiculitis. Fortunately, 3 of the 4 people who experienced this side effect showed signs of recovering as per Vico’s previous update. 

Radiculitis is a side effect that has been observed in studies investigating other ASO therapies. Vico stated at the time that they planned to mitigate this issue moving forward by lowering the amount of drug given to people in the trial, so this new dosing regimen is likely designed to address this issue.

Coming soon to the U.S.

Until now, the trial has been conducted entirely in Europe. But Vico also announced on February 24th that they’ve received clearance from the U.S. Food and Drug Administration (FDA) for what’s called an Investigational New Drug (IND) application. This is essentially the green light to begin clinical testing in the United States. 

The company stated that they plan to initiate U.S.-based trials for VO659 later this year, expanding the reach of this program to participants on this side of the Atlantic.

We previously reported on interim data from this trial showing a 38% reduction in expanded HTT protein levels in people with HD receiving the highest dose. However, this was only for 3 people, which is a very small number. We’ll continue to follow VO659’s progress as the trial moves forward.

Summary

• VO659 is an ASO drug delivered by spinal injection that targets the CAG repeat expansion underlying HD, SCA1, and SCA3
• It’s being tested in a “basket trial”, which is a single trial enrolling people with all three diseases at once. This helps speed up research in these rare conditions
• A new fourth arm of the ongoing Phase 1/2a trial has begun, testing a twice-yearly dosing schedule (compared to once every four weeks in earlier arms)
• Participants in this new arm will be followed for 12 months to assess safety, tolerability, and how the body processes the drug
• Vico has received FDA clearance to begin U.S.-based clinical trials for VO659 later this year