First person dosed in trial of VO659 targeting Huntington’s genetic cause

Drug expected to also be effective for other CAG repeat expansion diseases

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A Phase 1/2a clinical trial testing VO659, Vico Therapeutics’ experimental therapy, in people with Huntington’s disease and other hereditary neurological disorders caused by a similar type of mutation has dosed the first patient.

“We are encouraged by the continued progress of our development program and very pleased to announce the first patient dosed in this Phase 1/2a study of VO659,” Scott Schobel, MD, chief medical officer at Vico, said in a company press release.

Huntington’s disease is caused by excessive repeats of a portion of DNA, called CAG triplets, within the HTT gene, which provides instructions for making the huntingtin protein. This specific genetic defect results in the production of an abnormally long huntingtin protein, which is thought to be toxic and drive disease progression.

VO659 is a type of molecule called an allele-preferential antisense oligonucleotide (ASO). It is designed to bind to CAG triplets in a gene’s messenger RNA (mRNA), preventing it from being translated into the abnormally long protein. mRNA is the intermediate molecule derived from DNA that serves as a template in protein production.

According to Vico, VO659 is expected to be effective for Huntington’s and other CAG repeat expansion diseases (also sometimes called polyglutamine or polyQ diseases) that are caused by excessive CAG triplets in a gene.

“VO659 is the first allele-preferential ASO in clinical development with broad application to all CAG repeat expansion diseases,” Schobel said. “The robust preclinical data package for VO659 demonstrates favorable brain uptake, potency and durability of effect, and we look forward to assessing the translation of these characteristics in this clinical trial.”

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Treatment may lead to reduction in levels of abnormally long proteins

Preclinical studies in models of Huntington’s and two other CAG repeat expansion diseases called spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3) have suggested VO659 treatment can reduce levels of the abnormally long proteins that drive these disorders, according to Vico.

SCA1 and SCA3 are caused by CAG repeat expansions in the ATXN1 and ATXN3 genes, respectively.

VO659 received orphan drug designation in the U.S. and Europe for the treatment of Huntington’s, as well as for SCA. This status is meant to accelerate the therapy’s clinical development and regulatory review.

The ongoing multi-center Phase 1/2a clinical trial aims to enroll up to 71 people with early manifest Huntington’s, SCA1, or SCA3. Participants will receive multiple doses of VO659 via an injection through the spine, called an intrathecal injection.

The study’s main goal is to assess the experimental therapy’s safety and tolerability. Exploratory goals include the effect of treatment on levels of disease-driving proteins and markers of nerve damage.

“It is our mission to bring safe, effective therapies to patients and families affected by devastating neurological diseases, and today marks an important milestone in our journey to realize this mission,” said Micah Mackison, Vico’s CEO. “We are grateful to the trial investigators and patients participating in our Phase 1/2a study as we assess the potential of VO659 in [Huntington’s disease], SCA1 and SCA3.”

The company plans to present the trial’s design, along with positive preclinical data of VO659, at the CHDI Foundation‘s 18th Annual Huntington’s Disease Therapeutics Conference, to be held April 24-27 in Dubrovnik, Croatia.