FDA Gives Go-ahead for Phase 1/2 Trial Testing VY-HTT01 Gene Therapy

Marisa Wexler MS avatar

by Marisa Wexler MS |

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The U.S. Food and Drug Administration (FDA) has granted Voyager Therapeutics permission to start a clinical trial testing VY-HTT01, its investigational gene therapy for Huntington’s disease.

Voyager is planning to launch the Phase 1/2 clinical trial, called VYTAL, later this year.

VYTAL will be a dose-escalation study, meaning that enrolled participants will be given one of multiple increasing doses of the therapy candidate. The main goal of the trial will be to assess the safety and tolerability of VY-HTT01 in people with early manifest Huntington’s. Clinical outcome measures and biological markers of disease also will be assessed.

An investigational new drug (IND) application — which seeks regulatory approval to launch a clinical trial and must be cleared by the FDA before a study can start — had been submitted by Voyager last September. However, the FDA had put the application on hold due to issues with VY-HTT01’s chemistry, manufacturing, and controls.

That hold now has been lifted following a comprehensive review by the FDA of information previously submitted.

“The decision by the FDA regarding our IND application for VY-HTT01 for Huntington’s disease represents an important milestone for Voyager and is the result of years of commitment to developing an impactful new therapy to address this devastating disease,” Andre Turenne, president and CEO of Voyager, said in a press release.

Huntington’s disease is caused by an abnormal form of the protein huntingtin (HTT), due to mutations in the gene of the same name. When cells “read” the HTT gene to make the HTT protein, a molecule called messenger RNA, or mRNA, is made in an intermediate step between gene “reading” and protein production. This mRNA is then sent to the cell’s protein-making machinery so a protein can be produced.

VY-HTT01 is a gene therapy that works by using an engineered viral vector to deliver a small RNA molecule, called microRNA, into a patient’s cells. The microRNA can target the mutant HTT mRNA, which prevents the toxic HTT protein from being made.

Prior research in large non-human primates has shown that surgically delivering the gene therapy to specific parts of the brain can substantially reduce levels of HTT protein and mRNA. The therapy also has shown a positive safety profile in preclinical animal studies.

“Our investigational gene therapy has been designed to achieve broad knockdown of HTT mRNA throughout the brain via a one-time MRI-guided neurosurgical delivery,” said Omar Khwaja, chief medical officer and head of research and development at Voyager.

“We are thrilled to be collaborating with leading experts in Huntington’s disease and neurosurgical delivery of gene therapies as we begin the planned clinical evaluation of our promising candidate,” Khwaja added.