In preclinical data, VY-HTT01 showed a robust and durable reduction of huntingtin mRNA and protein while distributed across core areas of Huntington disease pathology.
Voyager Therapeutics has received FDA clearance for its investigational new drug (IND) application for VY-HTT01, a gene therapy candidate for the treatment of Huntington disease (HD), and may proceed with its planned phase 1/2 clinical trial, according to a recent announcement.1
Voyager submitted the IND for the drug in September of 2020 and was notified a month later that it had been placed on clinical hold pending the resolution of certain chemistry, manufacturing, and controls (CMC) matters.2 Upon full comprehensive review of those CMC matters, the FDA felt as though the company could proceed. The trial, named VYTAL (no NCT number available yet), is a dose-escalation study to evaluate the safety and tolerability of VY-HTT01 in patients with early manifest HD and is set to be initiated this year.
"The decision by the FDA regarding our IND application for VY-HTT01 for Huntington 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 chief executive officer, Voyager, said in a statement.1
The gene therapy is comprised of an adeno-associated virus capsid (AAV1) designed to reduce the expression of huntingtin (HTT), thereby altering disease progression. It is also comprised of a proprietary transgene that harnesses the canonical RNA interference pathway to selectively knock down levels of HTT messenger RNA (mRNA).
At the 2018 Congress of the European Society of Gene and Cell Therapy (ESGCT), the company revealed that VY-HTT01 reduced HTT mRNA on average by 68% in the caudate, 67% in the putamen, 73% in the thalamus, and 32% in the cortical neurons among adult non-human primates.3
"Our investigational gene therapy has been designed to achieve broad knockdown of HTT mRNA throughout the brain via a 1-time MRI-guided neurosurgical delivery,” Omar Khwaja, MD, PhD, chief medical officer and head of Research and Development, Voyager, said in a statement.1 “We are thrilled to be collaborating with leading experts in Huntington disease and neurosurgical delivery of gene therapies as we begin the planned evaluation of our promising candidate.”
HD is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor, cognitive, and behavioral functions. Currently, there are no FDA-approved treatments targeting the underlying cause of the disease.
The positive news of VT-HTT01 and its future phase 1/2 study comes shortly after the HD community recently learned that 3 promising HD investigational treatments were being terminated from their respective clinical programs.
In March, Wave Life Sciences announced that the results from its phase 1b/2a PRECISION-HD2 and PRECISION-HD1 trials did not suggest that the clinical development of WVE-120102 and WVE-120101, 2 agents that targeted the single nucleotide polymorphisms (SNPs) SNP1 and SNP2.4 Days later, Roche announced that tominersen, the first agent to successfully target and reduce levels of mutant HTT protein in patients with HD, will discontinue dosing.5
NeurologyLive recently published episode 34 of the Mind Moments podcast, which featured Daniel Claassen, MD, MS, director, Huntington’s Disease Clinic, and division chief, Behavioral and Cognitive Neurology, Vanderbilt University Medical Center. He sat down to discuss the recent news of the trial program terminations, and the hope that remains in the HD pipeline despite these setbacks.