Voyager Recruits Patients for Phase 1 Trial Testing VY-AADC01 Gene Therapy Delivery

Catarina Silva, MSc avatar

by Catarina Silva, MSc |

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Voyager Therapeutics announced it’s recruiting participants for the company’s new Phase 1 clinical trial to test a new approach for their gene therapy VY-AADC01 in Parkinson’s disease patients. The company has also released updates to its ongoing Phase 1b trial testing VY-AADC01 and highlighted its preclinical programs focusing on amyotrophic lateral sclerosis, Huntington’s disease, and Friedreich’s ataxia.

AAV is a small virus capable of infecting human and primate cells. Of the commonly used viruses, AAV produces the lowest immune response and does not cause disease, constituting a promising method for gene therapy.

Voyager’s VY-AADC01 delivers the AADC gene, which codes for an enzyme called l-amino acid decarboxylase (AADC) and mediates the conversion of levodopa into dopamine, directly into a specific brain area of advanced Parkinson’s patients. Death of dopaminergic neurons and a reduction in AADC enzyme levels are two fundamental mechanisms underlying Parkinson’s disease. With VY-AADC01, researchers aim to restore the conversion of levodopa, thus increasing dopamine production.

The company’s ongoing VY-AADC01 Phase 1b trial (NCT01973543) demonstrates durable, dose-dependent, and time-dependent improvements across multiple measures of patients’ motor function after a one-time administration, using significantly lower doses of oral levodopa.

“Based on these attributes, neurologists indicated an interest to recommend VY-AADC to patients even before they reach an advanced stage of disease,” Steve Paul, MD, president and chief executive officer of Voyager Therapeutics, said in a press release.

These results were presented last month at the Congress of the European Society of Gene and Cell Therapy in Berlin.

Now, Voyager launched a new Phase 1 trial (NCT03065192) that is currently recruiting participants and is designed to further optimize the intracranial delivery of VY-AADC01. The therapy is administered in a single-dose infusion using a posterior trajectory into the patient’s putamen — a large structure in the brain filled with dopamine receptors — guided by magnetic resonance imaging (MRI).

Until now, six patients had received VY-AADC01 with this posterior approach, which has been well-tolerated with no serious adverse events. The new delivery approach increased the coverage area reached by VY-AADC01 in the patients’ putamen by approximately 50% and reduced the surgery time by up to three hours compared to the transfrontal approach used in the ongoing Phase 1b trial.

The trial’s primary outcomes will evaluate changes in several parameters from baseline compared to three years after therapy administration, including the number of adverse and serious adverse events and change in Columbia-Suicide Severity Rating Scale (C-SSRS) results. Additionally, researchers will assess VY-AADC01’s safety by any clinically significant abnormalities on MRI scans compared to baseline, along with routine physical and laboratory tests.

Voyager will continue to follow patients in the Phase 1b trial (NCT01973543) and in the new Phase 1 trial (NCT03065192) and expects to update the trial’s results by April 2018.

The company remains on track to file an investigational new drug (IND) application for Parkinson’s management before the end of 2017.

Voyager aims to enroll more patients in this ongoing trial before starting their pivotal Phase 2-3 program, which is set to begin dosing its first patient in the second quarter of 2018.

Regarding the study of other nervous system diseases, the pharmaceutical company also has ongoing preclinical trials focused on the impact of new AAV gene therapy capsids and virus delivery optimization in amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Friedreich’s ataxia. All of these trials show promising results.

Voyager intends to identify a lead clinical candidate for the treatment of Friedreich’s ataxia during 2018 and expects to file two IND applications from these programs by 2019.