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

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

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.

One comment

  1. Kevin Wilkinson says:

    Is TCE the new Agent Orange, according to National Academy of Sciences, and ASTDR, yes via Camp Lejeune assessments.
    The contaminated water of Camp Lejeune is not the only known source of TCE exposure among US Military members.

    The GW IOM vol 2 APPENDIX D, the DOD/RAND, compiled list of ingredients constituting the toxic soup or cocktail of Gulf War, includes TCE and PCE as well as the other Camp Lejeune offenders.

    The VA website also determined that TCE is a frequent occupational exposure for many US Military members.

    I would assume a large portion of these exposures are due to the repair duties of our highly mechanized military, especially given that TCE is commonly found in cleaners and degreasers.

    TCE, is also found in products of the fire suppressant variety such as fire fighting foam.

    Or at least this is the source of potential TCE and cause of YOPD in a former USAF firefighter I was fortunate enough to encounter on line.

    I also encountered another heavy equipment mechanic such as myself, although he was still active duty, and in the process of medical separation for PD who confirmed the use of TCE currently.

    I also encountered another GW veteran with YOPD, who believes the source of his TCE exposures was by the munitions cleaning products that are supplied by the military and supports such theory with DOD documentation showing TCE as the product used.

    I have also encountered another former USAF member who recalls using TCE by the 55gal drum during his aircraft repair duties, including spraying into the engine and then being engulfed in the fumes caused by doing so.

    The VA still contends that we GW veterans are still to young to have PD, as implied by the words of the GW IOM vol 10.

    I do however have proof via email that Dr Higgins the National Director of Neurology concurs that the signs and symptoms of Gulf War Illness or other common name as described in the GW IOM vo 2 Chapter 7, as potential PD symptoms, I know that the signs and symptoms described exactly match the same signs and symptoms that the MDS at the DALLAS VAMC confirmed as YOPD for me. I was only 40 at the time of this two years ago.

    This same highly regarded MDS also is very sincere in her belief that TCE and PCE are actually components of Agent Orange, I have read some reports of the same or similar metabolites, but who am I as a lay person to determine that.

    I do know that the research by Samuel Goldman used as the basis for the determinations regarding Camp Lejeune by the NAS and ASTDR is highly regarded an indicates a much higher OR than any assessment of Agent Orange. This same research also shows the mechanisms associated with PD.

    This is the very reason cited by the NAS and ASTDR as the most important part of their assessment.

    This is also found to be consistent with the VA PD CONSORTIUM PUBLICATION, by Jeff Bronstein and associates, titled How to prove that pesticides cause Parkinson’s Disease.

    The ASTDR however also added PD as an occupational health risk of TCE using VA commissioned research by Dr. Zaheer as the rationale for determining such.

    I have extensive amounts of related documentation including from the manufacturer CRC INDUSTRIES, of the product BRAKLEEN 05089, which I personally used daily in the USAF,confirmed by my supervisor and associates of the time. This documentation known as the MSDS, again supplied by the manufacturer as confirmed for the applicable time frame, to contain >90% by volume TCE and or PCE, this product is still available today and can be purchased at Wal-Mart in the automotive section.

    I know that the VA will grievously continue to deny numerous veterans the benefits that they have earned and deserve until such time as that enough demand differently will you help me to share this matter to bring about awareness, please remember a substantial number of Gulf War veterans still remains undiagnosed and even worse often told it’s all in your head, if only they knew how wrong that is and correct at the same time, they may at least find some benefit in being given the correct medication.

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