Phase 1 Study of Voyager’s Gene Therapy Shows Potential for Parkinson’s Patients

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by Alice Melão |

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Voyager's gene therapy for Parkinson's

The latest result from Voyager Therapeutic’s Phase 1 clinical trial on gene therapy (VY-AADC01) for advanced Parkinson’s disease shows early promise for the improvement of motor functions and quality of life of patients.

These data were presented as part of an emerging oral presentation session at the 2017 Annual Meeting of the American Academy of Neurology (AAN) through April 28 in Boston, and at the American Association of Neurological Surgeons (AANS) Annual Scientific Meeting April 22-26 in Los Angeles.

“We are pleased that VY-AADC01 data were selected for oral presentation at major neurology and neurosurgery meetings,” Bernard Ravina, chief medical officer of Voyager Therapeutics, said in a press release.

Motor symptoms of Parkinson’s disease are mainly caused by degeneration of brain cells sensitive to a hormone called dopamine in a brain region called the substantia nigra. Most of advanced Parkinson’s patients present reduced levels of the enzyme AADC, which is responsible for the transformation of levodopa, or L-DOPA, into dopamine.

To overcome the defect of AADC levels in neurons, Voyager Therapeutics developed a targeted gene therapy to directly deliver and promote the expression of the enzyme in a brain region called the putamen. Because patients with advance Parkinson’s disease do not show degeneration of the dopamine-responsive neurons in this region, contrary to what is seen in the substantia nigra, promoting putamen neurons to transform L-DOPA to dopamine can potentially reduce Parkinson’s motor symptoms following a single administration.

The investigative therapy is currently being tested in a Phase 1 clinical trial (NCT01973543). Interim results from the study showed significant beneficial effects on improving patients’ motor skills. The latest results featured in the presentation entitled “Intraputaminal AADC gene therapy for advanced Parkinson’s disease: Interim Results of a Phase 1b Trial,” presented at the AAN annual meeting, continue to show the encouraging therapeutic effect of VY-AADC01.

A total of 10 patients with advanced Parkinson’s disease and disabling motor fluctuations received single bilateral injections of VY-AADC01 in the putamen region. Patients were separated into two groups and ascending doses of the treatment were tested.

Twelve months after treatment, it was possible to observe that the patients improved their motor function. Patients in lower-treatment dose cohort 1 showed a UPDRS-IV total score improvement of 1.2 points, and the higher-treatment dose cohort 2 presented 2.7 points improvement. In addition, according to patient-reported 39-item Parkinson’s Disease Questionnaire (PDQ-39) score results, the patients in cohort 2 reported an improvement of about 9.2 points.

This reported improvement led to a reduction of the daily oral levodopa standard care therapy of about 10 percent for cohort 1 and 35 percent for cohort 2.

“In addition to the previously reported improvements in biomarkers and motor symptoms, investigators at the AAN meeting presented data on patients’ improved function and quality of life,” Ravina said. “Here, we were encouraged with the 9-point improvement in PDQ-39 total score, a patient reported outcome, in Cohort 2 at 12 months.”

Data presented at the AANS meeting was an overview of the evolution of the real-time MRI-guided surgical procedure used during the clinical trial. The improvements made to the surgical procedure led to an increased coverage of the targeted brain region of 21% in cohort 1 and 34% in cohort 2.

Based on PET scans, the researchers confirmed that AADC expression and activity achieved after treatment and after surgical modifications were increased. Treatment was well-tolerated overall with no treatment-related severe adverse events reported.

“In addition to these data at the AAN meeting, the data at the AANS meeting highlighted key advances in the neurosurgical techniques used to administer VY-AADC01 and increase the coverage of the putamen, the brain region that we are targeting with our gene therapy approach aimed at restoring patients’ response to their levodopa medication,” Ravina said.

Voyager Therapeutics is evaluating VY-AADC01 gene therapy’s safety and effectiveness in Parkinson’s patients in another Phase 1 clinical trial (NCT01973543).

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