Benzinga | Sep 11, 2020 11:34AM EDT

Neurocrine Biosciences, Voyager Therapeutics Highlight Presentation Of New Long-Term, 3-Year Data Showing 1-Time Treatment with an Investigational Gene Therapy Showed Sustained Improvement in Motor Function in Patients with Parkinson's Disease

Neurocrine Biosciences, Inc. (NASDAQ:NBIX) and Voyager Therapeutics, Inc. (NASDAQ:VYGR) today announced data from PD-1101, a Phase Ib open-label, three-year efficacy and safety study, demonstrating that a one-time treatment with investigational gene therapy, NBIb-1817 (VY-AADC), showed sustained improvement in motor function including greater "On" time without troublesome dyskinesia, reduction in Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, and reduction in the amount of medications in patients with Parkinson's disease. In the PD-1101 study, NBIb-1817 reduced average "Off" time by up to -1.91 hours and improved average "On" time without troublesome dyskinesia by up to +2.23 hours in patients with advanced Parkinson's disease after three years across three cohorts. In addition, 14 out of 15 patients treated with NBIb-1817 continued to show an improvement in disease staging after three years, as assessed by the modified Hoehn & Yahr scale. These new data, along with two-year data from another open-label Phase Ib trial, PD-1102, were presented today at the MDS Virtual Congress 2020, September 12--16, 2020 (www.mdscongress.org/Congress/Registration.htm).



In data from the three-year PD-1101 trial, the one-time treatment with NBIb-1817 showed sustained reduction in diary "Off" time by an average of -0.15 to -1.91 hours (baseline 4.28 to 4.93 hours) and improved diary "On" time without troublesome dyskinesia by an average of +0.26 to +2.23 hours (baseline 10.32 to 10.46 hours) across the cohorts as reported by 15 patients with advanced Parkinson's disease. NBIb-1817 also showed sustained improvement in motor function after three years, as measured by UPDRS Part III off medication scores, by -10.2 to -19.0 points (baseline 35.8 to 38.2 points) across the cohorts, per clinician assessment. Requirements for Parkinson's disease medications were also reduced in cohorts 2 and 3 (daily levodopa-equivalent dose reductions, average of -322.0 and -441.2 mg/day, respectively; baseline 1507.0 and 1477.0 mg/day, respectively). Two-year data from the PD-1102 trial for 7 patients showed that NBIb-1817 reduced diary "Off" time by an average of -3.2 hours and increased diary good "On" time by +2.1 hours (baselines 9.3 hours and 6.6 hours, respectively). In this study, NBIb-1817 showed sustained improvement in motor function after two years, with improved UPDRS Part III off medication scores of -12.0 points (baseline 34.4). Requirements for Parkinson's disease medications were also reduced (daily levodopa-equivalent dose reduction, average of -439.5 mg/day; baseline 1500.9 mg/day). Preliminary safety data from both studies suggest that NBIb-1817 was well-tolerated, with no study drug-related serious adverse events (SAEs) reported. The most common adverse events reported were headache, hypoesthesia, and musculoskeletal pain (PD-1101), and upper respiratory tract infection, headache, nausea, and depression (PD-1102).

"It is promising to see that after three years, a single administration of one-time investigational gene therapy treatment NBIb-1817 showed sustained reduction in 'Off' time, as well as improvement in 'On' time without troublesome dyskinesia and other measures of motor function in patients with Parkinson's disease," said Chad Christine, M.D., primary author, a lead investigator of the study and Professor of Neurology at the University of California, San Francisco (UCSF) Weill Institute for Neurosciences. "Parkinson's disease patients' motor function would be expected to worsen over three years, making these results very encouraging. The standard of care for advanced Parkinson's disease has not significantly changed in decades and it is our hope that NBIb-1817 has the potential to become the first gene therapy for Parkinson's disease."

Parkinson's disease is a chronic, progressive and debilitating neurodegenerative disorder that affects approximately one million people in the U.S. and six million people worldwide. It is characterized by a loss of dopamine from neuronal degeneration, with a concomitant loss of the aromatic L-amino acid decarboxylase (AADC) enzyme required to synthesize dopamine in the brain, leading to associated impairment in motor, neuropsychiatric, and autonomic functions.

"We are pleased that the results from these studies show that one-time treatment with investigational NBIb-1817 may help restore the brain's ability to convert levodopa into dopamine," said Eiry Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "Our hope is that NBIb-1817 will help patients experience less 'Off' time and more 'On' time and improve motor symptom control. We plan to re-initiate enrollment in our registrational RESTORE-1 clinical trial with NBIb-1817 this year and look forward to further evaluating NBIb-1817 in patients with Parkinson's disease."

NBIb-1817 is an investigational recombinant adeno-associated viral serotype 2 vector encoding the gene for human AADC that is designed to help produce the AADC enzyme in brain cells where it can convert levodopa to dopamine.

"We are encouraged by the congruence of long-term data, including clinician- and patient-reported clinical outcomes in our clinical studies," said Omar Khwaja, M.D., Ph.D., Chief Medical Officer and Head of Research and Development at Voyager Therapeutics. "These results are promising and show that the approach has the potential to transform the treatment of Parkinson's disease, and help improve the lives of patients and their families."

Additional information about PD-1101 and PD-1102 will be available on demand for registered participants through October 1, 2020 on the MDS meeting website (www.mdscongress.org/Congress/Registration.htm).

* Christine CW, Richardson RM, Van Laar AD, et al. Three-Year Safety and Clinical Outcomes from the PD-1101 Trial of AADC Gene Therapy for Advanced Parkinson's Disease Poster # 879: Update on Genetics of Movement Disorders, September 13, 2020, 10:30--12:30pm EST (10-minute prerecorded presentation)

* Factor SA, Van Laar AD, Richardson RM, et al. AADC Gene Therapy Administered via a Posterior Approach: 24-Month Results from the PD-1102 Trial in Advanced Parkinson's Disease Poster # 889: Poster Tour, launches on-demand on September 11, 2020 8:00am EST (5-minute prerecorded presentation)