DetailsCategory: DNA RNA and CellsPublished on Saturday, 12 September 2020 14:07Hits: 360

-- Data for Investigational Gene Therapy Treatment NBIb-1817 (VY-AADC) Presented at the MDS Virtual Congress 2020 --

- NBIb-1817 Treatment Showed Sustained Improvement in Motor Function, Including Greater "On" Time without Troublesome Dyskinesia and Reduction in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Scores, and Reduction in the Amount of Medications Up to Three Years in Patients with Parkinson's Disease

- 14 of 15 Patients Treated with NBIb-1817 Continued to Experience an Improvement in Disease Staging after Three Years, as Assessed by the Modified Hoehn & Yahr Scale

- Re-Initiation of Enrollment in Registrational RESTORE-1 Clinical Trial of NBIb-1817 Planned for Later this Year

SAN DIEGO, CA and CAMBRIDGE, MA, USA I September 11, 2020 I 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 1216, 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).

About Parkinson's Disease and NBIb-1817 (VY-AADC) Parkinson's disease is a chronic, progressive and debilitating neurodegenerative disease that affects approximately one million people in the U.S. and six million people worldwide. It is characterized by a loss of dopamine and 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. Dopamine is a chemical "messenger" that is produced in the brain and is involved in the control of movement. It is made when AADC converts the chemical levodopa to dopamine. As Parkinson's disease progresses, there is less AADC enzyme in parts of the brain where levodopa is converted to dopamine.

NBIb-1817 is an investigational recombinant adeno-associated viral (AAV) 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. NBIb-1817 is administered into the brain using intraoperative monitoring with magnetic resonance imaging (MRI)-facilitated targeted delivery.

About the RESTORE-1 Clinical TrialPaused temporarily in April 2020 due to the COVID-19 pandemic, Neurocrine Biosciences and Voyager Therapeutics plan to re-initiate RESTORE-1, a Phase 2, randomized, placebo-surgery controlled, double-blinded, multi-center clinical trial, to evaluate the safety and efficacy of NBIb-1817 in patients who have been diagnosed with Parkinson's disease for at least four years and have at least three hours of "Off" time during the day as measured by a validated self-reported patient diary.

For more information about the RESTORE-1 clinical trial, including eligibility criteria, please visit clinicaltrials.gov and restore1study.com.

About the RESTORE-2 Clinical TrialPreparations are ongoing for the RESTORE-2 global registrational trial that will include clinical sites within and outside the U.S.

About Neurocrine Biosciences and Voyager Therapeutics Strategic CollaborationIn 2019, Neurocrine Biosciences and Voyager Therapeutics entered into a strategic collaboration focused on the development and commercialization of gene therapy programs, VY-AADC for Parkinson's disease and VY-FXN01 for Friedreich's ataxia, as well as rights to two programs to be determined. This collaboration combines Neurocrine Biosciences' expertise in neuroscience, drug development and commercialization with Voyager's innovative gene therapy programs targeting severe neurological diseases.

About Neurocrine BiosciencesNeurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with 28 years of experience discovering and developing life-changing treatments for people with serious, challenging and under-addressed neurological, endocrine and psychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, Parkinson's disease, endometriosis* and uterine fibroids*, with three pivotal and five mid-stage clinical programs in multiple therapeutic areas. Headquartered in San Diego, Neurocrine Biosciences specializes in targeting and interrupting disease-causing mechanisms involving the interconnected pathways of the nervous and endocrine systems. For more information, visit neurocrine.com, and follow the company on LinkedIn. (*in collaboration with AbbVie)

About Voyager TherapeuticsVoyager Therapeutics is a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases. Voyager is committed to advancing the field of AAV gene therapy through innovation and investment in vector engineering and optimization, manufacturing, and dosing and delivery techniques. Voyager's wholly owned and partnered pipeline focuses on severe neurological diseases for which effective new therapies are needed, including Parkinson's disease, Huntington's disease, Friedreich's ataxia, and other severe neurological diseases. For more information on Voyager, please visit the company's website at http://www.voyagertherapeutics.com or follow @VoyagerTx on Twitter and LinkedIn.

SOURCE: Voyager Therapeutics

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