Neurocrine Biosciences and Voyager Therapeutics announce positive phase 1 results of genetic therapy for Parkinsons disease.

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  • Results Confirm the Posterior Trajectory as an Additional Surgical Delivery Route for VY-AADC in Patients with Parkinson’s Disease
  • Treatment with VY-AADC Improved Good ON Time (ON Time Without Troublesome Dyskinesia) by 1.7 Hours and Reduced OFF Time by 2.2 Hours at 12 Months in Patients with Parkinson’s Disease

SAN DIEGO, CA and CAMBRIDGE, MA, USA I May 05, 2019 I Neurocrine Biosciences, Inc. (NASDAQ: NBIX) and Voyager Therapeutics, Inc. (NASDAQ: VYGR) today announced Phase I trial results for VY-AADC from eight patients with Parkinson’s disease who participated in the open-label trial to evaluate the safety and efficacy of VY-AADC and to further assess the posterior (i.e., from the back of the head) surgical delivery approach. These Phase I results are being presented today as a poster presentation at the 2019 American Academy of Neurology (AAN) Annual Meeting. Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disorder that affects approximately one million people in the U.S ( per the Michael J Fox Foundation )

Treatment with VY-AADC improved good ON time (ON time without troublesome dyskinesia) by 1.7 hours from baseline and reduced OFF time by 2.2 hours at 12 months from baseline in patients with Parkinson’s disease. Exploratory analyses in four of the eight patients with low or no dyskinesia or absence of impulse control disorder (ICD) at baseline demonstrated a greater improvement in motor function including a 3.2-hour improvement in good ON time from baseline to 12 months. Infusions of VY-AADC were well tolerated with no serious adverse events (SAEs) reported. These Phase I results show that the posterior trajectory is an additional surgical delivery route in patients with Parkinson’s disease.

“The results from this Phase I trial in patients with Parkinson’s disease provide further evidence that VY-AADC administration can allow neurons in the brain to convert levodopa to dopamine and improve motor function,” said Eiry Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. “The results from this trial confirm previous data from a separate, ongoing Phase I study demonstrating that increased coverage of the putamen with VY-AADC leads to an increase in AADC enzyme activity and improvements in motor function and quality of life in patients with Parkinson’s disease – with less need for oral levodopa medication.”

VY-AADC Motor Function Results from the Phase I (PD-1102) Trial

The PD-1102 trial includes eight patients with advanced Parkinson’s disease. On average, patients’ baseline characteristics in PD-1102 were consistent with patients’ baseline from a separate, ongoing Phase Ib trial (PD-1101) employing a frontal (i.e., from the top of the head) surgical delivery approach. Two patients in PD-1102 were identified as having impulse control disorder while no patients were identified as having impulse control disorder in PD-1101. At baseline, patients’ mean good ON time was 9.1 hours and mean OFF time was 6.8 hours.  

Administration of VY-AADC with the posterior trajectory resulted in a mean coverage of the putamen of 54% and reduced the infusion time by approximately two hours (from 5.2 hours to 3.1 hours) compared to PD-1101. In PD-1102, treatment with VY-AADC increased AADC enzyme activity in the putamen as measured by positron emission tomography (PET) using [18F] fluorodopa (or 18F-DOPA) by 85%. AADC enzyme activity in the putamen as measured by PET using 18F-DOPA reflects the capacity of neurons in the brain to convert levodopa to dopamine. 

Treatment with VY-AADC improved patients’ motor function from baseline to twelve months across multiple assessments. These assessments include patient self-reported diary entries of ON and OFF times (including good ON time), Unified Parkinson’s Disease Rating Scales, and activities of daily living measures. In addition, patients’ reported an ability to maintain motor function with less Parkinson’s disease medication, as patients’ reported a mean 28% reduction in the dosage of Parkinson’s disease medication (measured as levodopa equivalents) at six months and at 12 months from a baseline mean of 1,500 mg/day.

Treatment with VY-AADC improved patients’ good ON time by 1.7 hours from baseline and reduced OFF time by 2.2 hours from baseline to 12 months. Exploratory analyses in PD-1101 suggested that patients with high dyskinesia or an ICD at baseline may show different outcomes, especially in patient-reported diary measures. A clinical assessment of the subgroup of patients (n=4) with no or low baseline dyskinesia as measured by the Unified Dyskinesia Rating Scale score (≤ 30) and absence of ICD at baseline as determined by the investigator, indicated that VY-AADC improved good ON time from baseline by 3.2 hours and reduced OFF time by 3.2 hours in patients at 12 months.

In addition to motor function, VY-AADC improved patients’ quality of life as measured by the patient-reported 39-item Parkinson’s Disease Questionnaire (PDQ-39). For PDQ-39, VY-AADC improved (reduced) patients’ score by a mean change from baseline to 12 months of -7.6. Infusions of VY-AADC have been well tolerated in the eight patients treated in PD-1102 with no serious adverse events (SAEs) reported.

About the Phase II RESTORE-1 Clinical Trial
Based on the results from PD-1101 and PD-1102, Voyager initiated RESTORE-1, a Phase II, randomized, placebo-surgery controlled, double-blinded, multi-center, clinical trial to evaluate the safety and efficacy of VY-AADC in patients who have been diagnosed with Parkinson’s disease for at least four years, are not responding adequately to oral medications, 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 restore1study.com.

About Neurocrine Biosciences and Voyager Therapeutics Strategic Collaboration
In the first quarter of 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 Parkinson’s Disease and 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. Parkinson’s disease is characterized by a loss of dopamine and its function. Dopamine is a chemical “messenger” that is produced in the brain and is involved in the control of movement. Dopamine is made in the brain when the enzyme AADC (Aromatic l-amino acid decarboxylase) converts the chemical levodopa to dopamine. Levodopa, AADC, and dopamine are each present at normal levels in healthy people. As Parkinson’s disease worsens, there is less AADC enzyme in parts of the brain where it is needed to convert levodopa to dopamine. When this happens, patients’ motor function may worsen with a less predictable response to medications.

VY-AADC, an investigational gene therapy, is designed to put the AADC enzyme into brain cells where it can convert levodopa to dopamine. To do this, the AADC gene is delivered inside a transporter called “adeno-associated viral vector” (AAV). Interim results from an open-label Phase Ib trial demonstrated that administration of VY-AADC to the putamen using intraoperative monitoring with MRI facilitated targeted delivery of the investigational gene therapy with dose-dependent increases in AADC enzyme expression and improvements in clinical measures and has been well-tolerated to date.

This article was republished and edited for brevity using materials from Neurocrine’s press release.