Lancet Neurology Publishes First Successful Phase 2 Study of Gene Therapy for Parkinson's Disease Patients
FORT LEE, N.J., March 16, 2011 /PRNewswire via COMTEX/ --
Neurologix, Inc. (OTC Bulletin Board: NRGX), announced today that the results of the Company's Phase 2 clinical trial for its novel, investigational gene therapy NLX-P101 for the treatment of Parkinson's disease (PD) were published in an online-first edition of The Lancet Neurology. The randomized, double-blind, sham surgery-controlled trial of 45 subjects with advanced PD met its primary outcome measurement for efficacy and demonstrated that NLX-P101 gene therapy was safe and well-tolerated over the six month blinded study period.
Study results show that NLX-P101 treatment led to a mean 23.1 percent improvement (8.1 points) in off-medication Unified PD Rating Scale (UPDRS) motor score at the six-month study end-point, compared to a mean 12.7 percent (4.7 points) improvement with sham treatment. Improved motor control in the NLX-P101 group was seen at one month and continued virtually unchanged throughout the blinded study period. The improvement in UPDRS motor scores from baseline in the NLX-P101 group was significantly greater than sham subjects over the six month study period (p=0.04).
Study results also show that 50% of subjects treated with NLX-P101 achieved previously defined moderate-to-large clinically-meaningful symptom improvements (> / = 9 points in UPDRS), compared to just 14% of subjects who received a sham surgical treatment (p=0.03). No serious adverse events (SAEs) related to the gene therapy or surgical procedure were reported.
"This is the first Phase 2 study conducted under a rigorous randomized, double-blind, sham-controlled surgical design to conclusively demonstrate that gene therapy can be effective for neurological diseases. This confirms our Phase I results and indicates that NLX-P101 may provide a safe, effective and minimally invasive treatment option for patients with PD," noted senior author and co-principal investigator Andrew Feigin, M.D. of The Feinstein Institute for Medical Research at North Shore - LIJ Health System in Manhasset, New York.
According to lead author and co-principal investigator Peter LeWitt, M.D., Director of Movement Disorders at Henry Ford Health System in West Bloomfield, Michigan, "Subjects in our study who received the NLX-P101 treatment displayed better motor performance and control of Parkinsonism than subjects who received sham surgery. This benefit occurred early and was long-lasting. The NLX-P101 study demonstrates that the promise of gene therapy for neurodegenerative disorders appears more likely to become a reality."
"Based on these data, we are more confident that NLX-P101 has great potential to advance the treatment paradigm for Parkinson's patients, and may offer an important, new therapy for patients with this debilitating disease," said Clark A. Johnson, President and Chief Executive Officer of Neurologix. "The publication of our Phase 2 study results by The Lancet Neurology is important validation for our work in gene therapy, which has been ongoing for over a decade. We are very proud of the high-quality science that has supported our program from the start and that rigorous peer-review has once again supported publication of our data in a top-tier journal. These results strongly support the establishment of a Phase 3 clinical trial of NLX-P101 in subjects with Parkinson's disease. We recently discussed our Phase 2 results with the FDA and plan to submit a Phase 3 protocol under a Special Protocol Assessment later this year."
This novel treatment approach was pioneered by Neurologix, Inc. scientific co-founders Matthew J. During, M.D., D.Sc., Professor of Molecular Virology, Immunology and Medical Genetics, Neuroscience and Neurological Surgery, The Ohio State Medical School, and Professor of Molecular Medicine and Pathology, University of Auckland, New Zealand, and Michael G. Kaplitt, M.D., Ph.D., Associate Professor and Vice-Chairman for Research, Dept. of Neurological Surgery, and Director, Stereotactic and Functional Neurosurgery, Weill Medical College of Cornell University. The two researchers have been at the forefront of gene therapy research since 1989 and the Phase 2 trial was the culmination of nearly 20 years of progress with their work in adeno-associated virus (AAV) gene transfer technology. They were the first to demonstrate that AAV could be an effective gene therapy agent in the brain, which they reported in their landmark Nature Genetics paper in 1994. Drs. During, Kaplitt and colleagues subsequently published additional research demonstrating the beneficial effects of AAV-GAD gene therapy for PD in the journal Science in 2002. The Company's Phase 2 study findings build upon earlier positive results from the NLX-P101 Phase 1 trial, which was the first ever clinical gene therapy trial for PD or any other adult neurological disorder. Results of that study appeared in 2007 as a cover article in The Lancet and in a second article in the Proceedings of the National Academy of Sciences.
About the Phase 2 Study
The trial, funded by Neurologix and led by Drs. Feigin and LeWitt with researchers from eight leading medical centers in the United States, involved 45 subjects with moderate to advanced PD who were not adequately controlled with current therapies. Medical centers that participated in the study included: Henry Ford Health System; Massachusetts General Hospital; Stanford University School of Medicine; The Feinstein Institute for Medical Research of the North Shore-LIJ Health System; The Ohio State University College of Medicine; University of ColoradoSchool of Medicine; University of Rochester School of Medicine; and Wake Forest University School of Medicine.
Study subjects were randomized to receive either NLX-P101 treatment or sham surgery. Subjects in the NLX-P101 treatment arm received infusions of the genetic material directly into bilateral subthalamic nuclei (STN), a key brain region involved in motor function. Sham-assigned subjects underwent simulation of a bilateral neurosurgical procedure. At the end of each procedure, infusion catheters were removed at the bedside and nothing was left in the brain. All procedures were performed under local anesthesia. All but one of the trial participants were discharged from the hospital within 48 hours after the surgical procedure.
Subjects were permitted to take PD medications, as long as they maintained unchanged dosages for at least one month prior to surgery. Subjects continued their PD medications throughout the six-month study and researchers were encouraged to minimize any dosage changes.
Subjects were evaluated for symptom improvement at baseline, one, three and six months following the procedure using the UPDRS Part 3 motor score. The primary outcome measure was the difference in UPDRS motor scores between NLX-P101 and sham-treated subjects, when the subjects were off PD medication. Other tests assessed motor fluctuations, constancy of medication effect and neuropsychological evaluations. The researchers defined a clinically-meaningful response based on a 25 percent mean improvement from the initial Phase 1 NLX-P101 study (9 - points), which corresponded to a moderate-to-large clinically-meaningful response in a recent independent study correlating quality of life improvements with UPDRS motor score changes in PD patients. Patients in the sham surgery arm of the study who continue to meet all eligibility requirements will be provided an opportunity to receive NLX-P101 in a planned cross-over study. Treated subjects continue to be evaluated in an open-label, long-term follow-up study.
Data from eight subjects (six NLX-P101, two sham) were excluded from analysis prior to unblinding, as defined by the protocol, due to failure to receive the treatment as indicated because of problems with the infusion device. This novel device, which was first used in human patients during this study, enables NLX-P101 to be infused outside of the operating room, and then removed easily at the bedside.
Additional Study Results
Several secondary measures also supported an improved outcome for NLX-P101 subjects. NLX-P101 treatment was associated with a significant improvement at six months in clinical impression of PD severity, compared to sham treatment (p=0.02). Additionally, the off-medication Global Rating of Parkinsonism (provided by a blinded rater) demonstrated significant differences between NLX-P101 and sham subjects (p=0.02).
In contrast to the sham treatment group, a higher percentage of NLX-P101 treated subjects reported consistent medication effects and a decreased percentage of subjects experienced "on-off" fluctuations and severe gait freezing episodes. Furthermore, there were no signs of deterioration in cognitive or other neuropsychological performance over the study period.
Adverse events (AEs) associated with the experimental procedure were mild and did not suggest unforeseen risks associated with bilateral STN infusions of NLX-P101. One SAE occurred during the six month blinded study period in the NLX-P101 group-- an episode of bowel obstruction occurred four months postoperatively. The SAE was unrelated to the NLX-P101 treatment or the surgical procedure and fully resolved.
A Novel Approach to Gene Therapy
NLX-P101 aims to reset the overactive brain cells in the STN to inhibit electrical activity and return brain network activity to more normal levels. In PD, the loss of dopamine-secreting neurons alters chemical signaling pathways in the brain such that input to the STN is altered. The therapeutic approach with NLX-P101 modulates the activity of the STN (which is overactive in PD) by restoring GABA, a neurotransmitter important in STN function. GABA is made by a gene called glutamic acid decarboxylase (GAD). NLX-P101 uses an AAV vector (a disabled, non-pathogenic virus) to deliver the GAD gene into the STN. Increasing GAD activity causes more GABA to be synthesized, thus helping to lessen the STN over-activity.
About Parkinson's disease
Parkinson's disease is a progressive and debilitating neurodegenerative disorder that arises from the gradual deterioration of nerve cells in the brain. It affects the control of bodily movement and is characterized by four principal features: limb tremor, limb rigidity, bradykinesia (slowness of movement) and postural instability (trouble with balance).
Parkinson's disease is typically a disease that affects people over the age of 50. According to the National Parkinson Foundation, 1 million Americans currently have PD, and an estimated 50,000 to 60,000 new cases are diagnosed each year in the United States. Standard therapy for PD often involves use of levodopa, a drug which stimulates production of dopamine. Unfortunately, many patients develop complications from this and other medications, or they can fail to be effective. An alternative treatment is electrical deep brain stimulation, which requires the implantation of permanent medical devices in the brain.
Neurologix, Inc. (OTCBB:NRGX), is a clinical-stage biotechnology company dedicated to the discovery, development, and commercialization of gene transfer therapies for serious disorders of the brain and central nervous system (CNS). Neurologix's therapeutic approach is built upon the groundbreaking research of its scientific founders and advisors, whose accomplishments have formed the foundation of gene therapy for neurological illnesses. The Company's current programs address such conditions as Parkinson's disease, epilepsy, depression and Huntington's disease, all of which are large markets not adequately served by current therapeutic options. For more information, please visit the Neurologix website at http://www.neurologix.net/.
Cautionary Statement Regarding Forward-Looking Statements
This news release includes certain statements of the Company that may constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and which are made pursuant to the Private Securities Litigation Reform Act of 1995. These forward-looking statements and other information relating to the Company are based upon the beliefs of management and assumptions made by and information currently available to the Company. Forward-looking statements include statements concerning plans, objectives, goals, strategies, future events, or performance, as well as underlying assumptions and statements that are other than statements of historical fact. When used in this document, the words "expects," "promises," "anticipates," "estimates," "plans," "intends," "projects," "predicts," "believes," "may" or "should," and similar expressions, are intended to identify forward-looking statements. These statements reflect the current view of the Company's management with respect to future events. Many factors could cause the actual results, performance or achievements of the Company to be materially different from any future results, performance or achievements that may be expressed or implied by such forward-looking statements, including, but not limited to, the following:
- The Company is still in the development stage and has not generated any revenues. From inception through September 30, 2010, it incurred net losses and negative cash flows from operating activities of approximately $58 million and $43 million respectively. Management believes that the Company will continue to incur net losses and cash flow deficiencies from operating activities for the foreseeable future. Because it may take years to develop, test and obtain regulatory approval for a gene-based therapy product before it can be sold, the Company likely will continue to incur significant losses for the foreseeable future. Accordingly, it may never be profitable and, if it does become profitable, it may be unable to sustain profitability.
- The Company will need to conduct future clinical trials for treatment of Parkinson's disease using NLX-P101. If the trials prove unsuccessful, future operations and the potential for profitability will be materially adversely affected and the business may not succeed.
- There is no assurance as to when, or if, the Company will be able to successfully receive approval from the FDA on its Investigational New Drug Application to commence a Phase 1 clinical trial for the treatment of epilepsy.
- There is no assurance as to when, or if, the Company will be able to successfully complete the required preclinical testing of its gene therapy for the treatment of depression or Huntington's disease to enable it to file an Investigational New Drug Application with the FDA for permission to begin a Phase 1 clinical trial or that, if filed, such permission will be granted.
Other factors and assumptions not identified above could also cause the actual results to differ materially from those set forth in the forward-looking statements. Additional information about factors that could cause results to differ materially from management's expectations is found in the section entitled "Risk Factors" in the Company's 2009 Annual Report on Form 10-K. Although the Company believes these assumptions are reasonable, no assurance can be given that they will prove correct. Accordingly, you should not rely upon forward-looking statements as a prediction of actual results. Further, the Company undertakes no obligation to update forward-looking statements after the date they are made or to conform the statements to actual results or changes in the Company's expectations.
SOURCE Neurologix, Inc.