Alzheimer's Club

"ALAMEDA, Calif. (19 July 2005) - Avigen, Inc. (Nasdaq: AVGN - News), today announced encouraging results from the first patient treated in a Phase I/II clinical trial of AV201, the Company's drug candidate for the treatment of mid- to later-stage Parkinson's disease. The results from positron emission tomography (PET) brain scans obtained six months after AV201 infusion indicated an increased activity of the gene product, aromatic L-amino acid decarboxylase (AADC) in the targeted area of the brain, compared with the patient's pre-treatment PET scans. These findings are consistent with increased dopamine production and transgene expression.

In Parkinson's disease, brain dopamine concentrations decline, causing the main symptoms of muscle rigidity, slow movements, difficulty walking, and poor balance. Levodopa, the first-line drug for treating symptoms of the disease requires AADC in order to be converted to dopamine. However, over time AADC production in the brain also declines as Parkinson's disease progresses, making levodopa less effective. The mid- to later-stages of Parkinson's disease are often complicated by the toxic side effects associated with the higher doses of levodopa required to manage the disease's signs and symptoms. AV201 is designed to restore the activity of AADC in the brain, thereby extending the therapeutic usefulness and life of levodopa while avoiding side effects.

The Phase I/II clinical trial of AV201 in Parkinson's disease was initiated in December, 2004, at the University of California San Francisco (UCSF) and Lawrence Berkeley National Laboratory (LBNL). The study's Principal Investigator, Michael Aminoff, M.D., D.Sc., Director of the University of California-San Francisco Parkinson's Disease Clinic & Clinical Research Center, said, "This is an exciting beginning and a first for us: evidence of successful AADC gene transfer into humans. Most importantly for our patient, the procedure and gene appear to be safe. We're pleased with how well AV201 is being tolerated." Dr. Phillip Starr, neurosurgeon for the first patient in the study, added: "Based on the PET scans, it appears that the procedure and the use of convection-enhanced delivery to optimize the spread of AV201 worked as well as we could have hoped. We are enthusiastic about enrolling additional patients."

In another first, by using the dopamine tracer [18F] fluorometatyrosine (FMT)-based PET scanning rather than conventional fluorodopa PET, clinicians were able to visualize evidence of AADC gene expression with greater specificity. The use of FMT-PET technology was pioneered at LBNL by William Jagust, M.D., a neurologist and the Faculty Senior Scientist at LBNL and professor of Public Health and Neuroscience at UC Berkeley, and Jamie Eberling, staff scientist at LBNL and Associate Professor of Neurology at UC Davis. "The tracer is an excellent measure of gene expression," commented Eberling. "FMT-PET studies in animal models of Parkinson's disease have shown sustained AADC gene expression for more than 5 years after convection-enhanced gene delivery, along with sustained motor improvement," commented Dr. Jagust. "In this study, we are evaluating FMT-PET in individuals with Parkinson's disease as a surrogate marker of AADC activity and gene transfer. We are visualizing evidence of successful AADC gene transfer in the human brain for the first time. Both the apparent level and the duration of AADC expression are greater than any of us had anticipated, given the low dose of AV201 with which we began the study."

"These results did exceed our expectations, and we are encouraged that we are on the right track," said Dr. Dawn McGuire, a neurologist and Avigen's Chief Medical Officer. "It is, of course, too early to determine the therapeutic benefit or duration of gene expression. However, the value of this research cannot be underestimated, both for the individuals afflicted with Parkinson's disease and for understanding the potential of gene therapy in neurologic disease."

On April 5, 2005 Avigen announced that it will focus on the development of traditional pharmaceutical products, particularly small molecules and biologics. As part of the decision, the Company indicated it would divest its proprietary AAV technology but was committed to ensuring the continuation of the ongoing clinical programs, including the AV201 Program in Parkinson's disease.

Commenting on the impact of the trial and the strategic decision to reposition the Company, Kenneth G. Chahine, Ph.D., J.D., Avigen's President and CEO, said, "We chose this approach to treating Parkinson's disease not only for its therapeutic potential, but also the potential of visualizing AV201 activity using PET imaging. Therefore, we are very encouraged by these results which underscore the pioneering work of Avigen and its collaborators to provide novel therapeutics for neurological disorders."

Dr. Chahine continued, "This news reinforces the confidence we've always had in our AAV gene therapy program and its potential, but does not change our longer term strategic vision to seek external funding for the AAV technology. At this time, we are in advanced discussions with multiple parties who have the resources and commitment necessary to secure the long-term future and success of our AAV technology, including this very exciting Parkinson's trial. As we move through this process, foremost in our minds is to evaluate our options based on which one will deliver the best long-term value to our shareholders."

About Parkinson's Disease and AV201

Parkinson's disease (PD) is the second most common degenerative neurological disease after Alzheimer's disease, and is characterized by tremor, stiffness of the limbs and trunk, slowness of movement (bradykinesia), and poor balance. PD results from the death of specialized dopamine-producing cells in the brain. More than 2 million individuals in the United States and Europe are afflicted with Parkinson's disease. The primary and most effective treatment for this debilitating movement disorder is oral administration of levodopa, which is converted in the brain by the enzyme AADC, or dopa decarboxylase, into dopamine. As Parkinson's disease progresses, however, levodopa typically becomes less effective, believed due at least in part to the decline in concentrations of AADC resulting from continued neurodegeneration and cell death. Using higher levodopa doses in an attempt to compensate for less efficient conversion to dopamine often leads to intolerable side effects or toxicity. Avigen's AV201 is designed to restore the therapeutic effectiveness of levodopa by infusing the gene for AADC into the brain of patients, thus improving dopamine production. AV201 is an AAV vector containing the gene for human AADC which is delivered directly to the striatum, the part of the brain requiring dopamine to control movement. The patient and physician potentially can regulate the activity of AADC by raising or lowering the amount of levodopa taken. "This functional 'on-off' switch potentially enhances the safety of AV201 gene therapy," commented Dr. McGuire.

Early research conducted in animal models was performed by Krzysztof Bankiewicz, M.D., Ph.D., and Professor of Neurological Surgery at UCSF. Dr. Bankiewicz helped pioneer convection-enhanced delivery, and initiated its use to deliver AAV-AADC in animal models of Parkinson's disease. Studies have demonstrated AADC expression for more than 5 years after a single administration of AAV-AADC, along with continued therapeutic benefit in Parkinsonian nonhuman primates. These results encouraged Avigen to move "from bench to bedside" with the current Phase I-II clinical trial, designed to evaluate the safety of increasing doses of AV201 in individuals with mid-to-later-stage Parkinson's disease.

Participation in This Clinical Trial: Patients or physicians who are interested in learning more about this clinical study, please contact the UCSF Parkinson's Disease Clinic and Research Center Study Coordinator at 415-476-0947.

About Avigen: Avigen, Inc., based in the San Francisco Bay Area, is committed to providing physicians and their patients with innovative therapeutics for the treatment of neurological conditions. Avigen's strength lies in its innovative employees, rigorous science and a focused strategy on treatments for serious and life-threatening neurological disorders. Guided by a strong management team and supported by sound financials, Avigen's strategy is to build a robust pipeline through a combination of internal research, acquisitions and in-licensing with the goal of becoming a fully integrated pharmaceutical company. Additional information about Avigen can be found at http://www.avigen.com .

About Berkeley Lab: Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit the Lab website at http://www.lbl.gov .

Investors Please Note: This news release contains "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding Avigen's expectations for the clinical trial of AV201, the ability of AV201 to restore the activity of AADC in the brain, further successful AADC gene transfers into humans, anticipated enrollment of additional patients in the Phase I/II clinical trial and Avigen's intention to divest its proprietary AAV technology. These statements are not a guarantee of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from those projected in the forward-looking statements. These risks and uncertainties include whether the Phase I/II clinical trial results will validate and support the safety and efficacy of AV201, ability to enroll additional patients, uncertainties related to the timing and completion, if at all, of the divestiture of its proprietary AAV technology, uncertainty in obtaining or maintaining approvals and authorizations required by regulatory or institutional authorities, unanticipated responses to the treatment; and results from the first patient treated with AV201 are not necessarily indicative of results that will be obtained in the clinical trial. In addition, there are many other risks and uncertainties inherent in the development of drug products. Actual results may also differ from those projected in forward-looking statements due to risks and uncertainties associated with the conduct of clinical trials and in Avigen's operations and business. These risks and uncertainties are detailed in reports filed by Avigen with the Securities and Exchange Commission, including Avigen's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. Forward-looking statements contained in this new release are made as of this date and will not be updated."

Source: Avigen Announces Encouraging Early Data From Parkinson's Disease Clinical Trial. Biz.Yahoo.com (19 July 2005) [FullText]