Adeona Executes Agreement to Initiate Phase IIb Clinical Trial of Proprietary Zinc-Based Therapy in Lou Gehrig’s Disease (ALS)
ANN ARBOR, Mich., June 23, 2011 /PRNewswire/ — Adeona Pharmaceuticals, Inc. (NYSE Amex: AEN), a developer of innovative medicines for serious central nervous system diseases, announced today that it has expanded its pipeline of proprietary zinc-based therapies to include a planned Phase IIb clinical trial of patients suffering from amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease. Preparations are underway to evaluate the safety and efficacy of the Company’s proprietary drug candidates, AEN-100, a gastroretentive, sustained-release zinc-based tablet, and AEN-200, a copper tablet, in a multi-center, double-blind, placebo-controlled clinical trial in ALS patients intended to be conducted under an Investigational New Drug (IND) application. Adeona will provide the study medications and fund the clinical trial, which will be conducted by the neurology team at the PNA Center for Neurological Research in collaboration with The Institute for EthnoMedicine.
Planned Phase IIb Clinical Trial in ALS Patients Evaluating Adeona’s Zinc-Based Therapy
Preparation of the planned Phase IIb clinical protocol is currently ongoing for submission to the Food & Drug Administration (FDA) as an addition to a current IND application. Efforts are also underway for the manufacturing of clinical trial medications and protocol review by an Institutional Review Board. The multi-center trial is intended to take place at up to six major ALS centers in the United States. It is anticipated that the trial will enroll 60 ALS patients, who will continue on RILUTEKÃ‚® (riluzole) as the standard of care treatment. The patients will be randomized into treatment and matching placebo groups and will receive clinical trial medications for 12 months with periodic monitoring. The treatment group will receive Adeona’s proprietary drug candidates – AEN-100, a zinc-based tablet, and AEN-200, a copper tablet.
The planned co-primary endpoints are: 1) determining the safety of AEN-100 (elemental zinc) at 150 mg (two 75mg tablets) given to patients once daily with ALS by assessing adverse events and measuring zinc and copper levels every three months; and 2) determining the efficacy of AEN-100 by assessing the rate of disease progression as measured by the ALSFRS-R, a revised ALS functional rating scale that incorporates assessments of respiratory function.
The planned secondary endpoints are: 1) measuring levels of beta-methylamino-L-alanine (BMAA) in blood and urine to determine if there is a decline in these levels over the course of treatment; 2) following disease progression as measured by Forced Vital Capacity (FVC), a measurement of lung function that has been shown to correlate with disease survival; and 3) following progression of muscle weakness through quantitative strength measurements using hand-held dynamometry.
Ongoing Phase I/II Open Label Safety Study of Zinc Therapy in ALS Patients
Currently the clinical investigators at the PNA Center for Neurological Research are conducting a Phase I/II open label study of zinc therapy in ALS patients to determine the safety of zinc in conjunction with low doses of copper. To date, no safety issues related to zinc therapy have been observed in the ALS patients.
Potential Benefit of Zinc Therapy in ALS Patients
The clinical investigators at the PNA Center for Neurological Research cite multiple lines of scientific research that suggest a potential benefit of zinc therapy for ALS patients, including:
- During the 1950′s, an epidemic of ALS was discovered on the island of Guam and the Trust Territories of the Pacific that revealed a form of ALS that was 100 times more prevalent than in the rest of the world.
- Research on this cluster of ALS cases linked the neurological disease to the neurotoxin BMAA, a non-essential amino acid produced by cyanobacterium and found in large concentrations in food consumed by the people on Guam. Subsequent to the observations of a cluster of ALS cases on Guam, several groups have identified high concentrations of BMAA in the brain tissues of patients from North America and Europe with neurodegenerative diseases such as ALS.
- It has been demonstrated that BMAA binds strongly to transition metal ions such as zinc, copper, and nitrogen. If BMAA crosses into the brain and enters a compartment in which glutamate is bound to zinc, the glutamate/zinc complex separates and the BMAA binds with the zinc, leaving high levels of unbound glutamate. These elevated levels of unbound glutamate are believed to be highly neurotoxic in ALS patients. Zinc is thought to serve as an endogenous antioxidant in the central nervous system and helps protect the blood-brain barrier (BBB) against oxidative stress and may prevent the neurotoxin, BMAA, from crossing into the brain.
- The use of zinc therapy for ALS patients is further supported in animal models of ALS. Approximately 2% of ALS diagnoses are associated with a mutation in the superoxide dismutase (SOD1) gene. In ALS mutant SOD1 animal models, zinc supplementation has been shown to delay death.
- Genetic mutations affecting the ability of a protein known as copper/zinc superoxide dismutase (SOD1) to properly bind zinc are associated with the familial form of ALS, which shares many of the same features as the more prevalent sporadic form of ALS.
- Zinc is an important modifier of glutamate toxicity, a neurotransmitter linked to cell death in ALS patients.
“Our goal at the PNA Center for Neurological Research is to improve the quality of life of patients with neurological diseases, such as ALS. As observed in other central nervous system diseases, the biological availability of zinc is impaired in ALS patients. We hypothesize that by giving high doses of zinc to ALS patients, we can decrease the amount of toxicity from unbound glutamate and prevent neurotoxicity,” said Todd D. Levine, M.D., President of PNA Center for Neurological Research, Assistant Clinical Professor at the University of Arizona, Co-Director of the Banner Samaritan ALS Center in Phoenix, Arizona and Lead Principal Investigator of the planned clinical trial. “We are pleased to be working with Adeona and utilizing their proprietary zinc-based therapy that has already demonstrated clinical evidence of being very well tolerated by patients with superior bioavailability.”
“Adeona’s mission is to develop innovative medicines for serious central nervous system diseases. Expanding our pipeline to include ALS, a devastating and fatal neurological disease for which there is a shortfall of treatment options, is an ideal fit with our expertise and business model,” said James S. Kuo, M.D., M.B.A., Chief Executive Officer of Adeona. “Given the body of scientific evidence suggesting a therapeutic role for zinc in ALS, we look forward to the start of dosing ALS patients in this Phase IIb clinical trial to be conducted under an IND. We are pleased to be working with the dedicated neurologists at Phoenix Neurological Associates.”
About Amyotrophic Lateral Sclerosis (ALS)
ALS is a devastating progressive neurodegenerative disease that affects the nerve cells in the brain and the spinal cord in people of all ages and both sexes. It is estimated that as many as 30,000 Americans may have the disease at any given time. The progressive degeneration of the motor neurons in ALS eventually leads to the death of the patient. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. When motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. While non-invasive ventilation and gastrostomy tubes prolong life by 6-12 months, the average lifespan from time of symptom onset is 2-5 years. Currently, RILUTEK is the only FDA-approved drug for ALS. RILUTEK is an NMDA receptor antagonist and has been shown to prolong life in patients with ALS by 3 months. Presently, there is no cure for ALS, nor is there a known cause. For more information on ALS, please visit the ALS Association website at www.alsa.org.
About Phoenix Neurological Associates, Ltd.
Phoenix Neurological Associates, Ltd. (PNA) has been treating patients with neurologic diseases in Phoenix, Arizona for over 45 years. The PNA neurologists have a combined experience of over 90 years in treating all types of neurologic problems and are all board certified by the American Board of Psychiatry and Neurology. All of the PNA physicians also work at Banner Good Samaritan Medical Center where they serve as directors of the inpatient neurology service, Stroke Center, Neurodiagnostic Laboratory, ALS Clinic, and the Neuromuscular Clinic. For more information about PNA, please visit their website at www.phoenixneurology.com.
About PNA Center for Neurological Research
PNA Center for Neurological Research (Center) is an independent, not-for-profit organization based in Phoenix, Arizona. The Center was established by five of the neurologists from Phoenix Neurological Associates, Ltd., who are dedicated to discovering new treatments for patients with neurological diseases. The goal of the Center is to be a hub where philanthropists, advocates, organizations, family and friends of patients with a neurological illness could make donations that can support investigator-initiated clinical trials. The Center hopes to optimize proper treatments in order to improve outcomes for patients with neurological diseases. For more information on the Center, please visit its website at www.pnaresearch.org.
About AEN-100 and AEN-200
AEN-100 is Adeona’s proprietary, once-daily, gastroretentive, sustained-release oral tablet formulation of zinc acetate. AEN-200 is Adeona’s proprietary oral tablet formulation of copper sulfate.
About Adeona Pharmaceuticals, Inc.
Adeona is a pharmaceutical company developing innovative medicines for the treatment of serious central nervous system diseases. The Company’s primary strategy is to license product candidates that have demonstrated a certain level of clinical efficacy and develop them to a stage that results in a significant commercial collaboration. Currently, Adeona is preparing to make reaZin(TM), a prescription medical food for the dietary management of zinc deficiency associated with Alzheimer’s disease, commercially available. In addition, the Company is developing, or has partnered the development of, drug product candidates to treat multiple sclerosis, fibromyalgia, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and age-related macular degeneration. For more information, please visit Adeona’s website at www.adeonapharma.com.
RILUTEKÃ‚® (riluzole) is a registered trademark of sanofi-aventis U.S. LLC.
This release includes forward-looking statements on Adeona’s current expectations and projections about future events. In some cases forward-looking statements can be identified by terminology such as “may,” “could,” “potential,” “positions,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believe,” “estimates,” and similar expressions. These statements are based upon current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, many of which are difficult to predict and include statements regarding the planned Phase llb clinical trial, the ability to conduct the clinical trial under an IND application, the suggested role of zinc in the treatment of ALS, the planned primary and secondary endpoints and the anticipated number of clinical trial centers and enrolled patients. The forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from those reflected in Adeona’s forward-looking statements include, among others, our failure to obtain regulatory approval or market approval of the use of AEN-100 and AEN-200 in the treatment of ALS, failure to obtain approval to conduct the trial under the IND , failure of the clinical trial evaluating AEN-100 and AEN-200 to have favorable result such as a failure to show benefits of zinc therapy in ALS patients, a failure of the treatment group to have a decrease in toxicity from unbound glutamate or a failure of ALS patients treated with our proprietary zinc to successfully meet the planned primary and secondary endpoints, and other factors described in Adeona’s report on Form 10-K for the year ended December 31, 2010 and any other filings with the SEC. The information in this release is provided only as of the date of this release, and Adeona undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.
SOURCE Adeona Pharmaceuticals, Inc.