NIH/NIDA Expert Warns Of Increasing Painkiller Abuse, Discusses NIDA Support For A New Drug Candidate For Opioid Withdrawal And Addiction

Main Category: Alcohol / Addiction / Illegal Drugs
Article Date: 10 Sep 2008 - 12:00 PDT

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Frank Vocci, Ph.D., Director of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse at the National Institute on Drug Abuse (NIDA), will make a public presentation today at 12:15 p.m. EDT at the St. Regis Hotel, Two East 55th Street, New York, New York to discuss the nation's growing prescription painkiller abuse problem and NIDA's support of a Columbia University/New York State Psychiatric Institute (NYSPI) exploratory clinical trial of a novel potential therapy for opioid withdrawal and addiction. The NIDA presentation will be part of Avigen, Inc.'s Research Day and will be webcast live and archived at http://www.avigen.com.

Use and Abuse of Opioid Medications

Opioid medications, including Vicodin, Darvoset, Codeine, Oxycontin, Demerol and Fentanyl, are commonly used to relieve acute and chronic pain and are one of the most widely prescribed classes of drugs in the United States:

- According to an August 31 article in the journal Pain, 4.3 million Americans take prescription painkillers regularly, and 10 million adults take them in any given week.

- According to NIDA, the prevalence of illicit opioid use, especially among adolescents, has increased at an alarming pace over recent years -- from 5.4 percent in 2002 to 6.4 percent in 2006.

- A 2004 NIDA study showed that 9.3 percent of 12th-graders reported using Vicodin and 5.0 percent reported using OxyContin without a prescription - making these medications among the most commonly abused prescription drugs by adolescents.

- According to the NeuroTechnology Industry 2008 report published by NeuroInsights, the economic burden of drug addiction in the United States is more than $366 billion.

"This is truly an unmet medical need in this country. The non-medical use or abuse of prescription drugs - primarily opioids - is a serious and growing public health problem. In fact, an estimated 33 million people have used prescription drugs for non-medical reasons in their lifetimes - approximately 15 percent of the U.S. adult population," said Dr. Vocci.

Opioid Withdrawal

The use of opioid drugs can cause the development of analgesic tolerance and physical dependence, which leads to withdrawal symptoms when opioid therapy is discontinued. Symptoms of withdrawal may begin as early as a few hours after usage is substantially lowered. Symptoms include a craving for the drug, restlessness, moodiness, insomnia, yawning, abdominal cramps, diarrhea, nausea and vomiting, and muscle aches. There are no approved drugs to treat withdrawal, and treatments employed often have undesirable side effects and may not provide enough relief from the intense physical and mental withdrawal symptoms, leading patients in detox to quit before completing their program.

To that end, NIDA will be the largest funder of a Columbia/NYSPI safety and tolerability clinical trial of AV411, a non-opioid compound being developed by Avigen, Inc., that may reduce the symptoms of opioid withdrawal and decrease addiction, and may improve the pain relief of opioids.

How AV411 May Work in Opioid Withdrawal

AV411 does not directly work on the brain's neurons, like some therapies, but acts on glial cells, which outnumber neurons by nearly 10 to 1. Current pharmaceutical strategies involve the administration of compounds that bind to the same neuronal receptors as the opioids, as well as opioid antagonists that block the action of opioids throughout the brain and nervous system. AV411's unique mechanism of action involves attenuation of glial cell activation. Recent research has shown that opioids not only affect neurons but also activate glial cells. This glial cell activation and concomitant pro-inflammatory cytokine release has been proposed to contribute to conditions of opioid tolerance, dependence and withdrawal.

"In preclinical studies, opioid treatment induces brain glial cell activation that correlates with both opioid tolerance and dependence," explained the study's principle investigator, Sandra D. Comer, Ph.D., Associate Professor of Clinical Neurobiology at NYSPI and Columbia University. "Preclinical studies have shown that AV411 can attenuate the behavioral signs of opioid withdrawal and corresponding glial cell activation without conferring adverse side effects. My research team and our partners are eager to confirm these findings in humans and help move this potentially important new medicine through clinical development."

"NIDA has chosen to fund this study based on its review of Avigen's research and its interest in the role of glial-attenuation as a novel way to treat opioid withdrawal symptoms, a common result of opioid abuse that can hinder recovery," Dr. Vocci said.

About the Trial

In the new trial, to be operated jointly by the New York State Psychiatric Institute (NYSPI) and Columbia University, AV411 will be administered twice daily to heroin addicts who are maintained on morphine, an opiate analgesic drug commonly used to treat patients with heroine withdrawal symptoms, over a 14-day period. The trial will assess preliminary efficacy of AV411 for reducing symptoms of opioid withdrawal and its impact upon opioid-induced analgesia.

About AV411

AV411 is a first-in-class orally bioavailable small molecule glial attenuator. It can suppress pro-inflammatory cytokines IL-1 beta, TNF alpha, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. While considered a New Molecular Entity (NME) in the United States and Europe, the drug was first approved in Japan over 15 years ago. The drug has been prescribed to over one million patients for a different indication and has a good post-marketing safety profile in nearly 15,000 patients studied at the prescribed doses.

As part of its program investigating glial attenuation as a novel approach to the treatment of neuropathic pain, preclinical research has revealed that AV411 can attenuate opiate-induced glial activation and both behavioral and neurochemical markers of opioid-induced reward and withdrawal. More recent NIDA-sponsored preclinical studies indicate potential utility in methampthetamine relapse which may also be linked to glial regulation. Based on its research, Avigen has filed for patents protecting this use of AV411, as well as for patents on AV411 analogs which the company believes have the potential to be effective second generation molecules.

What are Opioids?

For more information on what opioids are, and opioid-induced constipation (OIC), please see:
All About Opioids and Opioid-Induced Constipation (OIC)

About Avigen

Avigen is a biopharmaceutical company focused on developing and commercializing unique small molecule therapeutics to treat serious neurological disorders, including neuropathic pain and neuromuscular spasm and spasticity. Avigen's strategy is to complete the requirements of clinical development for each of the candidates in its product pipeline, and continue to look for opportunities to expand its pipeline through a combination of internal research, acquisitions, and in-licensing, with the goal of becoming a fully integrated commercial biopharmaceutical company that remains committed to its neurology products. Avigen is currently developing AV650 for spasticity and neuromuscular spasm and AV411 for neuropathic pain. Additionally, the company is advancing toward clinical trials AV513, a novel therapy for the treatment of multiple bleeding disorders, including hemophilia A and B. For more information about Avigen, consult the company's website at http://www.avigen.com.

About NIDA

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and further information on NIDA research can be found on the NIDA web site at http://www.drugabuse.gov.

Statement under the Private Securities Litigation Reform Act

This press release contains forward-looking statements, which include statements relating to Avigen's belief that AV411 may be a therapy for reducing the symptoms of opioid withdrawal and improving the efficacy of opioids, ultimately decreasing abuse liability, and its intention of using this trial to build upon AV411's glial-attenuating properties; using AV411 analogs as second generation molecules; completing the requirements of clinical development for each of the candidates in its product pipeline; continuing to look for opportunities to expand its pipeline; and becoming a fully integrated commercial biopharmaceutical company. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include those detailed in reports filed by Avigen with the Securities and Exchange Commission, including Avigen's quarterly report on Form 10-Q for the period ended June 30, 2008, under the caption "Risks Related to Our Business" in Item 2 of Part I of that report, which was filed with the Securities and Exchange Commission on August 11, 2008.

Avigen