Avigen Announces AV650 Did Not Meet Efficacy Endpoints in Phase 2b Clinical Trial for Spasticity in Patients With Multiple Sclerosis

ALAMEDA, Calif., Oct 21, 2008 (GlobeNewswire via COMTEX News Network) -- Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company innovating therapeutics for neurological care, today announced that the top-line data from its Phase 2b study of AV650 (tolperisone HCl) for the treatment of spasticity associated with multiple sclerosis (MS) did not achieve statistical significance on its primary endpoint of a reduction from baseline of patients' Ashworth scores as compared to placebo. The reduction of muscle spasm, a secondary endpoint, also failed to achieve statistical significance. There were no safety issues. The trial was adequately powered, and all statistical parameters were in line with expectations.

"We are disappointed with the result of this trial," said Kenneth Chahine, Ph.D., J.D., Avigen's President and Chief Executive Officer. "We had hoped AV650 would become an important new treatment option for people in the United States who currently suffer from spasticity. While we will continue to review the additional data from the trial and consider further options, we are confident in the trial design and the quality of the top-line results.

"We will now shift our focus and resources toward the clinical development of our AV411 program. At the end of 2008, we will have approximately $50 million of cash and securities. This represents approximately 2 years of cash and provides a strong foundation for advancing the development of AV411 for neuropathic pain and opioid addiction and withdrawal."

About the Trial

This double-blind, randomized clinical trial was conducted in 27 MS centers in Germany and other European countries to evaluate safety, tolerability, pharmacokinetics and efficacy in up to 150 MS patients suffering from spasticity. This trial was being conducted to Good Clinical Practice standards by a leading international clinical research organization. Following a five-week double blind assessment, patients were offered the opportunity to continue for up to twelve months in an open-label safety phase. The primary efficacy endpoint was the Ashworth scale, a standard tool used in the clinic to measure increased resistance to passive limb movement. Secondary endpoints included Brief Pain Index (BPI), painful spasm diaries, and clinical impression of change.

Avigen is a biopharmaceutical company focused on developing and commercializing small molecule therapeutics to treat serious neurological disorders, including neuropathic pain and opioid addiction and withdrawal. 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 AV411 for neuropathic pain, as well as opioid withdrawal and addiction in collaboration with the National Institute on Drug Abuse. Additionally, the company is advancing AV513, a novel therapy for the treatment of multiple bleeding disorders, including hemophilia A and B, toward clinical trials. For more information about Avigen, consult the company's website at www.avigen.com.

The Avigen, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=2981

Statement under the Private Securities Litigation Reform Act

The statements in this press release relating to Avigen's expectations regarding the quality of the top-line results from the AV650 Phase 2b spasticity trial and its consideration of further options based on a review of additional data from the trial, its expectation regarding the level of its financial resources at December 31, 2008 and how long its financial resources will last, its expectation regarding shifting resources toward the clinical development of AV411, and its goal of becoming a fully integrated commercial biopharmaceutical company remaining committed to its neurology products, are forward-looking statements. These risks and uncertainties include, among others, the fact that development of small molecule therapeutics and other therapeutic discovery and development is a time- and resource-intensive process, which may result in the expenditure of a significant amount of time and resources with no progress towards clinical trials or marketable product resulting from the effort; the risk that Avigen will not be able to obtain regulatory approvals for its drug products, which is required prior to marketing drug products; and the risk that early positive preclinical and clinical results will not guarantee that the potential products will ultimately be effective in treating the indications for which they are developed, or exhibit the unique properties they appear to possess. In addition, there are many other risks and uncertainties inherent in the development of drug products. Other risks and uncertainties relating to Avigen are 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 SEC on August 11, 2008.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Avigen, Inc.

Avigen, Inc.
Michael Coffee, Chief Business Officer
510-748-7372
IR@avigen.com

Avigen Completes Multi-Center AV650 Phase 2b Spasticity Trial in Patients With Multiple Sclerosis

Top Line Data Expected in Q4 2008

ALAMEDA, Calif., Sep 18, 2008 (GlobeNewswire via COMTEX News Network) -- Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company innovating therapeutics for neurological care, today announced the completion of the double-blind portion of its Phase 2b trial for AV650 (tolperisone HCl) in the treatment of spasticity associated with multiple sclerosis (MS). This Phase 2b spasticity trial is evaluating the safety, tolerability and efficacy of AV650 in MS patients at doses up to 900mg/day for one month followed by an open-label safety extension. The trial is being conducted in top MS centers in Germany and several other European countries.

"The completion of this trial in less than a year marks a significant milestone for the AV650 program and Avigen," said Kenneth Chahine, Ph.D., J.D., Avigen's President and Chief Executive Officer. "The rapid enrollment further supports the need for new and non-sedating agents to treat spasticity, and we have confidence that our planned Phase 3 trials can be completed in a similar timeframe. While the blinded portion of the trial is complete and will report before the end of 2008, more than 90% of the patients have elected to participate in the on-going open-label extension and will continue to receive AV650 for up to an additional twelve months."

Avigen is developing AV650 for commercialization in the North American market for the treatment of disabling neuromuscular spasticity and spasm under a license and supply agreement with Sanochemia Pharmazeutika AG, Vienna, Austria. AV650 is considered a New Chemical Entity (NCE) in the United States.

Tolperisone is an orally administered, centrally acting small molecule marketed for the treatment of neuromuscular spasticity and spasm in Europe and Asia. Avigen's U.S. development program is designed to build on the extensive ex-U.S. safety and efficacy experience with this compound. Versions of tolperisone have been approved for marketing in Germany for over 10 years. Sanochemia and its European marketing partner, Orion Pharma, currently market a proprietary 150mg tablet formulation of tolperisone in Germany under the brand name Viveo(r).

Spasticity is considered one of the main symptoms of the more than 2.5 million people with MS worldwide, affecting up to 60% of this population. Randall Schapiro, M.D, Director of The Schapiro Center for Multiple Sclerosis at the Minneapolis Clinic of Neurology and Clinical Professor of Neurology at the University of Minnesota, commented, "MS patients must cope with significant side effects from currently available treatments for spasticity, including drowsiness, fatigue and cognitive impairment. These side effects do affect their quality of life. We recognize the need for better-tolerated, non-sedating therapies in the United States, and we are encouraged by the European experience of tolperisone."

About the Trial

This double-blind, randomized clinical trial is being conducted in 27 MS centers in Germany and other European countries. It will evaluate safety, tolerability, pharmacokinetics and efficacy in up to 150 MS patients suffering from spasticity. This trial is being conducted to Good Clinical Practice standards by a leading international contract research organization. Following a four-week double blind assessment, patients are offered the opportunity to continue for up to twelve months in an open-label safety phase. The primary efficacy endpoint is the Ashworth scale, a standard tool used in the clinic to measure increased movement. Secondary endpoints include Brief Pain Index (BPI), painful spasm diaries, and clinical impression of change.

About Neuromuscular Spasm and Spasticity

Chronic or recurrent muscle spasm is a sudden, violent, painful contraction of muscles typically associated with serious neurological disorders such as Lou Gehrig's disease (ALS), multiple sclerosis, stroke, spinal cord injury, and cerebral palsy. These painful muscle spasms are often, but not always, associated with spasticity, an abnormality in muscle "tone." Spastic limbs become stiff and rigid because the muscles fail to relax, lacking normal regulation by the damaged nervous system. Both spasticity and sudden, painful muscle spasms can occur as complications of the neurological disorders mentioned above. Spasticity is a common symptom in multiple sclerosis, which affects 2.5 million worldwide.

About Avigen

Avigen is a biopharmaceutical company focused on developing and commercializing 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, as well as opioid withdrawal and addiction in collaboration with the National Institute of Drug Abuse. Additionally, the company is advancing AV513, a novel therapy for the treatment of multiple bleeding disorders, including hemophilia A and B, toward clinical trials. For more information about Avigen, consult the company's website at www.avigen.com.
Statement under the Private Securities Litigation Reform Act

The statements in this press release relating to Avigen's expectations regarding the timely and reliable completion of its clinical trials, its expectations regarding reporting AV650 Phase 2 top-line data in the fourth quarter of 2008, its expectations regarding initiating and completing planned Phase 3 clinical trials in a similar timeframe to the Phase 2b spasticity trial in patients with MS, and its goal of becoming a fully integrated commercial biopharmaceutical company remaining committed to its neurology products are forward-looking statements. 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, among others, the fact that development of small molecule therapeutics and other therapeutic discovery and development is a time- and resource-intensive process, which may result in the expenditure of a significant amount of time and resources with no progress towards clinical trials or marketable product resulting from the effort; the risk that Avigen will not be able to obtain regulatory approvals for its drug products, which is required prior to marketing drug products; and the risk that early positive preclinical and clinical results will not guarantee that the potential products will ultimately be effective in treating the indications for which they are developed, or exhibit the unique properties they appear to possess. In addition, there are many other risks and uncertainties inherent in the development of drug products. Other risks and uncertainties relating to Avigen are 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 SEC on August 11, 2008.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Avigen, Inc.

Avigen, Inc.
Michael Coffee, Chief Business Officer
510-748-7372
Fax: 510-748-7155
1301 Harbor Bay Parkway
Alameda, CA 94502

IMPAX Reports Positive Results in Phase III Trial with IPX056

-Provides Update on Brand Pharmaceutical Program-

-Company Presenting Today at the Bank of America Specialty Pharmaceutical Conference-

HAYWARD, Calif.--(BUSINESS WIRE)--IMPAX Laboratories, Inc. today announced that IPX056, an investigational extended-release formulation of baclofen, has met its clinical endpoints in a Phase III study of spasticity in multiple sclerosis patients. The Company also is providing an update on its brand pharmaceutical product program, which resides in its IMPAX Pharmaceuticals Division.

In a 173-patient, placebo and active comparator-controlled double blind Phase III study with a seven-week open label follow on, IPX056 was shown to be effective versus placebo in reducing spasticity in multiple sclerosis patients. IPX056 is an extended-release formulation of baclofen, the drug of choice in the treatment of spasticity, which has the potential to offer improved control of symptoms and dosing convenience.

“We are very excited with the results of this study, and are planning to meet with the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year to discuss the results of this study and determine the next steps in the submission of a new drug application (NDA) for IPX056,” said Larry Hsu, Ph.D., president and chief executive officer of IMPAX Laboratories. “Such spasticity treatments represent a $1.6 billion market in the U.S. and IPX056 may fill an unmet medical need in these patients.”

The IMPAX Pharmaceuticals division of IMPAX Laboratories currently has two products in its development pipeline, directed to neurology as a therapeutic focus, with four other central nervous system (CNS) specific products undergoing feasibility assessment. The Company filed an Investigational New Drug application for IPX066, a controlled-release formulation of Carbidopa/Levodopa in July 2008, and expects to initiate studies in Parkinson’s disease patients by the end of this year and is targeting an NDA submission in mid-2011.

Michael Nestor, divisional president of IMPAX Pharmaceuticals said, “We are very pleased with the progress we have made in advancing our proprietary, brand products and expect to continue this progress with an expansion in our R&D staff this year. The CNS space is ideally suited to our core competency in drug delivery, as so many products are candidates for improved dosing and administration and the market is large and growing at almost 10% annually, faster than the total U.S. pharmaceutical market. In addition, the neurology market is readily addressable by a small and focused sales force, given the concentration of physicians writing prescriptions. We currently have 66 specialty sales representatives to market our products, and to serve as a contract force for others,” Mr. Nestor added.

As previously announced on July 31, 2008, Arthur A. Koch, Jr., senior vice president and chief financial officer of IMPAX Laboratories, will present at the Bank of America 2008 Specialty Pharmaceuticals Conference today at 9:30 a.m. Eastern time. The conference will be held at the Southampton Inn, Long Island, New York.

Individuals may listen to the live or an archived presentation made at the conference, which will be posted in the investor relations section of the Company’s web site at www.impaxlabs.com. To listen to the live presentation, please go to the web site 15 minutes prior to its start to register, download, and install the necessary audio software. This presentation will be archived on the Company’s web site for 90 days. The Company’s regular Corporate presentation will be updated and posted on the Company’s web site today as well.

About IMPAX Laboratories, Inc.

IMPAX Laboratories, Inc. is a technology based specialty pharmaceutical company applying its formulation expertise and drug delivery technology to the development of controlled-release and specialty generics in addition to the development of brand products. IMPAX markets its generic products through its Global Pharmaceuticals division and will market its brand products through the IMPAX Pharmaceuticals division. Additionally, where strategically appropriate, IMPAX has developed marketing partnerships to fully leverage its technology platform. IMPAX Laboratories is headquartered in Hayward, California, and has a full range of capabilities in its Hayward and Philadelphia facilities. For more information, please visit the Company's Web site at: www.impaxlabs.com.

IMPAX Laboratories, Inc.
Larry Hsu, Ph.D. President & CEO
510-476-2000, Ext. 1111
or
Arthur A. Koch, Jr., Sr. VP & CFO
215-933-0351
or
Mark Donohue, Sr. Director IR
215-933-3526
www.impaxlabs.com
or
Investor Relations Contacts:
Lippert/Heilshorn & Associates, Inc.
Kim Sutton Golodetz
kgolodetz@lhai.com
212-838-3777
or
Bruce Voss
bvoss@lhai.com
310-691-7100
www.lhai.com

Expert Opinion Paper - National MS Society Makes Recommendations Regarding Therapeutic Use Of Cannabis

Washington, DC: Cannabis has the potential to treat symptoms of multiple sclerosis as well as limit the progression of the disease, according to an expert opinion paper published by the US National Multiple Sclerosis Society. However, the Society stopped short of recommending that MS patients use the drug medicinally.

“Although it is clear that cannabinoids have potential both for the management of MS symptoms such as pain and spasticity, as well as for neuroprotection, the Society cannot at this time recommend that medical marijuana be made widely available to people with MS for symptom management,” the Society concludes. “This situation might change, should better data become available that clearly demonstrate benefit.”

The Society recommends that future clinical trials focus on methods of cannabinoid administration that deliver the drug to the bloodstream rapidly, such as vaporization.

The Society also recommends clinical trials be performed to investigate and quantify cannabis’ potential to slow disease progression, citing “anecdotal reports from patients … that cannabis reduces the frequency of their MS attacks.”

Investigators at Plymouth’s Peninsula Medical School in Britain recently announced that they had recruited nearly 500 MS patients for a three-year clinical trial assessing whether the use of oral THC can significantly slow the onset of multiple sclerosis.

Clinical data reported in 2006 from an extended open-label study of 167 multiple sclerosis patients found that the use of whole plant cannabinoid extracts relieved symptoms of pain, spasticity, and bladder incontinence for an extended period of treatment (mean duration of study participants was 434 days) without requiring subjects to increase their dose.

Results from a separate two-year open label extension trial in 2007 also reported that the administration of cannabis extracts was associated with long-term reductions in neuropathic pain in select MS patients. On average, patients in the study required fewer daily doses of the drug and reported lower median pain scores the longer they took it.

Commenting on the MS Society report, NORML Deputy Director Paul Armentano said: “The MS Society’s recommendations are a positive step, but they don’t go far enough. Surveys indicate that as many as one out of two MS patients use cannabis therapeutically, yet this report does nothing to challenge these patients legal status as criminals.”



For more information, please contact Paul Armentano, NORML Deputy Director, at: paul@norml.orgThis e-mail address is being protected from spam bots, you need JavaScript enabled to view it

Full text of the MS Society paper, “Recommendations Regarding the Use of Cannabis in Multiple Sclerosis”. Additional information on cannabinoids and multiple sclerosis is available from NORML. The paper can also be downloaded from the NMSS web site in PDF format by clicking on the title of this posting.

http://norml.org/

GW Pharma plunges as cannabis drug trial disappoints

Phase III MS Neuropathic Pain Trial Preliminary Results


- Very high patient response rate to Sativex but statistical significance narrowly missed due to large, unexpected placebo response -
- Ongoing Phase III trial in MS Spasticity on track and due to report in Q4 -
- MS Spasticity trial has specific features designed to address placebo response -

Porton Down, UK, 8 April 2008: GW Pharmaceuticals plc (AIM: GWP) announces preliminary results of a Phase III double-blind randomised placebo-controlled study of Sativex® in 339 patients with central neuropathic pain due to Multiple Sclerosis (MS), who have achieved inadequate pain relief with existing therapies.

This study is one of three Phase III trials for Sativex underway in 2008, each of which targets a distinct indication. The other European Phase III study in MS Spasticity, requested last year by the UK regulator in order to gain approval in this indication and which involves a different trial design, is on track to report later this year.

The primary efficacy endpoint in the study reported today was the proportion of patients whose pain reduced by at least 30% as measured on a 0-10 numerical rating scale (“responder analysis”). In this study, 50% of Sativex patients experienced a pain reduction of at least 30%, the second largest response rate seen in any Sativex study and amongst the largest seen for any pain treatment in the published literature. However, although the difference between the Sativex and placebo groups was clearly in favour of Sativex, it narrowly failed to reach statistical significance in this trial due to an unexpectedly large placebo response. Key secondary endpoints followed the same trend – in favour of Sativex versus placebo but not at a statistically significant level due to the very high placebo response.

The placebo response in the study reported today appears related to dosing design, whereby patients were able to self-administer the oral spray at will. This was intended to reflect as far as possible the “real world” use of Sativex whereby patients initially experiment with dosing of Sativex to find their optimum dose level and which, once established, is usually maintained thereafter. Analysis of the efficacy data at fixed dose levels demonstrates a highly significant difference between Sativex and placebo. However, a consequence of allowing patients to determine their own dose was that patients on placebo took significantly more doses than patients on Sativex, thus confounding the overall comparison. This validates the decision by GW last year to adopt a fixed target dose approach in both the ongoing studies of Sativex in MS Spasticity and Cancer Pain.

The safety profile of Sativex in this study is superior to that seen in previous studies. The withdrawal rate due to adverse events was 9% on Sativex vs 6% on placebo, the lowest seen in long duration Sativex studies. As in previous studies, the most common adverse event was dizziness. The rate of this adverse event was less than in previous studies (20% on Sativex vs 8% on placebo as compared with 32% vs 9%).

GW’s regulatory strategy is to file Sativex for approval in MS Spasticity in Europe and Cancer Pain in the United States. In Europe, regulatory discussions with the Medicines and Healthcare products Regulatory Agency (MHRA) have exclusively focused on MS Spasticity, a distinct indication supported by different clinical trials. Last year, the MHRA provided clear guidance on the additional clinical trial required for approval. As indicated above, this trial is on track and due to report later this year.

Dr Stephen Wright, R&D Director, said: “It is clear from the size of the response seen in this study that Sativex provides important improvements for these high need patients, even those that have failed to respond to all other pain treatments. It is frustrating that the extent of the placebo response has narrowly prevented the benefits seen on Sativex translating into a statistically significant outcome. The design of the MS Spasticity study due to report later this year is specifically focused on limiting the potential for placebo response and we expect the outcome of this trial and our other studies to confirm the benefits of Sativex.”

“MS Spasticity is a distinct indication supported by different clinical trials and the route to regulatory approval for Sativex as a treatment for this indication remains clear and unaffected by the data announced today.”

Dr Stuart Ratcliffe, Principal Investigator of the study and most recently Director, Pain Research Group, St Bartholomew’s and The Royal London Hospitals NHS Trust, added: “In seeking to replicate the real world usage of Sativex, where each patient finds his or her own optimum dose level, the design of this trial appears to have encouraged an abnormally high placebo response. However, this in no way should detract from the beneficial effects of Sativex seen in the study. Patients saw a marked improvement in their symptoms, a highly impressive effect since they are treatment resistant, and the study recorded the lowest drop-out rate, demonstrating the mild side effect profile of Sativex. My experience with Sativex continues to show that it is an extremely helpful medicine for these high need patients and I am confident that the ongoing trials which seek to address the placebo issue will demonstrate its value.”

Following a comprehensive review of this data, GW intends to carry out a further study in this patient population.

As at 31 March 2008, GW’s cash position stood at £18.5m.

There will be a conference call for analysts today at 8.30am BST. Analysts should contact Gemma Cross Brown at Financial Dynamics on +44 (0) 20 7831 3113 for details. There will be a live audio web cast of this call, which will be accessible on the press releases page in the investor relations section of the GW website (www.gwpharm.com). A recording of this call will be available on the GW website later today.

Enquiries:

GW Pharmaceuticals plc
(Today) + 44 20 7831 3113

Dr Geoffrey Guy, Executive Chairman

(Thereafter) + 44 1980 557000

Justin Gover, Managing Director


Financial Dynamics

+ 44 20 7831 3113

David Yates / Ben Atwell

Notes to Editors

About GW
GW was founded in 1998 and listed on the AiM, a market of the London Stock Exchange, in June 2001. Operating under license from the UK Home Office, the company researches and develops cannabinoid pharmaceutical products for patients who suffer from a range of serious ailments, in particular pain and other neurological symptoms. GW has assembled a team of over 100 scientists with extensive experience in developing both plant-based prescription pharmaceutical products and medicines containing controlled substances. GW occupies a world leading position in cannabinoids and has developed an extensive international network of the most prominent scientists in the field.

Sativex Phase III trial in MS Neuropathic Pain

This study focused on high need MS patients, who were already taking a range of currently available pain treatments, and yet still suffered severe pain, and who remained on such treatments during the course of the study. Improvements seen in this study therefore represent benefits over and above that which can be achieved with currently available medication. The study recruited patients in the UK, Canada, France, Spain and the Czech Republic and the duration of treatment in the study was 14 weeks.

GW has previously carried out a similar Phase III study with positive results, which was published in the peer-reviewed journal, Neurology. That study showed that Sativex was significantly superior to placebo in reducing pain (p=0.005) and sleep disturbance (p=0.003)1. In this previous study the placebo response was less than that seen in the study reported today.

Clinical & Regulatory Strategy for Sativex

The strategy for Sativex is focused on four specific therapeutic indications, each of which represents a distinct regulatory opportunity and each of which requires a distinct set of clinical efficacy data. These indications are as follows:

Each of these target indications is supported by existing positive Phase III data and will continue to be supplemented by further late stage trials over the next few years in order to supplement globally approvable regulatory packages and provide more data to support the marketing of the product post approval.

The lead indication for Sativex differs across different regions of the world. In the US, Cancer Pain is the chosen initial target. In Canada, MS Neuropathic Pain was the first approved indication, which has now been successfully followed by the approval in Cancer Pain. In Europe, the entry point for Sativex is MS, with MS Spasticity representing the nearest term approval possibility.

This clinical and regulatory programme is designed to provide multiple opportunities over the next few years to obtain approvals for Sativex across various indications in a number of territories.

1. D.J.Rog, T.J.Nurmikko, T.Friede, and C.A Young. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005;65:812

NovaDel Announces Positive Data from Pilot Pharmacokinetic Study Comparing Tizanidine Oral Spray to Zanaflex(R) Tablets

FLEMINGTON, N.J., Apr 07, 2008 (BUSINESS WIRE) --

NovaDel Pharma Inc. (AMEX: NVD), a specialty pharmaceutical company developing oral spray formulations for a broad range of marketed treatments, today announced pharmacokinetic (PK), pharmacodynamic (PD) and safety results from its Pilot PK Study of its Oral Spray formulation of tizanidine compared to tizanidine tablets marketed as Zanaflex(R). Tizanidine is a leading drug indicated for the management of spasticity. Spasticity is a condition manifested in various neurological disorders, such as multiple sclerosis, stroke, cerebral palsy and spinal cord injury. This study demonstrates drug delivery across the oral mucosa, achieving faster entry of drug into the bloodstream with greater bioavailability and importantly in this particular disorder, avoiding the need to swallow a tablet or capsule.

Objectives of the Study
This Pilot Pharmacokinetic Study was designed to compare the PK profile of 2 mg, 4 mg and 8 mg Oral Spray (OS) doses of tizanidine hydrochloride to a 4 mg Zanaflex(R) (tizanidine hydrochloride) tablet dose in healthy male volunteers under fasting conditions. Assessment of the PD properties of tizanidine OS was made by administering the Digit Symbol Substitution Test (DSST) and measuring drowsiness levels via a self-assessment scale and changes in blood pressure and pulse rate associated with study drug administration. Safety and tolerability information was also collected.

Results of the Study
The data show substantially greater exposure to tizanidine from the OS formulations and earlier detectable plasma drug levels for OS doses versus the tablet (approximately 10 minutes and 17 minutes respectively, where p values ranged from 0.0002 to 0.0117). When dose normalized (to 4 mg), the bioavailability of the tizanidine OS doses were 2.04 to 3.49-fold greater than that of the 4 mg tablet.

The 2 mg oral spray and 4 mg tablet doses gave comparable results in the DSST test where positive scores were observed compared to baseline. There was an apparent decrease in the DSST scores after administration of the 4 mg and 8 mg OS study drugs. A decrease in the DSST score indicates a decrease in attention, perceptual speed, motor speed, visual processing and memory. Self-assessment of drowsiness indicated that subjects dosed with either the 4 mg or 8 mg OS assessed themselves as being "a bit more" or "much more" sleepy/drowsy than they were at baseline at a frequency comparable to that reported for the tablet. Reductions in blood pressure and pulse rate, recognized side effects of tizanidine, were observed with all doses of tizanidine OS and the tablet.

A total of 3 subjects had Adverse Events (AEs) of mild or moderate bradycardia and hypotension, which are well-recognized side effects of tizanidine, after the highest dose of tizanidine OS (8 mg). No subjects prematurely discontinued from the study due to AEs, and there were no Serious Adverse Events (SAEs) or deaths. No subjects reported any symptoms in the oral cavity. These results indicate that tizanidine OS is a well tolerated and safe based on the relatively small number of reported AEs and the absence of any SAEs both locally and systemically.

"These results further demonstrate the potential of our technology to rapidly deliver a variety of drugs across the oral mucosa" commented Mr. Steven Ratoff, NovaDel's Chairman of the Board and Interim President & Chief Executive Officer. "These results indicate that substantially greater bioavailability can be achieved with tizanidine in an oral spray form which may offer the opportunity for a product with an improved safety and side effect profile compared to tablets."

ABOUT THE STUDY
This was a single-center, 4-way crossover, open-label, dose-ranging, multiple-treatment PK study in healthy male volunteers 18 to 40 years old. There were 14 subjects planned; 14 subjects enrolled. Data from 14 subjects were evaluable for PK, pharmacodynamic and safety analyses. Treatments were separated by a period of 7 (+/- days). Blood samples (5.5 ml/sample) for PK evaluation were collected at each visit.

The OS test article used in this study has greater than 12 months physical and chemical stability and was supplied in 2 mg, 4 mg and 8 mg strengths. The tizanidine tablet was supplied from commercial sources as Zanaflex(R) from Acorda Therapeutics, Inc.

Measurements:
Pharmacokinetic: Maximum drug concentration (C(max)); time to maximum drug concentration (T(max)), time to detectable drug concentration (T(det)); elimination rate constant (K(e)); bioavailability (relative to the oral tablet); elimination half-life (t(1/2)); absorption t(1/2); area under the concentration time curve (AUC), including AUC(0-T), calculated from time 0 to the last non-zero concentration (C(T)), AUC(0-Infinity), calculated by extrapolation of AUC(0-T) to infinity by adding C(T)/K(e) to AUC(0-T); clearance (CL/F), clearance corrected for body weight (CL/F/kg); volume of distribution (Vd/F) and volume of distribution corrected for body weight (V(d)/F).

Pharmacodynamic: Digit Symbol Substitution Test (DSST), self-assessment of drowsiness, blood pressure (BP), and pulse rate.
Safety: Changes in physical examinations, including oral soft tissue examinations at after each lingual spray dosing, laboratory parameters, adverse events (AEs), and vital signs.

ABOUT SPASTICITY
Spasticity affects over 500,000 people in the U.S. alone. Spasticity is not a disease, but rather a symptom of various neurological disorders, including, but not limited to multiple sclerosis (MS), spinal cord injury, stroke and cerebral palsy. These disorders cause a change in the balance of signals between the central nervous system and the muscles. This imbalance leads to involuntary tensing, stiffening and contracting of muscles. Tizanidine is the most widely prescribed treatment for spasticity with approximately 4 million prescriptions written annually.

ABOUT NOVADEL PHARMA
NovaDel Pharma Inc. is a specialty pharmaceutical company developing oral spray formulations for a broad range of marketed drugs. The Company's proprietary technology offers, in comparison to conventional oral dosage forms, the potential for faster absorption of drugs into the bloodstream leading to quicker onset of therapeutic effects and possibly reduced first pass liver metabolism, which may result in lower doses. Oral sprays eliminate the requirement for water or the need to swallow, potentially improving patient convenience and adherence.

NovaDel's oral spray technology is focused on addressing unmet medical needs for a broad array of existing and future pharmaceutical products. The Company's most advanced oral spray candidates target angina, nausea, insomnia, migraine headaches and disorders of the central nervous system. NovaDel plans to develop these and other products independently and through collaborative arrangements with pharmaceutical and biotechnology companies. To find out more about NovaDel Pharma Inc. (AMX: NVD), visit our website at www.novadel.com.

FORWARD-LOOKING STATEMENTS:
Except for historical information contained herein, this document may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve known and unknown risks and uncertainties that may cause the Company's actual results or outcomes to be materially different from those anticipated and discussed herein including, but not limited to, the successful completion of its pilot pharmacokinetic feasibility studies, the ability to develop products (independently and through collaborative arrangements), the ability to commercialize and obtain FDA and other regulatory approvals for products under development and the acceptance in the marketplace for oral spray products. Further, the Company operates in industries where securities may be volatile and may be influenced by regulatory and other factors beyond the Company's control. Important factors that the Company believes might cause such differences are discussed in the risk factors detailed in the Company's most recent Annual Report and Registration Statements, filed with the Securities and Exchange Commission. In assessing forward-looking statements contained herein, if any, the reader is urged to carefully read all cautionary statements contained in such filings. Zanaflex(R) is a registered trademark of Acorda Therapeutics, Inc.

SOURCE: NovaDel Pharma Inc.
NovaDel Pharma Inc. Michael E. Spicer, 908-782-3431 ext. 2550 Chief Financial Officer mspicer@novadel.com
Copyright Business Wire 2008


Except for historical information contained herein, this document contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve known and unknown risks and uncertainties that may cause the Company's actual results or outcomes to be materially different from those anticipated and discussed herein including, but not limited to, the ability to develop products (independently and through collaborative arrangements), and the ability to commercialize and obtain approval for products under development. Further, the Company operates in industries where securities may be volatile and may be influenced by regulatory and other factors beyond the Company's control. Important factors that the Company believes might cause such differences are discussed in the risk factors detailed in the Company's most recent Annual Report and Registration Statements, filed with the Securities and Exchange Commission. In assessing forward-looking statements contained herein, if any, the reader is urged to carefully read all cautionary statements contained in such filings.

Please note that the information in each of the press releases referenced here is only current as of the date of the release. NovaDel Pharma Inc. undertakes no obligation to update the information in the press releases to reflect new information, the occurrence of future events or circumstances, or otherwise.

GW thwarted again

Porton Down, UK, 20 July 2007: GW Pharmaceuticals plc (AIM: GWP) announces that it has chosen to withdraw its current regulatory application for Sativex in Europe and that it expects to resubmit an application for approval in 2008. This follows constructive and detailed discussions with regulatory authorities in which they have provided a clear path to approval for Sativex in the treatment of MS Spasticity.

MS Spasticity Application
In September 2006, GW filed an application for Sativex under the decentralised procedure in four European countries (UK, Spain, Denmark, Netherlands) for the relief of MS Spasticity. GW has been able to resolve successfully all the major questions raised by the regulators during this process except one, and at a meeting with the UK assessors this week, it became clear that this outstanding issue requires the generation of additional data. As European regulatory rules do not permit the introduction of new data as part of the current process, GW has elected to withdraw and resubmit its application.

The current regulatory application process has confirmed that quality and safety data are already sufficient to support a marketing authorisation of Sativex. The regulators have also confirmed that existing efficacy data provide statistically significant evidence and “could in principle lead to a positive risk benefit conclusion”. In addition, regulators have recognised that a large proportion of otherwise treatment-resistant patients respond to Sativex by obtaining clinically meaningful improvements in spasticity.

Sativex provides benefit to the most high need MS patients who have no further therapeutic options available. The regulator’s outstanding clarification relates to the fact that in a clinical trial context, the benefit obtained by “responders” can be masked by looking at the mean improvement across the whole studied patient population, which comprises both responders and non-responders. The regulators therefore wish to be able to identify Sativex responders in the first 4 weeks of treatment and to confirm that the improvements gained by such responders over a further 12 week period is significantly greater than placebo.

As part of the current regulatory process, GW performed analyses of existing data showing that responders can be reliably identified after 4 weeks and that, after 12 weeks, the difference from placebo is clinically important and highly statistically significant (p=0.015). The regulators view this as acceptable evidence of efficacy in principle but consider these analyses technically to be “post-hoc” since they were performed at the regulator’s request following completion of the trials. They require such data to be produced as part of a prospectively planned analysis and hence GW will undertake an additional study to re-confirm this result prior to resubmitting its regulatory application.

The regulators have given GW clear guidance as to the design of the further study required, which differs from a conventional Phase III design. The study is expected to start recruiting patients in the next few months, with the results due in the second half of 2008. The regulators have specified a novel “enriched design” which first identifies responders over a 4 week period, and then focuses on analysing the effect of Sativex vs placebo on those responders over a further period of time.

GW’s clinical plans for the next twelve months have for some time included a further MS Spasticity trial and the regulator’s specific design requirements will therefore be incorporated into the planned study. This study is already within GW’s budget for 2008, will not result in any increase in rate of R&D expenditure above current levels and will be financed from existing cash resources, which today stand at £19.5m.

Sativex Resubmission
There are two potential opportunities for early re-submission in Europe next year. In the indication of MS Neuropathic Pain, a second pivotal Phase III trial completes in early 2008 which could lead to a regulatory filing in this indication at that time. Since this is a distinct indication from MS Spasticity, the outstanding issue identified as part of this recent application would not be relevant. In the event that GW does not submit for this indication, the second opportunity is to resubmit for MS Spasticity later in 2008 following completion of the new study outlined above.

Dr Stephen Wright, R&D Director, said, “We are encouraged that the regulators see Sativex as providing useful efficacy and that they accept our quality and safety data as sufficient for approval. This regulatory application has provided us with a clear route to approval for Sativex in the relief of MS Spasticity. We have received detailed and constructive guidance from the regulators on how to satisfy their single outstanding requirement and are confident that we can address this.

“We expect to re-submit our application to the regulators in Europe in 2008, either in the indication of MS Neuropathic Pain or MS Spasticity. Elsewhere, we look forward to receiving final regulatory approval in Canada for the Cancer Pain indication in the coming weeks and our first large scale clinical trials in the US are scheduled to commence in the late summer.”

Professor Mike Barnes, President of the World Federation of Neuro-rehabilitation, Professor of Neurological Rehabilitation and Consultant Neurologist, University of Newcastle, said, “The data clearly show that Sativex provides valuable and much needed relief of MS Spasticity. Indeed, this medicine is able to treat some of the highest need MS patients, who currently have no further treatment options available. It is regrettable and unnecessary in my view, and in the view of other prominent members of the MS treatment community, that the regulators require GW to generate further data to show what we already know – that Sativex is a safe and efficacious treatment for people with MS.”

Dr Geoffrey Guy, GW Chairman, said, “We recognise that it is taking longer than we had hoped for Sativex to obtain approval in Europe. Each step, however, has been one of progress towards achieving this goal. Whilst we complete these final steps, we will continue to respond to the needs of people with MS by ensuring Sativex remains available under our named patient prescription programme.”

There will be a conference call for analysts today at 8.30am BST. Analysts should contact Gemma Cross Brown at Financial Dynamics on +44 (0) 20 7831 3113 for details. There will be a live audio web cast of this call, which will be accessible on the press releases page in the investor relations section of the GW website (www.gwpharm.com). A recording of this call will be available on the GW website later today.

Enquiries:

GW Pharmaceuticals plc Today: +44 20 7831 3113
Dr Geoffrey Guy, Chairman Thereafter: +44 1980 557000
Justin Gover, Managing Director
Mark Rogerson, Press and PR Tel: +44 7885 638810

Financial Dynamics Tel: +44 20 7831 3113
David Yates, Ben Atwell
About Sativex

Sativex is being developed for approval in four target indications (MS Spasticity, MS Neuropathic Pain, Cancer Pain and Peripheral Neuropathic Pain). Each of these indications provides a distinct regulatory opportunity and is supported by a specific clinical development programme.

In Canada, Sativex is approved for the relief of MS Neuropathic Pain and has also received a Qualifying Notice from the Canadian regulators for a further approval in the relief of Cancer Pain. Final approval of the Cancer Pain indication is expected shortly.

In the United States, the lead indication for Sativex is Cancer Pain and, following a series of positive meetings with the Food & Drug Administration (FDA), late stage trials in that country are about to commence.

GW has to date entered into three Sativex license agreements – with Otsuka in the US, with Bayer HealthCare in the UK and Canada, and with Almirall in Europe (ex-UK). These agreements together have yielded financial terms to GW totaling $51m of signature fees, up to $376m of milestone payments as well as significant long term supply price provisions.

About GW

GW was founded in 1998 and listed on the AiM, a market of the London Stock Exchange, in June 2001. Operating under license from the UK Home Office, the company researches and develops cannabinoid pharmaceutical products that alleviate pain and other neurological symptoms in patients who suffer from serious ailments. GW has assembled a team of over 100 scientists with extensive experience in developing both plant-based prescription pharmaceutical products and medicines containing controlled substances. GW occupies a world leading position in cannabinoids and has developed an extensive international network of the most prominent scientists in the field. For further information, please visit www.gwpharm.com

This news release may contain forward-looking statements that reflect GWs current expectations regarding future events, including development and regulatory clearance of the GW's products. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including (inter alia), the success of the GW's research strategies, the applicability of the discoveries made therein, the successful and timely completion of uncertainties related to the regulatory process, and the acceptance of Sativex and other products by consumer and medical professionals.

Avigen Receives Approval to Initiate AV650 Phase II Clinical Development

Avigen to Present at Cowen and Company Annual Health Care Conference

Webcast Scheduled for 9:30 a.m. (ET) on Thursday, March 15, 2007

ALAMEDA, Calif., March 14, 2007 (PRIME NEWSWIRE) -- Avigen, Inc. (Nasdaq:AVGN) a biopharmaceutical company developing innovative therapies for the treatment of neurological conditions, today announced it was given approval from the U.S. Food and Drug Administration to commence Phase II clinical development of AV650 (tolperisone). AV650 is a New Chemical Entity (NCE) in the United States. Tolperisone is approved in several EU member countries for the treatment of spasticity and muscle spasms. Avigen's initial Phase II trial will assess the safety, tolerability, and initial efficacy, as well as AV650's lack of sedation, in spinal cord injury patients suffering from spasticity. This study will be a multi-center, double-blind, placebo-controlled trial and will explore doses up to the EU approved dose of 450 mg per day.

"This is an important step for Avigen and for the clinical development of AV650 for the treatment of spasticity," said Avigen President and Chief Executive Officer Kenneth Chahine, Ph.D., J.D. "It signifies not only the first time that AV650 is studied in the United States, but also the first time that lack of sedation will be formally assessed in patients with spasticity.

"This trial is part of Avigen's overall development plan for AV650," added Chahine. "Going forward, we intend to study AV650 at higher doses and in a variety of patient populations to fully explore its efficacy and safety profile."

Patricia Nance, M.D., clinical professor, Department of Physical Medicine and Rehabilitation, University of California, Irvine noted, "Many patients suffering from spasticity find it difficult to tolerate currently available therapies due to sedation and other factors. We are encouraged by the European experience with AV650 and the promise that AV650 can provide patients relief of spasticity symptoms without the limiting side effects associated with these therapies."

About AV650

AV650 is being developed in the North American market for the treatment of disabling neuromuscular spasticity and spasm under a license and supply agreement with Sanochemia Pharmazeutika AG. AV650 is an orally administered centrally acting small molecule marketed for the treatment of neuromuscular spasticity and spasm in Europe and Asia, including Germany, Switzerland, Austria, and Japan. Avigen's development program will build on the extensive ex-U.S. safety and efficacy experience with this compound.

About Neuromuscular Spasm and Spasticity

Chronic or recurrent muscle spasm is a sudden, violent, painful contraction of muscles typically associated with serious neurological disorders such as Lou Gehrig's disease (ALS), multiple sclerosis, stroke, spinal cord injury, and cerebral palsy. These painful muscle spasms are often, but not always, associated with spasticity, an abnormality in muscle "tone." Spastic limbs become stiff and rigid because the muscles fail to relax, lacking normal regulation by the damaged nervous system. Both spasticity and sudden, painful muscle spasms can occur as complications of the neurological disorders mentioned above.

About Avigen

Avigen is a biopharmaceutical company focused on unique small molecule therapeutics and biologics 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 committed to its small molecule and biologics neurology products. The company currently has in development AV650 for neuromuscular spasm and spasticity and AV411 for neuropathic pain. Additionally, the company has in development a compound for the treatment of hemophilia A and B, AV513. For more information about Avigen, consult the company's website at http://www.avigen.com.

Statement under the Private Securities Litigation Reform Act

This press release contains forward-looking statements, which include, among others, statements relating to Avigen's intention to study AV650 at doses higher than 450 mg per day in a variety of patient populations, its belief that AV650 may be able to provide patients relief of spasticity symptoms without the limiting side effects associated with other therapies, its belief that it will be able to build on ex-U.S. Tolperisone safety and efficacy experience, and its intention of completing the requirements of clinical development for each of the candidates in its product pipeline; looking for opportunities to expand its pipeline through a combination of internal research, acquisitions, and in-licensing; 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 September 30, 2006, under the caption "Risk Factors" in Item 1A of Part 2 of that report, which was filed with the SEC on November 2, 2006.

Webcast

Michael Coffee, Chief Business Officer, will present information about Avigen's AV650 development plan at Cowen and Company's 27th Annual Health Care Conference on Thursday, March 15, 2007, from 9:30 to 10:05 a.m. ET. The presentation will be webcast live and archived on Avigen's website at www.avigen.com.

The Avigen, Inc. logo is available at http://www.primezone.com/newsroom/prs/?pkgid=2981

This news release was distributed by PrimeNewswire, www.primenewswire.com

SOURCE: Avigen, Inc.

Avigen, Inc.
Michael Coffee, Chief Business Officer
(510) 748-7372
Fax: (510) 748-7155
ir@avigen.com
http://www.avigen.com
1301 Harbor Bay Parkway,
Alameda, CA 94502