Positive Sativex® Study Confirms Long Term Efficacy in MS Neuropathic Pain

08/09/2008

Results Support Designof Ongoing Phase III MS Spasticity Study

Porton Down, UK, 8 September 2008: GW Pharmaceuticals plc (GWP:AIM) announces positive results from a placebo-controlled “randomized withdrawal” study of Sativex® in patients with neuropathic pain due to Multiple Sclerosis (MS). This study design is described by regulators as being sufficient to satisfy the need for long-term efficacy data.

This randomized withdrawal study evaluated 42 MS patients with central neuropathic pain who had previously been in a Sativex Phase III MS neuropathic pain study and who continued to take Sativex on an open label basis for 12 weeks. They were then randomized to Sativex or placebo for a further 4 weeks in a double-blinded manner. During the randomized period, patients were not permitted to adjust their dose. The purpose of this blinded 4-week “randomized withdrawal” study was to assess the maintenance of pain control in patients who remain on Sativex versus those who switch to placebo.

In the patients who were randomized to Sativex pain scores remained stable. In the patients randomized to placebo, pain and sleep scores deteriorated. The prospectively defined primary efficacy endpoint of the study - the time to treatment failure - was statistically significantly in favour of Sativex (p=0.036). The difference between Sativex and placebo was also significant for mean pain score (p=0.028) and sleep quality (p=0.015). The results of all other symptom-related endpoints showed that Sativex patients maintained or improved their response whilst the symptoms of those who switched from Sativex to placebo worsened in the 4 weeks following cessation of active treatment. During the randomized withdrawal period, there were 2 patients with adverse events on Sativex, and 5 on placebo. One patient on placebo withdrew from the study. There was no evidence of any withdrawal syndrome.

Until now, all the evidence for long-term maintenance of efficacy of Sativex has come from long-term open-label exposurei. The results reported today confirm in the context of a placebo-controlled double-blind study that efficacy is indeed maintained in long-term use.

The results of this study are of further significance to GW since the design bears important similarities to the ongoing Phase III MS spasticity study requested by the UK regulator prior to granting approval for Sativex. This ongoing Phase III study involves all patients receiving Sativex for 4 weeks, following which Sativex responders are randomized to continue on Sativex or switch to placebo for a further 12 weeks. This study is due to report results in Q1 2009 with a regulatory submission targeted for H1 09.

Dr Stephen Wright, GW’s R&D Director, said: “This is the first placebo-controlled study showing that Sativex provides long term efficacy for MS patients with neuropathic pain and supplements previously published open-label studies. In addition, these results support the design of the ongoing Phase III trial in MS spasticity. It is encouraging to note that if the difference between Sativex and placebo achieved in the results today are replicated in the ongoing Phase III MS spasticity study, this Phase III study will meet its objectives.”

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 / John Dineen



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.

iRog DJ et al. Clinical Therapeutics. 2007; 29: 2068-2079

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

Sativex® Commences US Phase II/III Clinical Trial in Cancer Pain

26/11/2007

London, UK; Tokyo, Japan; 26 November 2007: GW Pharmaceuticals plc (AIM: GWP) and Otsuka Pharmaceutical Co., Ltd. today announced that the first US Phase II/III dose-ranging trial has been initiated to evaluate the efficacy and safety of Sativex® in the treatment of pain in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy.

The principal investigator of this study is Dr. Russell K. Portenoy, Chairman of the Department of Pain Medicine and Palliative Care at Beth Israel Medical Center in New York City. This five-week, placebo-controlled study will include approximately 40 centers primarily in the US and recruit a total of 336 patients. Patients enrolled in this study must have advanced cancer for which there is no known curative therapy and have a clinical diagnosis of cancer-related pain, which is not wholly alleviated with their current opioid treatment. The primary objective of the study is to evaluate the potential role and dose range of Sativex in these patients as an adjunct to their pre-existing pain medications. The primary endpoint of the study will be the response rate for patients at the end of 5 weeks of therapy, as defined by a 30% or greater reduction in the 11-point, Numeric Rating Scale (NRS).

Commenting on the importance of this study, Dr. Portenoy, said, “Studies suggest that more than one-third of patients with cancer, and more than three-quarters of those with advanced disease, have chronic pain. Large surveys indicate that optimal opioid therapy does not yield sufficient relief in a substantial proportion of these patients. There is a clear need for new treatments to improve these outcomes and it is our hope that cannabinoid formulations may represent an important option in the future. This US-based study is a welcome step in assessing the role of Sativex® as a potential new treatment for cancer pain."

Dr Geoffrey Guy, GW’s Chairman, said, “GW has spent many years preparing for the US development of Sativex® and has established open and positive interactions with relevant federal agencies. The start of the first large scale US clinical trial is a major milestone for the company and for the future prospects for Sativex®. We are delighted to be working in close collaboration with our partner, Otsuka, in advancing Sativex® toward the goal of obtaining US regulatory approval."

Dr. Taro Iwamoto, President of Otsuka Pharmaceutical Development and Commercialization, Inc., likewise noted that “Otsuka is very excited to be working with GW Pharmaceuticals for the development of this potential alternative approach to the treatment of advanced cancer pain. The initiation of this US clinical trial for Sativex is consistent with our mission to develop products for better health.”

Sativex® is an investigational new product composed primarily of two cannabinoids: CBD (cannabidiol,) and THC (delta 9 tetrahydrocannabinol). Sativex® will be administered as a metered dose oro-mucosal spray each 100µL spray contains 2.7mg THC and 2.5mg CBD. The Sativex® formulation is standardized by both composition and dose and is supplied in small spray vials. The components of Sativex have been shown to bind to cannabinoid receptors that are distributed throughout the central nervous system and in immune cells.

This Phase II/III dose ranging study will attempt to replicate and extend data from a previous, two-week clinical trial in 177 patients conducted in Europe. In this European study, Sativex® was administered to patients with terminal cancer and persistent pain that was not fully relieved by current strong opioid therapy. The primary endpoint of this study was the change from baseline to endpoint in the NRS pain score. Sativex, as adjunctive treatment to strong opioid therapy, was associated with a larger decrease in NRS score than was placebo and strong opiods (p=0.014). In addition, 43% of patients who received Sativex®, while remaining on opioids, exhibited at least a 30% decrease in their pain score compared to 21% of patients receiving placebo and opioids (p= 0.024)

Treatment related adverse events in this study were reported by 85% of patients receiving Sativex and by 75% of patients receiving placebo. The most common adverse events (> 10%) reported by patients in this study were somnolence (15% Sativex® vs. 13% placebo); nausea (12% Sativex® vs. 11% placebo) and dizziness (12% Sativex® vs. 5% placebo). Serious adverse events reported by more than one patient receiving Sativex were urinary retention (n=2) and progression of the underlying cancer (n=6).
Enquiries:

For GW:
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

For Otsuka: US Inquiry
Debbie Kaufmann Tel: +1 240 683 3568
Japan Inquiry
Hideki Shirai siraih@otsuka.jp

Notes to Editors

About GW-Otsuka

On 14 February 2007, GW and Otsuka entered into a major long term strategic alliance. The relationship commenced with the signing of an exclusive license agreement to develop and market Sativex® GW’s lead product, in the US. Under this agreement, GW and Otsuka jointly oversee US clinical development and regulatory activities as well as the commercialization strategy. GW is responsible for carrying out the US clinical development program, the costs of which are borne by Otsuka. Otsuka will be responsible for the marketing and sales activities in the US.

On 9 July 2007, GW and Otsuka signed a global research collaboration for the study of cannabinoids in the field of Central Nervous System (CNS) and oncology to research, develop and commercialize a range of candidate cannabinoid products.

About Otsuka Pharmaceutical Co., Ltd

Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka - people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and consumer products for the maintenance of everyday health. Otsuka is committed to being a corporation that creates global value, adhering to the high ethical standards required of a company involved in human health and life, maintaining a dynamic corporate culture, and working in harmony with local communities and the natural environment.

The Otsuka Pharmaceutical Group comprises 99 companies and employs approximately 31,000 people in 17 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned US$7.2 billion in annual revenues in fiscal 2006.

Focusing on the central nervous system, the circulatory, respiratory, and digestive systems, ophthalmology and dermatology, Otsuka’s pharmaceutical product business engages in the research and development, manufacture and sale of pharmaceuticals, aiming to maximize the assets of a global network to address unmet medical meets.
For additional information, visit www.otsuka-global.com

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.

New Published Study Shows Sativex® Successfully Treats Neuropathic Pain

12/11/2007

Porton Down, UK, 12 November 2007 - GW Pharmaceuticals plc (AIM: GWP) today announces that The International Association of the Study of Pain has published online the results of a study in its official journal Pain, showing that Sativex® successfully treats peripheral neuropathic pain1.

The trial was a multi centre, double-blind, randomised, placebo-controlled parallel group study, conducted in 125 patients with peripheral neuropathic pain characterised by allodynia. The publication of these data follows the previous announcement of preliminary results of this study.

In the study, Sativex demonstrated significant superiority to placebo in reducing pain, as measured on a 0-10 Numeric Rating Scale (p=0.004), the primary endpoint of the study. Statistically significant improvements were also seen in the Neuropathic Pain Scale composite score (p=0.007), sleep disturbance (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patients Global Impression of Change (p<0.0001).

Sativex was well-tolerated in this study, with the majority of adverse events being mild or moderate. There were no treatment-related serious adverse events.

The five week trial was conducted in patients who were experiencing significant levels of neuropathic pain and who had failed to gain adequate relief from currently available analgesic medications. Patients enrolled in the study continued to take their existing medication throughout the trial. Sixty-nine percent of patients were taking opioid analgesics. Hence, improvements obtained on Sativex were over and above those obtained on currently available treatments.

Professor Turo Nurmikko, Principal Investigator, Professor of Pain Science and Consultant Pain Physician at the Walton Centre for Neurology and Neurosurgery, Liverpool, commented, "Peripheral neuropathic pain can be extremely disabling and is one of the most difficult types of chronic pain to treat. This study demonstrates that Sativex is effective in the relief of peripheral neuropathic pain. In particular, considering the refractory nature of their pain and that patients remained on their existing analgesia, the improvements seen on Sativex are very encouraging."

Dr Stephen Wright, Director of Research & Development at GW, noted "We are pleased that this important study has been published in Pain, a highly regarded and influential journal. This recognition of the high quality of GW clinical research and of the importance of these findings provides further evidence of the utility of Sativex in the relief of neuropathic pain, an area of significant unmet medical need."

This study is part of a broad programme of clinical trials aimed at securing future regulatory approval for Sativex in neuropathic pain. It is intended to conduct further Phase III clinical trials targeted at neuropathic pain following initial regulatory approval for Sativex in Multiple Sclerosis in Europe.

- ends -

Enquiries:

GW Pharmaceuticals plc Today: +44 (0)20 7831 3113
Dr Geoffrey Guy, Executive Chairman
Justin Gover, Managing Director
Dr Stephen Wright, R&D Director

Financial Dynamics Tel: +44 (0)20 7831 3113
David Yates, Ben Atwell
Notes to Editors

Sativex®
Sativex (THC:CBD), an endocannabinoid system modulator, is derived from whole plant extracts of two specifically bred cannabis plant varieties. The extracts are combined to produce a standardised formulation containing two major components of cannabis, the cannabinoids D9-tetrahydrocannabinol(THC) and cannabidiol(CBD).

Sativex is formulated into a pump action oromucosal (mouth) spray designed for self-administration by the patient. This formulation allows for flexible dosing, ideal for the variable nature of MS. Each spray of Sativex delivers a fixed dose of 2.7mg THC and 2.5mg CBD. Sativex was generally well tolerated in the study.

Allodynia
Allodynia is the occurrence of pain in response to a normally non-painful stimulus (e.g. clothes touching against the skin). It is often intense and can occur in patients suffering from a range of conditions that damage the peripheral nerves (e.g. diabetes, post-herpetic neuralgia) and is a highly reliable marker of neuropathic pain. Neuropathic pain can be difficult to diagnose and may be confused with nociceptive pain (caused by bodily injury - 'visceral' or 'somatic'). The presence of allodynia can confirm that the pain experienced by the patient is truly neuropathic.

Neuropathic Pain
Neuropathic pain is caused by damage to or dysfunction of the nervous system. It is usually chronic and accompanied by unpleasant burning or shooting sensations, or extreme sensitivity to touch. The classification of central or peripheral neuropathic pain is determined by the location of the damage or dysfunction in the nervous system.
It is estimated that at least 1 per cent. of the world's population suffers from neuropathic pain, including over 600,000 patients in UK.
Neuropathic pain can be associated with many conditions including multiple sclerosis, stroke, cancer, spinal cord injury, physical trauma and peripheral neuropathy resulting from diabetes. It can also occur in patients who have previously suffered from shingles, a condition known as post-herpetic neuralgia.
Neuropathic pain is one of the most difficult types of chronic pain to treat. Since treatment options are limited, doctors often prescribe a combination of therapies in an attempt to relieve symptoms.

GW Pharmaceuticals plc
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

References

1. Nurmikko T, Serpell M, et al. Sativex Successfully Treats Neuropathic Pain Characterised by Allodynia: a Randomised, Double-Blind, Placebo-Controlled Trial. Pain. 2007: doi:10.1016/j.pain.2007.08.028M

MHRA stalls cannabis-based MS drug

By Anna Lewcock

23/07/2007 - A UK firm developing cannabis-derived multiple sclerosis (MS) treatments has decided to pull an EU application for its lead candidate Sativex, following demands by UK regulators for additional data in support of the treatment.

Despite the fact that there are no quality or safety issues standing in the way of approval for GW Pharmaceuticals' MS spasticity treatment Sativex, and clinical efficacy data showing promising and statistically significant results, the Medicines and Healthcare products Regulatory Agency (MHRA) has requested an 'enriched design' study be carried out focussing on specific patients who respond to the treatment.

MS specialist Professor Mike Barnes of the University of Newcastle criticised the regulator's "bureaucratic approach," claiming it is "regrettable and unnecessary…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."

The stumbling block in the approval process has been caused by the fact that Sativex is intended for patients who have exhausted all other treatment options, which means that some subjects simply lack the ability to respond to the the drug, or any other MS treatment.

"That translates in a clinical trial setting into a situation where…patients who do respond [are] masked by the lack of response in those patients who simply don't have the capacity to respond," explained Stephen Wright, R&D director at GW.

As such, the MHRA has asked GW to carry out confirmatory studies looking only at patients showing a response to Sativex, and to identify the level in response in this set of subjects. Although the company carried out analysis of existing data through which responders were found to be easily identifiable, as well as 62 per cent more likely to achieve a meaningful response than on placebo, the MHRA has put its foot down and demanded more data be generated before the drug can be approved.

"Analyses show we can very reliably identify responders after four weeks of treatment," said Wright.

"From the regulator's point of view that is very encouraging, but from a technical point of view they have a requirement that those analyses be carried out in a prospective way rather than in a 'post-hoc' analysis."

GW had planned to carry this type of study further down the line anyway, and as such is already well-prepared to carry out the confirmatory study. The first patients should be able to enter the trial in October this year, with completion expected in around 12 months time.

The company has two options for resubmission in the EU following the decision to withdraw its application last week. A second pivotal Phase III trial of Sativex for the treatment of MS neuropathic pain is due to complete in early 2008, which could lead to a regulatory filing around that time. As the outstanding issue regarding efficacy in responders relates to an indication of MS spasticity, it should not affect the pain application.

Should GW not submit an application for the neuropathic pain indication, the company's next opportunity is to submit for MS spasticity in the second half of 2008 following completion of the additional study.

"It's quite clear from our discussions with [the MHRA] that this enrichment study, providing it's positive, will result in the approval of Sativex," said Wright.

Sativex is GW Pharmaceutical's first product, and is being developed for approval in four target indications: MS spasticity, MS neuropathic pain, cancer pain and peripheral neuropathic pain.

The treatment is based on extracts taken from the widely-used recreational drug cannabis, and applied as an oro-mucosal spray to the mouth. It is based on a combination of two well-characterised cannabinoids (chemical compounds found only in the cannabis plant), delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC has been shown to have analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties, while CBD has shown anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects.

In April 2005 GW received approval for Sativex in Canada, for use as an adjunctive therapy for the relief of neuropathic pain in patients with MS. The company also expects Canadian approval for the relief of cancer pain in the near future.

In the US, cancer pain is the lead indication for Sativex, with the first patients entering pivotal late stage trials next month.

While the drug is yet to be approved anywhere outside Canada, the company has already licensed Sativex to Bayer Healthcare for the Canadian and UK markets and Almirall Prodesfarma for the rest of Europe, as well as Otsuka for the US market. Together, these agreements have generated $51m (€37m) in signature fees, up to $376m in milestone payments, and 'significant' long term supply price provisions.

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.

Cannabis Based Medicine (Sativex®) Relieves Spasms And Stiffness In People With Multiple Sclerosis

Today, a leading neurology journal - European Journal of Neurology (EJN) reports a study1 which shows that Sativex, a cannabis based medicine, significantly reduces intractable spasms and stiffness (spasticity) in people with Multiple Sclerosis (MS).

Spasticity is one of the most common symptoms of MS, occurring in up to 84% of patients1. Spasticity can severely impact quality of life and is one of the most difficult symptoms of MS to treat1.

The study, a randomised, double-blind trial, led by Professor Christine Collin from the Royal Berkshire and Battle NHS Trust, Reading, UK, saw Sativex or placebo added to existing anti-spasticity medication. Sativex demonstrated significant superiority to placebo in reducing spasticity (p<0.05). Further, the addition of Sativex produced a more than 30% improvement in spasticity in 40% of the people treated1.

Fern Andrews, a person with MS who has participated in clinical trials with Sativex, commented: "Spasticity can make the simple daily activities that most people take for granted, seem daunting. Just dressing and moving around the home can be difficult and I often have to rely on a carer for support. With Sativex, I'm able to choose how much I take depending on how bad my symptoms are - which is a real benefit".

Christine Jones, Chief Executive of the MS Trust said, "Effective relief of spasticity is extremely important to people with MS. Spasticity and muscle spasms are not only distressing and painful, they can have a negative impact on quality of life. The results of this study add to the growing body of evidence that cannabis-based medicines can be effective in helping to relieve this common symptom of MS."

About the study published in the European Journal of Neurology:

The six week study was conducted in 189 MS patients, all of whom were experiencing significant levels of spasticity and had failed to gain adequate relief from currently available anti-spasticity medications. Patients enrolled in the study continued to take their existing medication throughout the trial1.

Sativex®:

Sativex (THC:CBD), an endocannabinoid system modulator, is derived from whole plant extracts of two specifically bred cannabis plant varieties. The extracts are combined to produce a standardised formulation containing two major components of cannabis, the cannabinoids D9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

Sativex is formulated into a pump action oromucosal (mouth) spray designed for self-administration by the patient This formulation allows for flexible dosing, ideal for the variable nature of MS. Each spray of Sativex delivers a fixed dose of 2.7mg THC and 2.5mg CBD. Sativex was generally well tolerated in the study.

Sativex has been developed by UK-based GW Pharmaceuticals plc. It is approved as a prescription medicine in Canada for the symptomatic relief of neuropathic pain in adults with MS. Sativex is currently being reviewed by European regulatory authorities for the symptomatic relief of spasticity in MS and, on approval, will be exclusively marketed by Bayer HealthCare in the UK.

Spasticity:

Spasticity results from more than one group of muscles contracting incorrectly, causing spasms or stiffness. Spasms are uncontrollable muscle contractions and can be painful. They can be a particular problem at night causing disruption of sleep. Limbs may shoot away or bend upwards towards the body and severe spasms may make the back arch off the bed or chair.

Stiffness of the limbs is common and can make it difficult to perform normal activities, particularly delicate movements of the hand and fingers. If the leg muscles are affected it can make walking difficult. Pain can be associated with spasticity. Current treatments are often only partially helpful.

About Bayer HealthCare:

Bayer HealthCare, a subsidiary of Bayer AG, is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. The Pharmaceuticals division, Bayer Schering Pharma AG, comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology, Primary Care, and Oncology. Bayer HealthCare's aim is to discover and manufacture products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating diseases. http://www.bayerhealthcare.com

About GW Pharmaceuticals plc:

GW Pharmaceuticals plc is licensed by the UK Home Office to undertake a pharmaceutical research and development programme to develop non-smoked cannabis-based prescription medicines. GW's shares are publicly traded on AiM, a market on the London Stock Exchange.

GW's clinical research program is being carried out by a team of pharmaceutical professionals experienced in drug development and, in particular, the development of plant-based medicines and drug delivery systems. http://www.gwpharm.com

References:

1. Collin C et al. Randomised controlled trial of cannabis based medicine in spasticity caused by Multiple Sclerosis. European Journal of Neurology, March 07