GWP.L Regulatory News (GWP)

8 Apr 2008 07:01

GW Pharmaceuticals PLC08 April 2008 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) announcespreliminary results of a Phase III double-blind randomised placebo-controlledstudy of Sativex(R) in 339 patients with central neuropathic pain due toMultiple Sclerosis (MS), who have achieved inadequate pain relief with existingtherapies. This study is one of three Phase III trials for Sativex underway in 2008, eachof which targets a distinct indication. The other European Phase III study in MSSpasticity, requested last year by the UK regulator in order to gain approval inthis indication and which involves a different trial design, is on track toreport later this year. The primary efficacy endpoint in the study reported today was the proportion ofpatients whose pain reduced by at least 30% as measured on a 0-10 numericalrating scale ("responder analysis"). In this study, 50% of Sativex patientsexperienced a pain reduction of at least 30%, the second largest response rateseen in any Sativex study and amongst the largest seen for any pain treatment inthe published literature. However, although the difference between the Sativexand placebo groups was clearly in favour of Sativex, it narrowly failed to reachstatistical significance in this trial due to an unexpectedly large placeboresponse. Key secondary endpoints followed the same trend - in favour of Sativexversus placebo but not at a statistically significant level due to the very highplacebo response. The placebo response in the study reported today appears related to dosingdesign, 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 Sativexwhereby patients initially experiment with dosing of Sativex to find theiroptimum dose level and which, once established, is usually maintainedthereafter. Analysis of the efficacy data at fixed dose levels demonstrates ahighly significant difference between Sativex and placebo. However, aconsequence of allowing patients to determine their own dose was that patientson placebo took significantly more doses than patients on Sativex, thusconfounding the overall comparison. This validates the decision by GW last yearto adopt a fixed target dose approach in both the ongoing studies of Sativex inMS Spasticity and Cancer Pain. The safety profile of Sativex in this study is superior to that seen in previousstudies. The withdrawal rate due to adverse events was 9% on Sativex vs 6% onplacebo, the lowest seen in long duration Sativex studies. As in previousstudies, the most common adverse event was dizziness. The rate of this adverseevent was less than in previous studies (20% on Sativex vs 8% on placebo ascompared with 32% vs 9%). GW's regulatory strategy is to file Sativex for approval in MS Spasticity inEurope and Cancer Pain in the United States. In Europe, regulatory discussionswith the Medicines and Healthcare products Regulatory Agency (MHRA) haveexclusively focused on MS Spasticity, a distinct indication supported bydifferent clinical trials. Last year, the MHRA provided clear guidance on theadditional clinical trial required for approval. As indicated above, this trialis on track and due to report later this year. Dr Stephen Wright, R&D Director, said: "It is clear from the size of theresponse seen in this study that Sativex provides important improvements forthese high need patients, even those that have failed to respond to all otherpain treatments. It is frustrating that the extent of the placebo response hasnarrowly prevented the benefits seen on Sativex translating into a statisticallysignificant outcome. The design of the MS Spasticity study due to report laterthis year is specifically focused on limiting the potential for placebo responseand we expect the outcome of this trial and our other studies to confirm thebenefits of Sativex." "MS Spasticity is a distinct indication supported by different clinical trialsand the route to regulatory approval for Sativex as a treatment for thisindication remains clear and unaffected by the data announced today." Dr Stuart Ratcliffe, Principal Investigator of the study and most recentlyDirector, Pain Research Group, St Bartholomew's and The Royal London HospitalsNHS 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 thistrial appears to have encouraged an abnormally high placebo response. However,this in no way should detract from the beneficial effects of Sativex seen in thestudy. Patients saw a marked improvement in their symptoms, a highly impressiveeffect since they are treatment resistant, and the study recorded the lowestdrop-out rate, demonstrating the mild side effect profile of Sativex. Myexperience with Sativex continues to show that it is an extremely helpfulmedicine for these high need patients and I am confident that the ongoing trialswhich seek to address the placebo issue will demonstrate its value." Following a comprehensive review of this data, GW intends to carry out a furtherstudy 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. Analystsshould contact Gemma Cross Brown at Financial Dynamics on +44 (0) 20 7831 3113for details. There will be a live audio web cast of this call, which will beaccessible on the press releases page in the investor relations section of theGW website (www.gwpharm.com). A recording of this call will be available on theGW website later today. Enquiries: GW Pharmaceuticals plc (Today) + 44 20 7831 3113Dr Geoffrey Guy, Executive Chairman (Thereafter) + 44 1980 557000Justin Gover, Managing Director Financial Dynamics + 44 20 7831 3113David Yates / Ben Atwell Notes to Editors About GW GW was founded in 1998 and listed on the AiM, a market of the London StockExchange, in June 2001. Operating under license from the UK Home Office, thecompany researches and develops cannabinoid pharmaceutical products for patientswho suffer from a range of serious ailments, in particular pain and otherneurological symptoms. GW has assembled a team of over 100 scientists withextensive experience in developing both plant-based prescription pharmaceuticalproducts and medicines containing controlled substances. GW occupies a worldleading position in cannabinoids and has developed an extensive internationalnetwork 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 ofcurrently available pain treatments, and yet still suffered severe pain, and whoremained on such treatments during the course of the study. Improvements seen inthis study therefore represent benefits over and above that which can beachieved with currently available medication. The study recruited patients inthe UK, Canada, France, Spain and the Czech Republic and the duration oftreatment 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 showedthat 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 responsewas 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 whichrequires a distinct set of clinical efficacy data. These indications are asfollows: • Cancer Pain• MS Neuropathic Pain• MS Spasticity• Peripheral Neuropathic Pain Each of these target indications is supported by existing positive Phase IIIdata and will continue to be supplemented by further late stage trials over thenext few years in order to supplement globally approvable regulatory packagesand 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 NeuropathicPain was the first approved indication, which has now been successfully followedby 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 multipleopportunities over the next few years to obtain approvals for Sativex acrossvarious indications in a number of territories. Footnotes: 1. D.J.Rog, T.J.Nurmikko, T.Friede, and C.A Young. Randomized, controlled trialof cannabis-based medicine in central pain in multiple sclerosis. Neurology2005;65:812 This information is provided by RNS The company news service from the London Stock Exchange