GlaxoSmithKline(GSK) and XenoPort(XNPT) announce agreement on late-stage compound for RLS and neuropathic pain

GlaxoSmithKline (GSK) and XenoPort, Inc. (Nasdaq: XNPT) today announced an exclusive agreement to co-develop and commercialise XP13512, a unique prodrug of gabapentin that improves its bioavailability, in the US and other countries worldwide, excluding certain Asian countries. XP13512 is currently in Phase III development for Restless Legs Syndrome (RLS) and in Phase II development for neuropathic pain. Prior clinical trial results have been encouraging.

XP13512 is a patented, new chemical entity that is designed to improve upon the clinical utility of gabapentin by taking advantage of high-capacity transport mechanisms in the gut to improve absorption.

Under the terms of the agreement, XenoPort is entitled to receive an up-front cash payment of £40 million. XenoPort is also eligible to receive aggregate milestone payments of up to £34 million for development activities leading up to the NDA filing for RLS, up to £111million in other potential development and regulatory milestone payments and up to £153million in potential sales milestone payments based on successful commercialization of XP13512 for RLS and neuropathic pain. In addition to royalties on sales outside the US, XenoPort is entitled to receive tiered, double-digit royalty payments on US sales of XP13512 unless XenoPort elects to co-promote XP13512 with GSK in the US, in which case it will be entitled to participate in a net profit share for XP13512 in the US. If XenoPort decides to co-promote XP13512 in the US, it is also entitled to detail REQUIP products currently in development by GSK, provided they are approved in the US. GSK will have an exclusive right to develop, manufacture and commercialise XP13512 in the US and all countries worldwide except certain Asian countries previously licensed by XenoPort to Astellas Pharma Inc.


In the US, XenoPort will complete the ongoing studies to support RLS development. Subject to positive Phase III clinical data, GSK will file the NDA for RLS for FDA approval. GSK will lead development and registration of XP13512 for all other indications, including neuropathic pain. GSK will also be solely responsible for the manufacture of XP13512 to support its development and commercialization within the licensed territories.


The agreement is subject to review by the US Government under the Hart-Scott-Rodino Act and will become effective after clearing review.


Moncef Slaoui, chairman of R&D, GSK, commented, “This is another important late-stage programme addition to GSK’s R&D pipeline. We are pleased to work with XenoPort toward bringing a new treatment alternative for the management of these two important disease areas of RLS and neuropathic pain where there is still such a large unmet need.”


Ronald W. Barrett, Ph.D., XenoPort’s chief executive officer, stated, “GSK has demonstrated leadership and innovation in educating doctors and patients about the debilitating aspects of RLS and has helped improve the lives of many patients with RLS. We are excited to be collaborating with GSK to advance the development and commercialization of XP13512 and, most importantly, to be creating a new treatment for patients with RLS and neuropathic pain.”


About XenoPort
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort's most advanced product candidate, XP13512, is the subject of this announced alliance with GSK. XenoPort also has a second product candidate, XP19986. Positive Phase IIa results have been reported in patients with Gastroesophageal Reflux Disease (GERD) with XP19986.

GSK: GlaxoSmithKline files its new pre-pandemic influenza vaccine in Europe

GlaxoSmithKline (GSK plc) today announced that its new generation H5N1 split antigen pre-pandemic influenza vaccine has been accepted for review by the Committee for Medicinal Products for Human Use (CHMP) in Europe. This innovative vaccine utilises GSK’s novel proprietary adjuvant system technology which allows a very low amount of antigen (3.8µg) to be used to elicit a strong seroprotective response – the so-called ‘antigen-sparing’ effect.

In a recent pivotal clinical trial carried out in Belgium1 involving the new generation H5N1 influenza vaccine, it was shown that two very low doses of antigen (3.8µg), given 21 days apart, combined with the novel adjuvant system enabled over 80% of individuals to produce a high seroprotective response, a level which exceeds target criteria set by regulatory authorities for registration of influenza vaccines. This ‘antigen-sparing’ phenomenon permits a large number of vaccine doses to be produced for mass vaccination ensuring protection for more people. Furthermore, the magnitude of the immune response to the antigen, in the presence of the novel adjuvant system, is also expected to give protection against ‘drifted’ variants of the H5N1 virus. The vaccine also had an acceptable safety and reactogenicity profile.1

Jean Stéphenne, President of GSK Biologicals, the vaccine division of GSK, commented: “Today’s filing of our new generation pre-pandemic influenza vaccine marks another important milestone in our pandemic preparedness vaccine development programme. I believe the rapidity with which immunogenicity and safety data has been generated resulting in this filing, pays tribute to our ongoing commitment to provide, in as short a timeframe as possible, credible options against the threat of an influenza pandemic.”

“As our new generation pre-pandemic influenza vaccine is also believed to have the potential to offer a cross-protective response the vaccine could be used as part of a proactive pre-pandemic vaccination campaign, giving governments and health authorities the option to initiate vaccination before or at the onset of a pandemic and potentially offering a degree of early protection against the pandemic influenza virus,” added Jean Stéphenne.


GSK are also planning to file the pre-pandemic vaccine in other countries around the world. This new generation vaccine could also be adapted for pandemic use once the causative influenza pandemic strain is identified. Indeed, GSK has already entered into active negotiations with various governments to supply pre-pandemic and/or pandemic influenza vaccines. GSK are also planning to file the pre-pandemic vaccine in other countries around the world subsequently.

Avian influenza
H5N1 avian influenza infections lead to severe disease in both birds and humans. To date, the WHO has reported 267 human cases of avian influenza (H5N1) from 10 countries resulting in 161 deaths2.

Public health experts fear that the H5N1 influenza virus may evolve into a strain that is easily transmitted between people, triggering a worldwide influenza pandemic3. Influenza pandemics are global outbreaks that involve viruses to which humans have little or no immunity.



References:

1. Borkowski A et al. Antigen sparing effect of a novel adjuvant system in a split H5N1 pandemic vaccine. International Vaccines for the World 2006

2. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO(accessed Jan 17, 2007)

3. Global pandemic influenza action plan to increase vaccine supply, WHO
( accessed Jan 17, 2007)

GSK: GlaxoSmithKline awarded $63 million HHS contract for pandemic vaccine research and development: Company begins shipments of its antiviral Relenza

GlaxoSmithKline [NYSE: GSK], one of the world’s largest vaccine manufacturers, has been awarded a contract from the U.S. Department of Health and Human Services (HHS) for the development of pre-pandemic and pandemic flu vaccines. With a value of at least $63.3 million, the contract supports GSK’s ongoing pandemic vaccine research in using the company’s innovative adjuvant technology in combination with antigens to induce a strong immune response.


Under the terms of the contract, GSK will engage in research and development leading towards licensure of antigen-sparing pre-pandemic and pandemic vaccines with adjuvant that will help the US Government extend the limited North American supply of pandemic flu vaccines to protect larger populations in the event a flu pandemic. The 5-year contract also gives the US Government the option to fund an additional $44 million of future clinical development programs related to antigen-sparing pandemic vaccines.


“A limited global supply capacity of flu antigen makes it critical that we use innovative adjuvant system technology to produce a new generation of flu pandemic vaccines,” said David Stout, President of Pharmaceuticals at GlaxoSmithKline. “GSK’s research in adjuvant technology over the past two decades uniquely positions our company to develop adjuvants designed to boost immune response and give broader protection while using smaller amounts of antigen. This award leverages our adjuvant expertise, and supports GSK’s short and long-term vision of helping governments around the world in their pandemic preparedness efforts.”


In a separate action related to pandemic preparedness GSK also announced that the company has begun shipping up to 15.5 million treatment courses of its antiviral Relenza®(zanamivir for inhalation). The Relenza shipments are part of GSK’s agreement with the Federal Government announced last year to provide the US Government and the states with Relenza for building their flu pandemic stockpiles. GSK also has started to ship Relenza to retail pharmacies to fulfill patient prescriptions for seasonal flu treatment and prevention.


GSK’s 2005-2007 Milestones in Pandemic Preparedness

January 2007: GSK begins supplying its antiviral, Relenza® (zanamivir for inhalation), to the U.S.government and begins working with private-sector businesses and other organizations to provide Relenza as part of their business continuity planning.

December 2006: GSK received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for its candidate alum-adjuvanted pandemic vaccine. GSK plans to submit a file to the European regulatory authorities in the coming weeks for the licensing of both a pandemic and a pre-pandemic vaccine with our proprietary adjuvant system technology.

November 2006: GSK received a $40 million initial order for bulk H5N1 antigen from HHS.

2006: GSK signs contracts with several countries for pre-pandemic vaccines.

September 2006: GSK reached an agreement with the Simcere Pharmaceutical Group of Nanjing, China, granting the right to manufacture and sell the anti-viral influenza treatment zanamivir in China, Indonesia, Thailand, Vietnamand all Least Developed Countries.

July 2006: Clinical studies announced by GSK showed promising preliminary results on the potential immunogenicity of a vaccine for pandemic flu using a GSK novel proprietary adjuvant system.

May 2006: GSK received an award of $274 million to develop cell-culture technology to speed the development of new cell culture-based seasonal and pandemic influenza vaccines, and to scale-up cell culture manufacturing capability at GSK’s Marietta, PAsite.


2005: GSK made three important acquisitions in North America: a vaccine manufacturing site in Marietta for cell-culture-based flu vaccines and secondary operations; Corixa Corporation, for its work in developing innovative adjuvants designed to stimulate immunity; and ID Biomedical, which offered a significant increase in flu vaccine manufacturing capacity to help address both seasonal and pandemic influenza threats.

GSK: GlaxoSmithKline receives first European approval for Wellbutrin XR

GlaxoSmithKline announced today that Wellbutrin XR®* (bupropion hydrochloride modified-release tablets), has been granted a marketing license in The Netherlands for the treatment of adult patients with major depressive episodes. The medicine is also considered approvable by the regulatory agencies of 21 other countries** under the Decentralised Procedure.


Wellbutrin XR is the first once-daily noradrenaline dopamine reuptake inhibitor (NDRI) approved for the treatment of Major Depressive Disorder (MDD) in Europe. 1,2,3 Uniquely targeting dopamine and noradrenaline (two chemicals in the brain known to be involved in regulating mood) to treat MDD effectively, Wellbutrin XR offers an alternative to currently available treatments, including Selective Serotonin Reuptake Inhibitors (SSRIs) / Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) which some patients are unable to tolerate due to side effects such as weight gain and sexual dysfunction. 4,5,6,7


“Wellbutrin XR is an important new medicine for doctors and patients in Europe,” comments Andrew Witty, president, GSK Pharmaceuticals, Europe. “Depression can be a crippling condition that is often difficult to treat. With its unique mode of action, Wellbutrin XR offers a real alternative to the depressed patient. We hope its profile will help patients stay on their therapy, which would address a significant unmet need in the area of antidepressants.”


Wellbutrin XR is available as a 300mg or 150mg tablet with a dose of up to 300mg once daily starting with 150mg once daily.


Nearly 13 million patients have been treated with Wellbutrin XR in the USA where it is known as Wellbutrin XL *** and was FDA approved in 2003.5


It is expected that regulatory agencies in various European countries will grant national licenses for Wellbutrin XR throughout the first quarter of 2007, and the medicine could begin to be available to patients from April 2007.


GlaxoSmithKline has an agreement with Biovail Corporation for worldwide sales and distribution of bupropion hydrochloride modified-release tablets.


The most common side effects observed in clinical trials with Wellbutrin XR were trouble sleeping, headache, dry mouth, and upset stomach (nausea and vomiting).8


There is a risk of seizure with Wellbutrin XR , which increases with higher doses. People should not use it if they have had a seizure or eating disorder, or if they abruptly stop using alcohol or sedatives. People should not take Wellbutrin XR with monoamine oxidase inihibitors (MAOIs), or medicines that contain bupropion.



* Wellbutrin XR will be the most common tradename in European countries. Other tradenames include: Elontril (several countries), Voxra (Sweden) and Wellbutrin Retard (Norway).


** Austria, Belgium, Cyprus, Czech Republic, Estonia, Germany, Greece, Hungary, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, and Sweden.


*** While Wellbutrin XL is approved for the treatment of major depressive disorder in the United States, approved conditions of use and labeling may vary from those in European countries.



References


1. Stahl SM. Essential Psychopharmacology. 2nd ed. New York, NY: CambridgeUniversityPress; 2000.

2. Ascher JA et al. J Clin Psychiatry 1995; 56:395—401.

3. Stahl SM et al. Prim Care Companion J Clin Psychiatry 2004; 6:159—166.

4. Jefferson JW et al., J Clin Psychiatry 2006 June; 67(6):865-873.

5. GSK Data on file.

6. Thase ME et al. J Clin Pharmacol 2006; 26(5): 482-488.

7. Zajecka J. J Clin Psychiatry.2001; 62 Suppl 3:35-43.

8. GSK. Wellbutrin XR European Summary of Product Characteristics. 2007.