GlaxoSmithKline and Theravance announce start of large Phase 2B ICS and LABA studies for asthma in the Horizon programme

GlaxoSmithKline Plc (GSK) and Theravance, Inc. (NASDAQ: THRX) today announced the start of large Phase 2b asthma dose-optimisation studies with both the lead inhaled corticosteroid (ICS) GW685698 (‘698) and the lead long-acting beta agonist (LABA) GW642444 (‘444) assets in the ‘Horizon’ programme to develop a next-generation combination product.


GSK began enrolling patients with mild to severe asthma in the ‘698 Phase 2b clinical programme on 21st December 2007and began enrolling patients with persistent asthma in the ‘444 Phase 2b clinical programme on 29th December 2007. These clinical programmes will determine the most effective doses to be taken into Phase 3 combination studies. The Phase 2b COPD programme with ‘444 is also on schedule to commence in 1H 2008.


Darrell Baker, SVP GSK Respiratory Medicines Development Centre said, “The programme is progressing well and we are delighted to have two very strong assets to progress into our large Phase 2b studies.” He continued, “We have seen encouraging results in previous studies and have confidence in our ongoing programme. Both asthma and COPD are serious, debilitating diseases where there remains a considerable unmet need. We believe through this programme we will introduce a meaningful option for the treatment of patients with these conditions.”


“We are very pleased to have met the important milestone of initiating the larger Phase 2b studies with the lead compound ‘444 and with the progress of ‘698," said Rick E Winningham, Chief Executive Officer at Theravance. “Based upon recent clinical and preclinical results, the collaboration’s confidence in the overall profile of ‘444 has increased and we are focusing our resources on this compound to move it forward as quickly as possible. This important step brings us closer to our joint goal of bringing a new treatment option to patients in this important therapeutic area."


These studies will enrol in excess of 2,400 patients recruited globally. The ‘444 LABA Phase 2b dose-optimisation study will enrol approximately 600 patients with persistent asthma who are receiving inhaled steroids. The ‘698 ICS Phase 2b studies will be undertaken in three separate studies in mild, moderate and severe asthma patients with a total enrolment of 1,800 patients. All studies will be carried out using a new inhaler device. In parallel, enabling studies involving ‘444 and ‘698 given in combination will be undertaken prior to commencing large-scale Phase 3 combination studies.


In a recently-completed Phase 2 study, ‘698 demonstrated once-a-day efficacy in patients with moderate asthma, with significant improvements in lung function in excess of 200mL seen within the first two weeks of dosing and maintained throughout the remainder of the 8 week treatment period, without any adverse effect on adrenal function (a marker of systemic steroid effect).


Darrell Baker concluded, “Our goal will be to offer patients the benefit of a once-daily medication to address a significant unmet patient need. As a leader in respiratory medicine, GSK is leveraging years of experience in the development of combination products with the goal of providing physicians and patients with an effective and innovative medicine.”


About GSK
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com.


About Theravance
Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction. Of the six programs in development, four are in late stage – its telavancin program focusing on treating serious Gram-positive bacterial infections with Astellas Pharma Inc., the Gastrointestinal Motility Dysfunction program, the Horizon program (Beyond Advair collaboration) with GlaxoSmithKline plc, and TD-1792 for the treatment of serious Gram-positive bacterial infections. By leveraging its proprietary insight of multivalency toward drug discovery focused on validated targets, Theravance is pursuing a next generation strategy designed to discover superior medicines in areas of significant unmet medical need. For more information, please visit the company's web site at www.theravance.com. THERAVANCE®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of Theravance, Inc.

GSK applies for licence to market OTC weight loss product In Europe

GlaxoSmithKline (GSK) today announced its marketing application for non-prescription orlistat 60mg for weight loss has been accepted for review by the European Agency for the Evaluation of Medicinal Products (EMEA).

Orlistat 60 mg was approved for non-prescription sale in the US by the FDA in February 2007 for use by overweight adults in conjunction with a reduced-calorie, low-fat dietand went on sale there in June 2007 under the brand name alli™. Alli is the only FDA-approved weight-loss product available to consumers without a prescription, and it is the first clinically-proven over-the-counter product to be combined with a comprehensive support programme.

John Clarke, President GSK Consumer Healthcare said: “This is a significant milestone and an important opportunity for GSK. Obesity is a rapidly increasing problem and a significant burden for healthcare systems in Europeand elsewhere. Leveraging our considerable expertise in OTC switches, we hope to offer consumers a new, clinically-proven option which can help to tackle this problem.

“So far, alli is performing well in the US and, if our application is successful, we will commit to rolling out a similar responsible marketing campaign with the same level of support for consumers in Europeas we have done in the US. We want to see people achieving gradual, sustained weight loss by using alli in tandem with a healthy eating, low-fat diet and increased exercise. We’ve said all along that this is no magic pill. If people are looking for a quick fix, this is not it but it is a powerful motivator, helping people lose up to 50% more weight than with diet alone*.”


If the regulatory process is successful, GSK would be granted a licence to market non-prescription orlistat 60mg in all 27 EU member countries, although initial launch markets have not been confirmed.



*- Anderson JW, Schwartz SM, Hauptman J et al. Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial. Ann Pharmacother 2006; 40: 1717-23

- Study BM14149 and study NM14161. GSK data on file.


About Orlistat

§ Orlistat is the most comprehensively studied weight loss medication to date. Its safety and efficacy are well documented and have been established through data from more than 100 clinical studies involving more than 30,000 patients.

One of these studies – for Xenical®** - was the four-year landmark XENDOS trial conducted by Roche, its inventor and manufacturer. In this study alone, over 3,000 people were followed for four years while taking Orlistat, and it isthe longest completed study conducted to date for a weight-loss medicine. In all, since the launch of the 120 mg dose of orlistat as the prescription drug Xenical™ in 1999, there have been more than 28 million patient treatments with orlistat in more that 145 countries worldwide.


§ GlaxoSmithKline completed an agreement with Roche in February 2007 that enables the company to seek regulatory approval for the first non-prescription weight loss medicine in countries outside of the US excluding Japan.


The overweight and obese population in Europe


§ The prevalence of obesity has risen by between 10-50% in the majority of European countries in the last 10 years (International Obesity Taskforce (http://www.iotf.org )


§ Currently almost 400 million adults in Europe are estimated to be overweight and about 130 million to be obese. (WHO 2006; Fact sheet; The challenge of obesity in the WHO European Region http://www.euro.who.int/document/mediacentre/fs1305e.pdf )


§ The average BMI in Europe is nearly 26.5 and overweight affects 25-75% of the adults in Europe. A BMI of 25 and above is overweight and 30 and above is obese. (WHO 2006; Fact sheet; The challenge of obesity in the WHO European Region http://www.euro.who.int/document/mediacentre/fs1305e.pdf


• Obesity and overweight increase the risk of type 2 diabetes, cardiovascular disease, certain cancers, and gallbladder disease, resulting in a decreased quality of life and an increased risk of premature death (WHO 2003; Fact sheet: Obesity and overweight www.who.int/hpr/NPH/docs/gs_obesity.pdf






**Xenical® is a registered trademark of the Roche Group



About GSK

GlaxoSmithKline - one of the world’s leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, please visit www.gsk.com/media

GSK receives decision from FDA on Advair 500/50 for COPD

GlaxoSmithKline announced today that the U.S. Food and Drug Administration (FDA) has issued a not approvable letter for the supplemental drug application for the 500/50 strength of Advair Diskus (fluticasone propionate and salmeterol inhalation powder) in the treatment of patients with chronic obstructive pulmonary disease (COPD).


The FDA questioned how Advair 500/50 compared to the currently approved 250/50 strength in order to allow for appropriate dosing recommendations. GSK will be meeting with FDA to discuss this request in more detail and determine next steps, including discussion of data GSK has recently generated on the reduction of exacerbations with the Advair 250/50 strength.


“We are very surprised and disappointed by this FDA decision particularly given the outcome of the FDA advisory committee meeting earlier this year,” said Katharine Knobil, M.D., Vice-President of Respiratory Clinical Development for COPD at GSK. “The advisory committee voted unanimously that Advair 500/50 demonstrated a significant reduction in the risk of exacerbations. We believe in the strength of the data; this application is based on the results of the largest COPD study conducted in more than 6,000 patients over three years. We are committed to working with the FDA to address any questions they have and to pursue a way forward.”


About Advair in COPD

Advair 250/50 is currently indicated for the maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis. Advair does not replace fast-acting inhalers to treat sudden symptoms. Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids, including fluticasone propionate and Advair Diskus. Patients with COPD often have multiple risk factors for reduced bone mineral density. Advair Diskus may increase this risk, therefore, bone mineral density assessment is recommended prior to starting Advair Diskus and periodically thereafter. Long-term use of inhaled corticosteroids, including Advair Diskus, may increase the risk for cataracts or glaucoma. Regular eye exams should be considered.

For more information about Advair please visit www.gsk-us.com

About GlaxoSmithKline

Advair was developed and is marketed by GlaxoSmithKline, a research based pharmaceutical company and a world leader in respiratory care. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information please visit www.gsk.com.

GSK gives consent under Canada’s Access to Medicines Regime for generic version of HIV/AIDS medicine for use in Rwanda

As part of its broad commitment to improving access to medicines, GlaxoSmithKline today announced it has given consent through Canada’s Access to Medicines Regime to enable a Canadian company (Apotex) to manufacture a generic fixed dose combination (FDC) antiretroviral (ARV), containing two molecules over which GSK has patent rights (zidovudine and lamivudine) for the treatment of HIV/AIDS in Rwanda.


Canada’s Access to Medicines Regime reflects the WTO “31f” agreement of August 2003 and enables the government to authorise the production of certain patented medicines for export. The legislation includes controls which are designed to ensure that these essential medicines reach the patients for whom they are intended and the authorisation to be granted will be subject to these controls. GSK has agreed to waive royalties on the basis that Apotex’s triple combination generic ARV will be supplied on a no profit basis.


Paul Lucas, President and CEO, GSK Canadasaid, “Tackling the AIDS crisis is one of the greatest challenges the world faces. GSK continues to play its part to tackle this crisis through research and development, not-for-profit pricing and ongoing investment in dedicated community programmes. Our decision to allow Apotex to manufacture an FDC containing two GSK molecules is part of this broad commitment. It also shows that Canada’s Access to Medicines Regime operates effectively to enable supply of medicines from Canadaas envisaged under the 31f Agreement.”


About GlaxoSmithKline

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and health-care companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.


GSK has issued eight previously announced voluntary licences to produce generic versions of GSK’s patented HIV/AIDS medicines for patients across Sub-Saharan Africa. In 2006 alone, GSK supplied 86 million tablets of preferentially priced ARVs to developing countries, while over 120 million ARV generic tablets were supplied by companies licensed by GSK.

FDA issues second approvable letter for Trexima

GlaxoSmithKline (LSE & NYSE: GSK) and POZEN Inc. (NASDAQ: POZN) today announced that the U.S. Food and Drug Administration (FDA) has issued a second approvable letter for Trexima™ (sumatriptan/naproxen sodium). An approvable letter is an official notification from the FDA that contains conditions that must be satisfied prior to obtaining final U.S.marketing approval.


In January 2007, POZEN and GSK responded to the FDA’s first approvable letter, submitting additional safety data from clinical trials, data from GSK’s database, and additional in vitro preclinical data. In the second approvable letter, no additional information regarding the cardiovascular safety of Trexima was requested. The companies agreed to conduct a prospective study after approval to evaluate the effects on blood pressure during chronic, intermittent treatment.


The FDA has requested that POZEN further address the Agency’s concern, prior to approval, about the potential implications from one preclinical in vitro chromosomal aberration study (one of four standard genotoxicity assays) in which genotoxicity was seen for the combination of naproxen sodium and sumatriptan, but not with either component alone. None of the other three standard genotoxicity studies (Ames test, mouse lymphoma TK assay, in vivo mouse micronucleus assay) demonstrated any genotoxicity for the combination of naproxen sodium and sumatriptan.


The companies intend to request a meeting with the FDA as quickly as possible to discuss the necessary steps to address the Agency’s concerns.


Trexima was the proposed brand name for the product candidate combining sumatriptan 85 mg, as the succinate salt, formulated with RT Technology™ and naproxen sodium 500 mg in a single tablet. Several new names are under consideration at FDA, but pending a final decision on a new name the product will still be referred to as Trexima.


The FDA had previously determined that Trexima is effective as an acute treatment for migraine headaches. POZEN and GSK will continue to work with the FDA on revisions to the proposed package insert and the proposed trade name.

About Imitrex® (sumatriptan succinate) Tablets

Imitrexis a prescription medication indicated for the acute treatment of migraine in adults. Imitrex should only be used when a clear diagnosis of migraine has been established. Patients should not take Imitrex if they have certain types of heart disease, history of stroke or TIAs, peripheral vascular disease, Raynaud syndrome, or blood pressure that is uncontrolled. Patients with risk factors for heart disease, such as high blood pressure, high cholesterol, diabetes or are a smoker, should be evaluated by a doctor before taking Imitrex. Very rarely, certain people, even some without heart disease, have had serious heart related problems. Patients who are pregnant, nursing, or taking medications should talk to their doctor.

About Naproxen sodium

Naproxen sodium is a non-steroidal anti-inflammatory drug (NSAID) and is contained in Anaprox®, Anaprox DS®, Naprelan®, Aleve® and in a number of over-the-counter medications. Naproxen sodium is indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and juvenile arthritis. It is also indicated for the treatment of tendinitis, bursitis, acute gout and for the management of pain and primary dysmenorrhea. Naproxen-containing products should not be used by patients who have had allergic reactions to any product containing naproxen, nor in patients in whom aspirin or other NSAIDs induce the syndrome of asthma, rhinitis, and nasal polyps. Patients who have a history of peptic ulcer or gastrointestinal bleeding, kidney problems, uncontrolled hypertension or heart failure should consult a physician before using naproxen-containing medications. NSAIDs may cause increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke. This risk may increase with duration of use and in patients with cardiovascular disease or risk factors for cardiovascular disease. Serious gastrointestinal toxicity such as bleeding, ulceration and perforation can occur at any time in patients treated chronically with NSAID therapy and physicians should remain alert for such effects even in the absence of previous GI tract symptoms. Patients who are pregnant or are nursing should consult a physician before use of a naproxen-containing medication.

About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For detailed company information, see GlaxoSmithKline's website: www.gsk.com

GlaxoSmithKline statement in diabetes care study thiazolidinediones and heart failure: a teleo-analysis [1]

This is an analysis of existing data that has been previously published (online in Diabetes Care, 29 May 2007) and provides no new information on the risk of heart failure associated with the thiazolinediones (TZD) class.


“The risk of heart failure in diabetes patients and with use of these medicines is well recognised and is clearly identified in prescribing information to doctors in the UK. Whilst continued patient safety is paramount, we must also remember that Type II diabetes can have devastating consequences including stroke, blindness, amputation and kidney failure. Rosiglitazone therefore has an important role to play as one of the medicines, doctors can use to treat the 2 million patients currently diagnosed with type 2 diabetes in the UK,” said, Dr. Alastair Benbow, European Medical Director, GlaxoSmithKline.


The analysis does not include the results from the ADOPT2 (A Diabetes Outcome Progression Trial) study, and the RECORD3 (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes) interim analysis, two recently published long-term prospective studies in which the risk of heart failure is assessed in patients taking rosiglitazone.


The authors correctly point out that diabetic patients are known to be at increased risk of developing congestive heart failure. The authors also report an increased risk of heart failure with TZD therapy. It is well recognized that this class of medicine can cause fluid retention which may exacerbate or lead to heart failure. This is clearly stated in the European prescribing information for rosiglitazone. In addition, in Europe, rosiglitazone is contraindicated for patients with New York Heart Association (NYHA) Class I-IV cardiac failure or those with a history of cardiac failure. These contraindications have been in the SPC since rosiglitazone was approved in Europein June 2000.

Questions about the safety of rosiglitazone are best answered by long-term prospective studies such as ADOPT and RECORD interim analysis. In ADOPT the same number of congestive heart failure (CHF) serious adverse events were reported for rosiglitazone versus metformin in a drug naive diabetic population. However those on glibenclamide experienced a lower rate of serious CHF events compared to both rosiglitazone and metformin.

In the RECORD interim analysis, rosiglitazone was associated with significantly more cases of CHF when compared with patients on control – metformin and sulphonylurea (hazard ratio 2.24). Despite the increase in CHF however, the primary outcome of cardiovascular hospitalizations and death showed no significant difference between the rosiglitazone group and the met/SU group.

It is important for physicians to use rosiglitazone in appropriate patients in line with the European SPC, which states that rosiglitazone should not be used in patients with CHF. GSK is confident in the overall safety profile of rosiglitazone when used appropriately.


GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.



References


1. Singh et. Al. Thiazolidinediones and Heart Failure: A Teleo-Analysis. Diabetes Care. Published online: 29 May, 2007. Print publication: 27 July 2007

2. Kahn S et al. Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. NEJM 2006 355: 23; 2427-2443



3. Home P D, et al. Rosiglitazone Evaluated for Cardiovascular Outcomes – An Interim Analysis. NEJM 2007: 357: 28-38

GlaxoSmithKline announces Swiss approval of Tyverb®, a new oral treatment for advanced breast cancer

GlaxoSmithKline announced today an important milestone for advanced breast cancer patients across Europe with approval of the first oral ErbB1 and ErbB2 dual inhibitor, Tyverb® (lapatinib). Lapatinib, in combination with capecitabine, received approval from Switzerland’s regulatory authority,Swissmedic,for the treatment of patients with advanced ormetastatic breast cancer whose tumours overexpress ErbB2 (HER-2) and who have relapsed after, or not responded to, trastuzumab therapy.


Lapatinib is a small molecule that is administered orally and works by getting inside the cancer cell and inhibiting two receptor proteins — the tyrosine kinase components of ErbB1 and ErbB2 receptors, which are responsible for tumour growth. This innovative mechanism of action is a new way to treat breast cancer and is different from current targeted therapies for ErbB2 positive disease.


This approval was based on a pivotal Phase III trial (EGF100151) in women with advanced ormetastatic ErbB2 positive breast cancer whose disease had progressed following treatment with trastuzumab and other cancer therapies. The data showed that the median time to progression was 27.1 weeks on the combination of lapatinib and capecitabine versus 18.6 weeks on capecitabine alone (hazard ratio 0.57 (CI 0.43, 0.77) p=0.0001). The response rate was 23.7% versus 13.9% (p=0.017).[1]


The most common adverse events during therapy with lapatinib plus capecitabine were gastrointestinal (diarrhoea, nausea and vomiting) or skin toxicities (hand and foot syndrome and rash). The majority of adverse events and laboratory abnormalities were mild to moderate in severity and were not significantly higher than those seen with capecitabine monotherapy.


"This is an extremely significant and exciting breakthrough for patients and physicians across Switzerland. Lapatinib offers patients an effective, well-tolerated treatment and as an oral therapy offers added convenience for patients. Lapatinib is now available in Switzerland and subject to regulatory approval we remain ontrack to launch lapatinib in the rest of Europe during the second half of 2007" said Paolo Paoletti, SVP and Global Head of the Oncology Medicine Development Centre at GSK. "The approval of lapatinib demonstrates our R&D organisation’s strong commitment to the discovery and development of novel cancer treatments. We are dedicated to the further study and development of lapatinib in a variety of settings including early breast cancer as well as in other types of cancer.”


Brain Metastases as Relapse Site

Brain metastases develop in one third of women with ErbB2 (HER-2) positive metastatic breast cancer, and is an area of significant unmet medical need. Once the disease advances to this site, overall prognosis is poor with the average one-year survival estimated at about 20 percent.[2]

In the Phase III trial on which the Swiss approval is based, preliminary results suggest that lapatinib may play a role in decreasing the development of brain metastases as site of first relapse. CNS relapse were lower in the lapatinib plus capecitabine arm versus the capecitabine alone arm.i Additional studies are ongoing in an effort to confirm this preliminary finding.

Future for Lapatinib - Ongoing Clinical Trials

Further studies are ongoing and are investigating the use of lapatinib either alone or in combination with other therapies for the treatment of breast cancer in women that are ErbB2 positive, including first-line in previously untreated metastatic breast cancer, as well as an adjuvant therapy for primary or early breast cancer. Trials are also ongoing in a range of other solid tumours that overexpress ErbB1 and/or ErbB2, including head & neck and renal cell cancer.[3],,[4]


GSK in Oncology
GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary “bench to bedside” approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes partnerships with more than 160 cancer centres. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.


About GlaxoSmithKline

GlaxoSmithKline — one of the world's leading research-based pharmaceutical and healthcare companies — is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at http://www.gsk.com.


References:
[1] Tyverb® Prescribing Information. GSK data on file.

[2] Weil R. et al. Breast Cancer Metastasis to the Central Nervous System. American Journal of Pathology. 2005;167:913-920.

[3] El-Hariry, I., Harrington K. et al. A phase I, open label study (EGF100262) of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Oral presentation, 1st International Meeting on Innovative Approaches in Head & Neck Oncology, Barcelona, Spain. 22nd - 24th February 2007.

[4] Ravaud A, Gardner, R. Hawkins H et al. Efficacy of lapatinib in patients with high Tumour EGFR expression: Results of a phase III trial in advanced renal cell carcinoma (RCC).Journal of Clinical Oncology, 2006 ASCO Annual Meeting ProceedingsPartI.Vol 24, No. 18S (June 20 Supplement) 2006: 4502.

GlaxoSmithKline: Cervarix is approved in Australia for females 10-45 years old

CervarixTM, the cervical cancer vaccine from GSK, has been granted a licence by the Therapeutic Goods Administration (TGA) of Australia for the prevention of cervical cancer and precancerous lesions associated with the most common cancer-causing human papillomavirus types. CervarixTM is now approved in Australia for use in females aged 10 to 45 years old. This is the first major market licence for CervarixTM, GSK’s cervical cancer vaccine.


“The approval of CervarixTM in Australia is a key milestone towards eradicating the burden of cervical cancer for all women, especially as this is the first cervical cancer vaccine that is explicitly indicated anywhere in the world for women over the age of 26. This vaccine heralds a major scientific breakthrough in cervical cancer prevention and demonstrates GSK’s commitment to developing innovative vaccines. It is great news for us and this vaccine will be a key driver in GSK’s future growth,” said Jean Stephenne, President of GlaxoSmithKline Biologicals.


CervarixTM is formulated with a novel proprietary adjuvant system called AS04 which is designed to enhance immune response and increase the duration of protection. Published data have shown that this adjuvant formulation provides a stronger and longer-lasting immune response compared to the same vaccine composition formulated with conventional aluminum hydroxide adjuvant alone5. Jean Stephenne added, “We are especially excited about CervarixTM, the first cervical cancer vaccine to feature one of our novel adjuvant systems. Our goal is to provide the best possible protection for women against cervical cancer.”


CervarixTM has been tested in over 40,000 females in clinical trials and, in these trials, CervarixTM showed consistently high levels of efficacy in preventing precancerous lesions due to cancer-causing virus types 16 and 181. In findings from these clinical trials, CervarixTM has been shown to have a good safety profile and to be generally well-tolerated in women6,7,8. Data also showed preliminary evidence of additional protection against infection with cancer-causing virus types other than virus types 16 and 181.


GSK submitted a Biologics Licence Application (BLA) for CervarixTM to the U.S. Food and Drug Administration (FDA) in March 2007, following earlier regulatory filings with the European Medicines Agency(EMEA) and regulatory filings in Africa, Asia and Latin America.


Cervical cancer is the second leading cause of cancer in women under 45, and causes over 270,000 deaths worldwide per year2. It occurs when infection with the human papillomavirus becomes persistent, and progresses to cancer. Up to 50-80 per cent of women will acquire an infection in their lifetime, with the risk of persistence increasing with age3. This is why it is so important to ensure that women over 26 are also protected against cancer-causing virus types, to reduce the risk of infection becoming persistent and progressing to cervical cancer. In humans, approximately 100 types of HPV have been identified to date and, of these, approximately 15 virus types are considered to cause cervical cancer. Virus types 16 and 18 are responsible for approximately 70 percent of cervical cancers globally4.



About CervarixTM
CervarixTM is a trade mark of the GlaxoSmithKline group of companies.

CervarixTM, GSK’s cervical cancer vaccine, was developed to prevent infection and lesions from the two most prevalent cancer-causing human papillomavirus types, specifically types 16 and 18. It is formulated with the proprietary adjuvant system, AS04, selected to ensure that this vaccine confers strong and sustained antibody levels over time.


About GlaxoSmithKline
GlaxoSmithKline—one of the world’s leading research-based pharmaceutical and healthcare companies—is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, please visit www.gsk.com/media


GSK Biologicals (GSK Bio), one of the world’s leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline’s activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination pediatric vaccines which protect the world’s children with up to six diseases in one vaccine.




References

1 Harper et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367: 1247-1255

2 Ferlay J, Bray P, Pisani P, et al. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 2.0. IARCPress, Lyon, 2004. Available at: http://www-dep.iarc.fr. Accessed 30 March, 2007

3 Bosch FX, de Sanjose S. Chapter 1 : Human papillomavirus and cervical cancer – burden and assessment of causality. J Natl Cancer Inst Monogr, 2003; 3-13

4 Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348: 518-527

5 Giannini SL, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminum salt combination (AS04) compared to aluminium salt only. Vaccine 2006 24: 5937–5949

6 Gall SA, et al. Substantial impact on precancerous lesions and HPV infections through 5.5 years in women vaccinated with the HPV-16/18 L1 VLP AS04 candidate vaccine. Presented at the American Association for Cancer Research (AACR) annual meeting on 14-16 April 2007 (abstract no. 4900)

7 Schwarz T, Dubin G, et al. Human Papillomavirus (HPV) 16/18 L1 AS04 Virus-Like Particle (VLP) Cervical Cancer Vaccine is Immunogenic and Well-Tolerated 18 Months After Vaccination in Women up to Age 55 Years. Presented at ASCO Annual Clinical Meeting. June 2007.

8 Rombo L, Dubin G. Long-term safety and immunogenicity of a cervical cancer candidate vaccine in 10-14-year-old adolescent girls. Presented at the European Society of Paediatric Infectious Diseases (ESPID) annual meeting on 2-5 May 2007

Cervarix data show that higher levels of antibodies in the bloodstream correlate to higher levels in cervico-vaginal secretions

New data in women 15 to 55 years of age show that the GlaxoSmithKline (GSK) cervical cancer candidate vaccine induces an immune response to cancer-causing human papillomavirus types 16 and 18 in the bloodstream which highly correlates to antibody levels in the cervico-vaginal secretions. Furthermore, these antibodies to cancer-causing virus types 16 and 18 were detected and sustained for one year following completion of the vaccination course. These data were presented Tuesday at the AmericanCollegeof Obstetrics and Gynecology (ACOG) annual meeting.


“Cancer-causing human papillomavirus is very effective at hiding from the immune system because it exists within the cervical epithelium, away from the bloodstream,” said Prof. Dr. Tino F. Schwarz, Stiftung Juliusspital Wuerzburg, Germany, the lead study investigator. “This emphasizes the need for a cervical cancer vaccine to be effective in the cervix, at the site of infection. These data show there is a correlation between the vaccine inducing high antibody levels to the cancer-causing virus types in the bloodstream and the presence of antibodies in cervico-vaginal secretions, potentially providing antibodies where they are needed most.”


This study is a subset of data from 90 women participating in a larger, open, age-stratified trial of 666 women between 15 to 55 years of age. Blood samples were collected at several time points after the first vaccine dose, and cervico-vaginal secretions were collected at 18 months. Samples were measured for immune response against cancer-causing virus types 16 and 18. Results from the study show that antibodies to cancer-causing virus types 16 and 18 in the cervico-vaginal secretions were detected across all age groups.


The results also show that antibody levels in the bloodstream were in the same range as those seen in a separate efficacy study of females 15 to 25 years of age, which indicate that the GSK cervical cancer candidate vaccine has shown to provide in the trials a 100 percent efficacy for 5.5 years in preventing precancerous lesions due to cancer-causing virus types 16 and 18.


“These results are exciting, as they confirm that the higher the antibody levels in the blood, the higher the levels in the cervico-vaginal secretions, and present at the site of infection, where they are needed most,” said James Tursi, M.D., Director of Medical Affairs, North Americaat GlaxoSmithKline. “These data are critical in helping us to better understand how our cervical cancer candidate vaccine formulated with the novel adjuvant, AS04, helps provide protection against cancer-causing virus types.”


About Cervical Cancer
After breast cancer, cervical cancer is the leading cause of cancer-related death in women between the ages of 20 to 39 in the United States. The American Cancer Society estimates that in 2007 more than 11,000 women will be diagnosed with cervical cancer and nearly 4,000 will die from this disease in the United States. Furthermore, approximately 2 million precancerous lesions are diagnosed each year in the United States.


About The GSK Cervical Cancer Candidate Vaccine
GSK submitted aBiologics License Application for CERVARIX® with the U.S. Food and Drug Administration in March 2007. In addition, GSK has submitted a marketing authorization application to the European Medicines Agency, Australia, Canada, and numerous countries in Asiaand Latin America.


About GlaxoSmithKline
GlaxoSmithKline—one of the world’s leading research-based pharmaceutical and healthcare companies—is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, please visit www.gsk.com/media


GSK Biologicals (GSK Bio), one of the world’s leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline’s activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination pediatricvaccines which protect the world’s children with up to six diseases in one vaccine.

GlaxoSmithKline's investigational DTaP-IPV combination vaccine shown to be immunogenic and well-tolerated in Phase III clinical trial

GlaxoSmithKline (GSK) today announced results from a U.S. phase III vaccine clinical study presented this week at the Pediatric Academic Societies’ (PAS) Annual Meeting in Toronto, Canada. The study evaluated the immune response and safety profile of the investigational combination DTaP-IPV (diphtheria, tetanus, acellular pertussis - inactivated poliovirus) vaccine in children ages 4 to 6 years-old as compared to separately administered DTaP (INFANRIX®) and IPV (IPOL®) vaccines, when co-administered with measles, mumps and rubella (MMR) vaccine (M-M-RII®) at a separate site. Study results showed that children receiving the combination vaccine demonstrated overall a comparable immunogenicity and safety profile to children receiving the separately administered component vaccines.

The investigational DTaP-IPV vaccine has not been approved for use in the United States.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) recommend that children receive booster shots to protect against diphtheria, tetanus and pertussis (DTaP) and polio (IPV) at the 4 to 6 year-old doctor visit. Most states in the U.S. require either a fifth dose of DTaP vaccine and/or a fourth dose of IPV vaccine for kindergarten school entry. Separately administered DTaP and IPV vaccines are currently used to complete these recommended immunizations.

“An increasing number of vaccines are being recommended to prevent childhood diseases, including additional vaccines at the 4 to 6 year-old doctor’s visit,” said Barbara Howe, MD, Vice President, North American Vaccine Development, GlaxoSmithKline. “We are pleased to be developing a new combination vaccine that if approved, could offer one potential solution to the problem of increased number of injections during single doctor visits.”

DTaP-IPV Study Results
Study participants were distributed into two groups. The combination group (N=3,156 – consisting of three groups who received three different lots of DTaP-IPV pooled together) was made up of those children who received the DTaP-IPV plus MMR vaccines. The component group (N=1,053) was made up of those infants who received separately administered DTaP and IPV vaccines plus MMR vaccine. A subset of the children (N=1,331) had serological testing to evaluate the immunogenicity of DTaP-IPV vaccine.

Study results showed that children receiving the combination vaccine demonstrated overall a comparable immunogenicity and safety profile to children receiving the separately administered component vaccines. More specifically:
• Booster response was seen in at least 92.2 percent and 92.6 percent of children in the DTaP-IPV and INFANRIX plus IPOL groups, respectively, for each DTaP antigen.
• All subjects in both treatment groups had seroprotective levels of anti-D, anti-T, and anti-poliovirus types 2 and 3 antibodies; all but 1 subject (in the DTaP-IPV group) had seroprotective anti-poliovirus type 1 levels. At least 99.8 percent of subjects in both groups were seropositive for antibodies to pertussis agents.
• All pre-specified immunogenicity and safety non-inferiority criteria were achieved.
• Overall reported adverse events – including swelling at the DTaP-based injection site – were comparable in both study groups.


The most commonly reported solicited adverse event (AE) was pain at the DTaP-based injection site: reported by 57 percent of the children who received the investigational DTaP-IPV vaccine and 53 percent of the children who received the separately administered DTaP vaccine. This difference was statistically significant. Redness at the DTaP-based injection site was reported by 37 percent of the children who received the investigational DTaP-IPV vaccine and 37 percent of the children who received the separately administered DTaP vaccine; and swelling at the DTaP-based injection site was reported by 26 percent of the children who received the investigational DTaP-IPV vaccine and 27 percent of the children who received the separately administered DTaP vaccine.

The most commonly reported solicited general AE was drowsiness reported by 19 percent of the children who received the investigational DTaP-IPV vaccine and 18 percent of the children who received the separately administered DTaP and IPV vaccines. In addition, incidence of swelling with increased upper arm circumference at the DTaP-based injection site was 0.6 percent in the investigational DTaP-IPV vaccine group and one percent in the separately administered DTaP and IPV vaccines group.

GlaxoSmithKline: A Leader in Vaccines
GlaxoSmithKline, with U.S. operations in Philadelphia, PA, and Research Triangle Park, NC, is one of the world’s leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

GSK Biologicals (GSK Bio), one of the world’s leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline’s activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination pediatric vaccines which protect the world’s children, from up to six diseases in one vaccine.

Once daily, extended-release ropinirole improves Parkinson's symptoms in patients not optimally controlled with levodopa

Adding the once daily, investigational medication REQUIP® (ropinirole HCl) XL 24-Hour™ Extended-Release Tablets to Parkinson’s patients’ existing levodopa (L-dopa) therapy significantly reduced ‘off’ time, allowing patients to continue their daily activities for a longer period of time. ‘Off time’ describes the return of Parkinson’s symptoms as a patient’s medication wears off. The Ropinirole 24-Hour Prolonged Release Randomized, Controlled Study in Advanced Parkinson Disease (EASE-PD Adjunct Study) results, published in the April 3 issue of Neurology, show that adjunct treatment with REQUIP XL 24-Hour significantly reduced ‘off’ time by an average of more than two hours per day when compared to baseline prior to treatment.


“‘Off’ time is a common phenomenon for Parkinson’s patients. When symptoms like slowness of movement, tremor and rigidity return due to wearing off of the patient’s medication, it can be problematic, causing difficulty with simple activities and movement in patients with Parkinson’s disease,” said Rajesh Pahwa, M.D., Professor of Neurology, Director, Parkinson Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, Kan., and lead investigator of the EASE-PD Adjunct study. “These study results are significant, and show that with the investigational REQUIP XL 24-Hour added to L-dopa, patients can have more than two additional hours per day, on average, without experiencing the disabling symptom of ‘off ’ time.”


REQUIP® (ropinirole HCl) Tablets, the immediate-release (IR) formulation, is dosed three times daily. REQUIP XL 24-Hour has been designed to be given once daily and to have a simpler and faster titration schedule. In addition, it has been designed to provide a steady rate of absorption in the body to help reduce blood plasma fluctuations over 24 hours. In the EASE-PD Adjunct Study, REQUIP XL 24-Hour has been shown to be effective in treating both motor and non-motor symptoms of Parkinson’s disease as an addition to L-dopa. GlaxoSmithKline sponsored this study as part of the clinical development program for the investigational 24-hour extended-release tablet dosage formulation of REQUIP. REQUIP XL 24-Hour is the proposed brand name for a once-a-day formulation of ropinirole for treating Parkinson’s disease using SkyePharma Plc’s (Nasdaq: SKYE; LSE: SKP) proprietary GeoMatrix technology.

About the Study

The EASE-PD Adjunct study was a multi-center, double-blind, placebo-controlled study, conducted in patients with idiopathic Parkinson’s disease not adequately controlled with L-dopa. Subjects were randomized (1:1) to receive REQUIP XL 24-Hour (n=202) or placebo (n=191) in addition to L-dopa, once daily for 24 weeks. The primary endpoint was mean change from baseline in awake time spent ‘off’ (measured via patient diaries). REQUIP XL 24-Hour decreased patients’ awake time spent ‘off’ by an average of 2.1 hours per day, while placebo decreased awake time spent ‘off’ by 0.3 hours per day.


The study also included a wide variety of motor and non-motor secondary endpoints, including ‘on’ time which refers to the time during which medication is working and providing benefit, and ‘on’ time without troublesome dyskinesia which refers to ‘on’ time without involuntary movements interfering with function or causing discomfort, a common problem in Parkinson’s disease. REQUIP XL 24-Hour significantly increased both ‘on’ time and ‘on’ time without troublesome dyskinesia by 1.6 hours per day (a greater than 12 percent increase) and reduced the percentage of ‘off’ time by more than 12 percent compared to baseline. REQUIP XL 24-Hour also improved sleep problems associated with Parkinson’s disease, as measured by the Parkinson’s Disease Sleep Scale total score.


There were other motor and non-motor secondary endpoints in the study publication that were statistically significant. However, there were no significant differences between REQUIP XL 24-Hour compared to placebo in PDQ-39 subscales of social support, cognition or bodily discomfort. Additionally, there was no significant difference between REQUIP XL 24-Hour and placebo on the Epworth Sleepiness Scale total score signifying no increase in daytime sleepiness.


In the EASE-PD Adjunct study, once daily use of REQUIP XL 24-Hour was generally well tolerated. The withdrawal rate due to adverse events was low and similar between the two groups (REQUIP XL 24-Hour 5 percent versus placebo 5 percent). The most common adverse events reported in patients taking REQUIP XL 24-Hour (n=202) versus placebo (n=191) were dyskinesia (13 percent versus 3 percent), nausea (11 percent versus 4 percent), dizziness (8 percent versus 3 percent), somnolence (7 percent versus 4 percent), hallucinations (6 percent versus 1 percent), and orthostatic hypotension (5 percent versus 2 percent).

A Progressively Disabling Disease

Parkinson’s disease is a chronic, progressive and debilitating neurological condition that impairs the body’s ability to move and balance. Researchers have determined that Parkinson’s disease involves pathways in the brain responsible for motor control that are functioning improperly. Patients with Parkinson’s disease experience a reduction in dopamine, a key chemical in the brain that communicates messages about movement, resulting in the symptoms of Parkinson’s disease. These symptoms may include bradykinesia (slower-than-normal voluntary movements), rigidity (stiffness), tremor (involuntary shaking) and postural instability (trouble with balance).


More than one million people in the United Stateshave Parkinson’s disease, and it is estimated that nearly 60,000 new cases are diagnosed in the U.S.each year. Most people develop Parkinson’s disease between the ages of 40 and 70, but the disease can also develop at an earlier age.

About REQUIP Tablets (Immediate-Release Formulation)
The currently marketed REQUIP Tablets, a non-ergot dopamine agonist, has an indication in the U.S.for the treatment of the signs and symptoms of idiopathic Parkinson’s disease and is administered three times a day.


Prescription REQUIP is not for everyone. REQUIPTablets may cause patients to fall asleep or feel very sleepy during normal activities such as driving; or to faint or feel dizzy, nauseated, or sweaty when they stand up. Patients should tell their doctor if they experience these problems or if they drink alcohol or are taking other medicines that make them drowsy. Patients should also tell their doctor if they or their family notices that they develop any unusual impulses or behaviors, such as pathological gambling or hypersexuality. Hallucinations may occur at anytime during treatment. REQUIP may potentiate the side effects of L-dopa. Side effects include nausea, dizziness, drowsiness or sleepiness, headache, and dyskinesia (uncontrolled movements). Most patients were not bothered enough to stop taking REQUIP. This is not a complete list of side effects and should not take the place of discussions with patients’ healthcare providers. Their doctor or pharmacist can give patients a more complete list of side effects. Patients should talk to their doctor about any side effects they may have.


About SkyePharma PLC

SkyePharma develops pharmaceutical products benefiting from world-leading drug delivery technologies. The Company has nine approved products in the areas of oral, inhalation and topical delivery that are marketed throughout the world by leading pharmaceutical companies. For more information, visit www.skyepharma.com


About GlaxoSmithKline

GlaxoSmithKline, with U.S.operations in Philadelphia and Research Triangle Park, N.C., is one of the world's leading research-based pharmaceutical and health care companies.

FDA approves accelerated dosing schedule for GlaxoSmithKline's Twinrix

GlaxoSmithKline [NYSE:GSK] announced today that the U.S. Food and Drug Administration (FDA) has approved Twinrix® [Hepatitis A Vaccine (Inactivated) and Hepatitis B (Recombinant) Vaccine], for an accelerated dosing schedule that consists of three doses given within three weeks followed by a booster dose at 12 months. The approval means Twinrix, the only hepatitis A and hepatitis B combination vaccine available in the United States, is now available on a dosing schedule at 0, 7, 21-30 days, followed by a booster dose at 12 months. The vaccine was first approved for adults over age 18 years by the FDA in May 2001 on a 0, 1, 6-month dosing schedule.


“Hepatitis A and hepatitis B are serious liver diseases which can be prevented through vaccination,” stated travel medicine specialist Bradley A. Connor, M.D., Past President, International Society of Travel Medicine and a principal study investigator. “Twinrix’s new accelerated dosing schedule offers an option that could benefit individuals such as those preparing to travel internationally to high-risk areas. It may also benefit emergency first care responders, especially those deploying to disaster areas overseas, as well as others at risk for hepatitis, such as people with sexually transmitted diseases and those who are HIV positive.”


Many regions throughout the world are endemic for hepatitis A and hepatitis B, such as Africa, Asia, South Americaand parts of the Caribbean. Worldwide, approximately 1.5 million cases of hepatitis A are reported annually. In addition, hepatitis B has infected 2 billion people — one-third of the world’s population. Millions of Americans travel each year to countries where hepatitis A and hepatitis B are endemic. An overwhelming majority of these international travelers are not vaccinated before the trip. Therefore, international travelers may be at risk for contracting both hepatitis A and hepatitis B. They should consult their health care provider prior to traveling abroad.


The FDA approved the new dosing schedule after reviewing the safety and immune response of Twinrix given to 250 healthy adults (aged ≥18 years) at 0-, 7-, and 21- to 30-day schedule, followed by a booster dose at 12 months, compared to separate vaccinations with monovalent hepatitis A vaccine (HAVRIX at 0 and 12 months) and hepatitis B vaccine (ENGERIX-B at 0, 1, 2, and 12 months) given to 246 healthy adults as a control group. The study demonstrated that the individuals who completed the series of Twinrix on the accelerated dosing schedule had an immune response comparable to those individuals who received complete vaccination with separately administered hepatitis A and hepatitis B vaccines.


About Vaccine-Preventable Hepatitis (VPH)

Vaccine-Preventable Hepatitis includes hepatitis A and hepatitis B. Hepatitis C is not vaccine preventable. Hepatitis A is a serious liver disease caused by the hepatitis A virus. This virus is found in the stool of persons with hepatitis A and is spread by close personal contact and by eating food or drinking water contaminated with the hepatitis A virus. Hepatitis A can be easily passed between people within the same household. About one in five people with the disease has to be hospitalized. Hepatitis A can be fatal. Symptoms of the disease can include fever, fatigue, loss of appetite, nausea, abdominal discomfort, jaundice (yellow skin and eyes) and dark urine.


Hepatitis B is a serious liver disease caused by the hepatitis B virus. The virus is passed through infected blood or body fluids. Approximately 50 percent of people with hepatitis B do not notice signs or symptoms. Those who do may experience diarrhea and vomiting, nausea, fatigue, loss of appetite, muscle and joint pain, and jaundice. Hepatitis B can cause lifelong infection, cirrhosis (scarring) of the liver, liver cancer, liver failure, and death. An estimated 1.25 million Americans are chronically infected with Hepatitis B. Estimates show that tens of thousands of people (mostly young adults) are infected each year.


About Twinrix®

As with all prescription medications, please talk with your healthcare provider to see if Twinrix is right for you.


In clinical trials with Twinrix, the most common side effects included pain and redness at the injection site, headache, and tiredness. These effects were mild and did not last more than 48 hours. (See Adverse Reactions section of the Prescribing Information for Twinrix for other potential side effects.) As with any vaccine, there is a small risk of allergic reactions. If you notice any problems following vaccination, or if you are allergic to any component of the vaccine such as neomycin, yeast, or latex, please inform your healthcare provider.


For more information on Twinrix visit www.gskvaccines.com


GlaxoSmithKline — A Leader in Vaccines

GlaxoSmithKline — one of the world’s leading research-based pharmaceutical and healthcare companies — is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline at www.gsk.com

GlaxoSmithKline K.K. seeks approval in Japan for lapatinib, a new treatment for breast cancer

GlaxoSmithKline K.K. (Head Office: Shibuya-ku, Tokyo, President: Marc Dunoyer, hereinafter referred to as GSK) announced the submission of a New Drug Application (NDA) to the Japanese authorities for approval to market lapatinib, its new cancer drug on 30 March. The indication for which the company seeks approval is for both monotherapy and for combination treatment with capecitabine* for patients with advanced or metastatic HER2 positive breast cancer in women who have received prior therapy including an anthracycline, a taxane, and trastuzumab.


In the US, lapatinib was approved on 13 March in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.Lapatinib is now marketed as Tykerb in the US. Marketing applications for lapatinib have been filed around the world, including the European Union, Switzerland, Canada, Brazil, Australia, and South Korea.


Lapatinib, a small molecule that is administered orally, inhibits the tyrosine kinase components of the EGFR (ErbB1) and HER2 (ErbB2) receptors. Stimulation of EGFR (ErbB1) and HER2 (ErbB2) is associated with cell proliferation and with multiple processes involved in tumor progression, invasion, and metastases. Overexpression of these receptors has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival.


GlaxoSmithKline - one of the world’s leading research-based pharmaceutical and healthcare companies- is committed to improving the quality of human life by enabling people to do more, feel better and live longer.



*In Japan, capecitabine is marketed as Xeloda® by Chugain Pharmaceutical Co., LTD

GlaxoSmithKline files meningococcal conjugate vaccine

GlaxoSmithKline announced today the submission of a regulatory file to European Medicines Agency (EMEA) under Article 58 for the combination vaccine candidate Globorix™ (diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Neisseria meningitides serogroups A and C). In clinical trials including countries in Africaand Asia, the conjugate meningococcal vaccine has demonstrated a good safety profile and immunogenicity against meningococcal meningitis caused by Neisseria meningitidis serogroups A and C in addition to five other major childhood diseases. Under Article 58, the EMEA, in cooperation with the World Health Organization (WHO), gives a scientific opinion on the efficacy, quality and safety of medicinal products intended for use exclusively outside the European Union.


“GSK’s long-standing commitment to the developing world is reflected in the development of Globorix™, a vaccine designed specifically to meeta pressing public health threat in Africa,” said Jean Stéphenne, President of GlaxoSmithKline Biologicals. “Using the innovative Article 58 mechanism will expedite the availability of Globorix™ to those in greatest need while ensuring it meets the world’s most stringent standards for safety and efficacy. This vaccine candidate could be available as early as 2008 and has the potential to break the cycle of meningitis epidemics in Africa. It will provide babies with protection against 7 diseases in a combination vaccine and, administered in the classical Expanded Programme on Immunisation, it will help to simplify logistics and costs.”


In 2000 the WHO and leading public health experts called for the development of conjugate vaccines in order to shift meningitis control away from expensive last-minute outbreak immunization campaigns towards a more sustainable and long-term prevention strategy. Until today no combined conjugate meningococcal vaccine has been available to protect infants in Africaagainst the disease.


The current meningitis control strategy relies on reactive mass immunization campaigns using polysaccharide vaccines. While these campaigns are estimated to have saved 70% of lives in epidemics, this older type of vaccine has significant drawbacks. Polysaccharide vaccines do not offer protection to infants and in older children and adults they only protect for 3-5 years, leaving them vulnerable to future epidemics. Polysaccharide vaccines also do not address endemic meningitis1.


“There is an urgent need for an improved meningococcal vaccine,” said Dr. A. Hodgson, Director, Navrongo Health Research Center, Ghana. “Children are at great risk during the first two years of life and currently we are powerless to protect them with the polysaccharide vaccines. The filing of this new vaccine is good news for African infants because it means that state of the art vaccine technology is now one step closer to those who need it,” continued Dr. Hodgson. “The arrival of Globorix™and other new conjugate vaccines is the start of a new era in meningococcal disease control for Africa.”


Meningococcal meningitis is a highly contagious infection caused by the bacterium Neisseria meningitidis. The bacteria are transmitted through respiratory secretions, such as sneezing or coughing, and direct contact with infected people. Without treatment, the mortality rate can go up to 50%2, with most deaths occurring only 24-48 hours after the appearance of symptoms. Africa’s “meningitis belt” encompasses 21 countries in sub-Saharan Africa and is home to more than 400 million people. Endemic meningitis infects children year-round and large outbreaks routinely occur during the dry season – between December and June – and major epidemics occur in cycles, every 8 – 12 years. The largest recorded outbreak took place in 1996 when 250,000 people contracted the disease and 25,000 died2.


Globorix™is intended for use in African meningitis belt countries, the Middle-East and Northern Africa, where it could replace the pentavalent combination vaccine (diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b) already administered to many children. The new vaccine has been designed to fit with the Expanded Programme on Immunisation (EPI) calendar of organized infant immunization campaigns in Africa, which makes it an attractive and relevant public health response to a devastating disease in Africa.


GlaxoSmithKline Biologicals
GlaxoSmithKline Biologicals (GSK Biologicals) is one of the world’s leading vaccine manufacturers. The company is located in Rixensart (Belgium) and is the centre of all GlaxoSmithKline’s activities in the field of vaccine research, development and production. GSK Biologicals employs over 5 000 people in Belgium (over 8 000 worldwide), of whom more than 1 500 are passionate scientists devoted to discovering innovative vaccines and developing cost-effective and convenient combination products that contribute to the health and well-being of billions of people, in every generation around the world.


In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination paediatric vaccines which protect the world's children up to six diseases in one vaccine.


GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and health care companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com


References

1. Bull World Health Organisation, Vol. 81, No. 10, Genebra Oct. 2003
2. WHO, Weekly epidemiological record, No. 37, 2005, 80, 313-320

Merck & Co., Inc. and Lundbeck Discontinue Joint Development Program for Gaboxadol, an Investigational Compound for Insomnia

Merck & Co., Inc., and H. Lundbeck A/S announced today the discontinuation of their joint development program for gaboxadol, an investigational new medicine for the treatment of insomnia currently in Phase III development. Data from recently completed clinical studies suggest that the overall clinical profile for gaboxadol in insomnia does not support further development.

As a result of this new information, Merck and Lundbeck will not file a new drug application for gaboxadol for the treatment of insomnia with the U.S. Food and Drug Administration (FDA), or other regulatory agencies worldwide, and are terminating ongoing clinical studies.

"The termination of our joint insomnia development program with Lundbeck is clearly disappointing," said Dr. Peter S. Kim, president of Merck Research Laboratories. "Lundbeck has been a valued partner for the past three years, and our collaboration has benefited from the strong relationship between the companies. Although Merck will not be continuing with the clinical development program for gaboxadol for the treatment of insomnia, we remain committed to our neuroscience and sleep disorders research program, one of nine priority disease areas for research and product development. As part of that commitment, we also welcome the opportunity to engage in other joint development efforts with Lundbeck in the future."

"When developing new and innovative medicines there are always risks of failure, particularly for broad-based therapeutics which often carry a higher threshold for demonstrating value to physicians, and ultimately to patients," said senior vice president Anders Gersel Pedersen, head of development at Lundbeck. "It is clearly disappointing, but we will continue to develop new and innovative medicines to treat unmet medical needs and to seek strong and productive partnerships like the one we have experienced with Merck to maximize these efforts."

About Merck & Co., Inc.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com

About Lundbeck
H. Lundbeck A/S is an international pharmaceutical company engaged in the research and development, production, marketing and sale of drugs for the treatment of psychiatric and neurological disorders. In 2006, the company's revenue was DKK 9.2 billion (approximately EUR 1.2 billion or USD 1.6 billion). The number of employees is approximately 5,300 globally. For further information, please visit www.lundbeck.com

Calcium channel blocker Adalat GITS offer additional benefits

Two recently published articles in the Journal of Clinical Epidemiology provide further evidence that the use of the long-acting calcium channel blocker (CCB) nifedipine GITS (Adalat GITS) has additional benefits beyond its blood pressure lowing effect. A first publication from Lubsen et al. (Journal of Clinical Epidemiology 2007; first published online) demonstrates that while the blood pressure lowering effect of nifedipine GITS did play a major role in the reduction of debilitating stroke and new overt heart failure, the anti-anginal and vascular protective effects of nifedipine GITS seem to be just as important in reducing cardiovascular events.

A second publication by Poole-Wilson et al. (Journal of Clinical Epidemiology 2007; first published online) also demonstrates that a nifedipine GITS therapy in patients with stable angina can help contain healthcare expenses by reducing the need for additional medication and the use of expensive diagnostic and surgical procedures. Both these papers are based on analyses of the ACTION-database. ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) collected data from 7,665 patients with stable angina pectoris.

Lowering blood pressure helps reduce stroke and heart failure
The ACTION-trial showed that adding nifedipine GITS to a best practice angina pectoris therapy significantly reduced the incidence of any stroke or TIA (28%) and the development of new overt heart failure (29%). Using an innovative statistical approach, Lubsen et al. found that nifedipine GITS’ ability to lower systolic blood pressure was largely responsible for these impressive results. The reduction in the risks of coronary angiography and surgery, attributed to nifedipine GITS on the other hand, are likely to be due to an anti-anginal and a vascular protective effect.


Efficient utilization of resources
Using the ACTION data, Poole-Wilson et al. showed that adding nifedipine GITS to the best practice therapy reduced the need for additional medication and also the use of expensive diagnostic and surgical procedures together with their associated costs. Basis for the calculation of hospital expenses was a reference hospital in the Netherlands. The estimated cost of medication was also based on drug pricing in the Netherlands. In total the incremental cost of the nifedipine GITS therapy was just about € 69 per year, or about € 3,036 per year of event free survival.


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 business operates under the name Bayer Schering Pharma AG, Germany. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide.

Bayer Schering Pharma
Bayer Schering Pharma AG, Germany, is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized Therapeutics and Women's Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life.

Per Peterson, M.D., Ph.D., Joins Board of Directors of Invitrogen Corporation

Invitrogen Corporation (Nasdaq:IVGN) today announced that Per Peterson, M.D., Ph.D. has been appointed to its board of directors, effective March 1, 2007. Dr. Peterson recently retired as Chairman, Research & Development, at Johnson & Johnson. As Chairman, he had responsibility for the Corporate Office of Science and Technology, the Enterprise-wide R&D Council, and Johnson & Johnson's cell therapy research activities. Dr. Peterson was also a member of the Executive Committee of Johnson & Johnson.

"We are very pleased to be adding someone of Dr. Peterson's reputation and experience to our board," said Greg Lucier, Invitrogen's Chairman and Chief Executive Officer. "As a leader in the life sciences, we are focused on creating technologies that accelerate biological understanding. In his role as director, Dr. Peterson will provide invaluable insight, advice and guidance to ensure Invitrogen remains on the cutting edge of innovation that makes a difference to researchers."

Dr. Peterson joined Johnson & Johnson in 1994 as Vice President, Drug Discovery, of the R.W. Johnson Pharmaceutical Research Institute. He was named Group Vice President of the Pharmaceutical Research Institute in April 1998 and its President in November 1998. In 2000, Dr. Peterson was named Chairman, Research & Development, Pharmaceuticals Group. Dr. Peterson became a Member of the Executive Committee in 2001.

Prior to joining Johnson & Johnson, Dr. Peterson spent eight years at Scripps Research Institute in La Jolla, CA, where he headed the Division of Molecular Immunogenetics before being appointed Chairman of the Department of Immunology in 1987. He had earlier served as Director of the Wallenberg Laboratory, as well as professor of cell biology at the University of Uppsala, Sweden.

Born in Kalmar, Sweden, Dr. Peterson received his B.M. in Medicine and his Ph.D. in Medicinal Biochemistry from the University of Uppsala, Sweden.

About Invitrogen

Invitrogen Corporation (Nasdaq:IVGN) provides products and services that support academic and government research institutions and pharmaceutical and biotech companies worldwide in their efforts to improve the human condition. The company provides essential life science technologies for disease research, drug discovery, and commercial bioproduction. Invitrogen's own research and development efforts are focused on breakthrough innovation in all major areas of biological discovery including functional genomics, proteomics, bioinformatics and cell biology -- placing Invitrogen's products in nearly every major laboratory in the world. Founded in 1987, Invitrogen is headquartered in Carlsbad, California, and conducts business in more than 70 countries around the world. The company is celebrating 20 years of accelerating scientific discovery. Invitrogen globally employs approximately 5,000 scientists and other professionals and had revenues of more than $1.26 billion in 2006. For more information, visit www.invitrogen.com

GSK initiates first global Phase III study of Tykerb (lapatinib) in head and neck cancer

GlaxoSmithKline today announced the start of an international Phase III trial of its investigational cancer treatment Tykerb® (lapatinib) in squamous cell carcinoma of the head and neck (SCCHN). This announcement follows the International Meeting on Innovative Approaches in Head & Neck Oncology, Barcelona, Spain, 22nd-24th February supported by the European Society for Therapeutic Radiology and Oncology (ESTRO), where GSK presented results from a Phase I study of lapatinib in SCCHN.


This large adjuvant trial will compare the effectiveness of oral lapatinib versus placebo given in high-risk patients following surgery. SCCHN is the sixth most common cancer worldwide[1]: 600,000 people are diagnosed with SCCHN annually1, 100,800 in Europe alone and 40,000 people die from the disease every year.[2]


The design of this Phase III trial was based on recent results from two large-scale, independent randomized studies that demonstrated the new standard of care in the post-operative treatment of high-risk SCCHN patients with additional use of chemotherapy.[3],[4] However, research suggests that approximately one quarter to one third of advanced head and neck cancers that are primarily treated with surgery and radiation therapy come back following treatment.3,4


“The initiation of this trial represents another exciting step towards understanding the role of lapatinib in other tumour types beyond breast cancer,” says Professor Jean Bourhis, Head of Radiation-Oncology Department, Institute Gustave Roussy, France and principal investigator for this trial. “There is a significant group of patients who are at high-risk of disease recurrence following surgery, and they need new treatments that can be combined with standard chemoradiation therapy.”


This global, Phase III study will enroll 680 high-risk patients with locally advanced head and neck cancer (stages II, III and IVa) that have undergone surgery. Patients will receive, within four to seven weeks after surgery, either lapatinib (1500 mg) or placebo tablets once-daily with radiotherapy and cisplatin for seven weeks. After this time, patients will continue with either lapatinib or placebo treatment for one year. The principal objective will be to investigate the length of time without disease symptoms, and overall survival with other clinical factors will also be measured. Side effects will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).


Results from a Phase I dose-escalation study of lapatinib (doses ranged from 500 mg to 1500 mg) plus chemoradiation in 31 head and neck cancer patients were presented at the conference. Results identified 1500 mg of lapatinib taken once-daily with chemotherapy and radiotherapy as the optimal dose for this combination, and this dose was selected for the Phase III study. Additionally, 89% of patients had a tumour response to this combination treatment. The most common side effects in the Phase I study were mouth ulcers (87%), radiation skin injury (65%), nausea (61%), swallowing difficulties (52%) and vomiting (52%).[5]


“Having already shown promise as a breast cancer treatment, we are very excited to continue investigating lapatinib in SCCHN,” said Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Centre, GSK. “Lapatinib may represent a new treatment approach to difficult-to-treat tumour types, such as head and neck cancer, offering hope to patients in need of a further treatment option.”


Lapatinib blocks the activation of two key receptors, EGFR (ErbB1) and HER2 (ErbB2), associated with increased growth and development of this type of head and neck tumour. Stimulation of these receptors is associated with multiple processes involved in tumour growth. An excessive presence of these receptors has been reported in a variety of human tumours and is associated with poor outcome and reduced survival.


About SCCHN

SCCHN is the most common form of cancer of the head and neck, and approximately two-thirds of all patients are diagnosed with advanced disease. EGFR and HER2 are two types of receptors found on tumours which play a key role in the development of this type of head and neck cancer. Researchers have found that the excessive expression of EGFR receptors is nearly universal in SCCHN disease, with large numbers of HER2 receptors present in 20 to 40 percent of tumours.[6],[7]


About Lapatinib

Lapatinib was discovered and developed by GSK as an oral once daily therapy, and is currently being investigated in breast cancer and other solid tumours. Lapatinib has proven efficacy in advanced breast cancer. Phase III results of lapatinib plus capecitabine show superior efficacy to capecitabine alone in women with HER2 positive advanced breast cancer who have progressed following prior therapy, including trastuzumab.[8]

The most frequent side-effects related to lapatinib from clinical trials to date are mild to moderate (grade 1 or 2) diarrhoea, nausea, vomiting, fatigue and rash.[9]

GSK is using advanced technologies, including pharmacogenomics, to better define patient populations that may respond to lapatinib.

Lapatinib is an investigational drug that is not yet approved for marketing by any regulatory body.

Lapatinib in combination with capecitabine has been submitted for marketing approval in the United States, European Union and Switzerlandfor the treatment of advanced or metastatic HER2 positive breast cancer in women who have progressed despite prior therapy, including trastuzumab. Registration dossiers have also been filed in Australia, Canadaand New Zealand.


GSK in Oncology

GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s “bench to bedside” approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes partnerships with more than 160 cancer centres. GSK is developing a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.



References:
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[1] Study EGF102988 protocol

[2] Mouth Cancer Foundation. Initiative of the Restorative Dentistry Oncology Clinic: http://www.rdoc.org.uk/ accessed 3rd Jan 2007

[3] Bernier J, Domenge C et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. NEJM; 2004 May 6;350(19):1945-52

[4] Cooper J, Pajak TF et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. NEJM; 2004 May 6;350(19):1937-44.

[5] El-Hariry, I., Harrington K. et al. A phase I, open label study (EGF100262) of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Oral presentation, 1st International Meeting on Innovative Approaches in Head & Neck Oncology, Barcelona, Spain. 22nd - 24th February 2007.

[6] Khademi B, Shirazi FM, Vasei M, et al. The expression of p53, cerbB-1 and cerbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors. Cancer Letters 2002;184:223-230.

[7] O-Charoenrat P, Modjtahedi H, Rhys-Evans P et al. Epidermal Growth Factor-like Ligands Differentially Up-Regulate Matrix Metalloproteinase 9 in Head and Neck Squamous Carcinoma Cells.Cancer Research,2000; 60:1121-1128.

[8] Geyer C, Forster J, Lindquist D, Chan S, Romieu C et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N EnglJ Med 2006; 355;2733-43.

[9] GSK data on file. Ongoing studies to 15 November 2005