A New Emergency Contraceptive Plan B® One-Step Received Final FDA Approval

Gedeon Richter Plc. confirmed that a new emergency contraceptive Plan B® One-Step (1.5 mg levonorgestrel 1x), developed and manufactured in finished dosage form by Gedeon Richter Plc. in partnership with Teva Pharmaceutical Industries Ltd., received final U.S. Food and Drug Administration approval.

Plan B^® One-Step provides an innovative way of preventing unintended pregnancy with one tablet in one dose.

Teva has the exclusive rights to market and distribute the product in North-America.

Richter’s 1.5 mg levonorgestrel containing emergency contraceptive product has been already launched in several markets including Hungary, CIS republics and many of the European Union member states.

Gedeon Richter Plc. manufactures and markets a wide range of Women’s Healthcare products and is widely considered to be one of the leading companies in this therapeutic field. Richter has pioneered the development and introduction of emergency contraceptive products world-wide based on its focused strategy and expertise in steroid chemistry.

Plan B^® One-Step is a registered trademark of Women’s Capital Corporation, a subsidiary of Duramed Pharmaceuticals, Inc.

Novartis Arthritis Trial Gets Good Results

New Phase II data show ACZ885 gave better pain relief and flare prevention for patients with chronic gout than an injectable corticosteroid

• ACZ885 provided pain relief and reduced risk of flares by 94% versus an injectable corticosteroid in hard-to-treat patients unable to use common gout medicines

• Gout is one of the most painful forms of arthritis involving acute attacks of inflammation that can damage joints and bone

• ACZ885 blocks action of inflammatory protein interleukin-1 beta which plays key role in causing painful gout flares

New Phase II results show that the novel biological therapy ACZ885 (canakinumab) is significantly more effective than an injectable corticosteroid at reducing pain and preventing recurrent attacks or 'flares' in patients with hard-to-treat gout, one of the most painful forms of arthritis.

The study met its primary endpoint by showing that during acute gout flares, ACZ885 reduced pain faster and more effectively than the injectable corticosteroid triamcinolone acetonide, a potent steroid with sustained effect used to treat severe inflammatory conditions (p<0.05).

At the end of the eight-week study, the risk of flare recurrence was 94% less for patients on ACZ885 than on the steroid (p=0.006). The results were presented today at the American College of Rheumatology (ACR) Annual Scientific Meeting in Philadelphia, USA.

"If not appropriately treated, gout can be a devastating condition. Current therapies can have limited efficacy and tolerability, and may be unsuitable for some patients," said Professor Alexander So, MD, Department of Rheumatology at the University of Lausanne, Switzerland.

"These results are important as they indicate that canakinumab may provide significant benefit in both the prevention and treatment of painful acute flares in these hard-to-treat patients."

ACZ885 is a fully human monoclonal antibody which blocks the action of the inflammatory protein interleukin-1 beta (IL-1 beta). It has already been approved under the brand name Ilaris® in a number of countries for treating cryopyrin-associated periodic syndrome (CAPS), a rare life-long auto-inflammatory disease with debilitating symptoms and few treatment options.

Studies with ACZ885 are ongoing in other diseases in which IL-1 beta plays an important role, such as chronic obstructive pulmonary disease (COPD), type 2 diabetes and systemic juvenile idiopathic arthritis (SJIA). Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.

Gout, also known as gouty arthritis, affects more than 1% of adults in Western countries. It is more common in older people, with around 10% of men and 6% of women over 70 years old suffering from the disease. Approximately one in 10 patients have poorly controlled gout resulting in more frequent flares. They are regarded as being 'hard-to-treat' as they are often intolerant or unresponsive to standard medications such as colchicine or non-steroidal anti-inflammatory drugs (NSAIDs). Corticosteroids have traditionally been given to these patients as a last resort to treat acute pain, but they may have significant side effects.

Gout is caused by the accumulation of uric acid crystals leading to severe inflammation in the joints and surrounding tissue. Recent advances in the understanding of the disease have shown that uric acid crystals activate production of IL-1 beta, which is responsible for the inflammatory symptoms experienced by gout patients. ACZ885 provides a potent and selective blockade of IL-1 beta for a sustained period, neutralizing it and reducing inflammation.

"The devastating impact of chronic gout is often underestimated by both healthcare professionals and the general public, and there is a real unmet need among patients," said Trevor Mundel, MD, Head of Global Development at Novartis Pharma AG. "The latest data are encouraging for patients with hard-to-treat gout in whom the disease is not effectively managed, resulting in chronic pain. These findings also reinforce the potential of ACZ885 in a number of inflammatory diseases where IL-1 beta plays a key role."

The results presented at ACR were from a randomized, single-blind, double-dummy Phase II study involving 200 patients aged 18-80 years old with chronic gout, designed to assess the efficacy and optimum dose of ACZ885 in patients for whom current treatments (colchicine and/or NSAIDs) are ineffective or contraindicated.

The study showed that patients given ACZ885 150 mg experienced faster and more effective pain relief than those given the corticosteroid triamcinolone acetonide from 24 hours up to seven days. ACZ885 was given by subcutaneous injection, i.e. under the skin, whereas the steroid was given by intramuscular injection, i.e. into the muscle.

No pattern of adverse events was seen in any of the treatment groups and the incidence of adverse events was similar for both medicines. Serious adverse events occurred in two patients receiving ACZ885 and one receiving triamcinolone acetonide. Investigators reported that these events were not related to the study drug. There were no discontinuations due to adverse events.

Ilaris has been launched in the US and Switzerland, and received a positive opinion recommending approval in the EU in July 2009 to treat adults and children over four years old with CAPS. In the US, Ilaris is approved to treat adults and children four years of age and older with CAPS, including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). Reviews are ongoing in other countries including priority review in Australia, Brazil and Canada. Ilaris has been designated as an orphan drug for treating SJIA in the US, EU and Switzerland, and has fast-track status for SJIA in the US.

Bayer’s novel oral contraceptive Qlaira® significantly reduces heavy menstrual bleeding

Results also confirm significant improvement in blood iron levels

Qlaira®, the novel oral contraceptive containing estradiol valerate/dienogest significantly reduced menstrual blood loss (MBL) in a clinical study with women suffering from heavy and/or prolonged menstrual bleeding without organic pathology. The results of this international trial were presented today by Ian Fraser, M.D., the principal investigator, at the World Congress of the International Federation of Gynecology and Obstetrics (FIGO). Qlaira® also improved iron metabolism parameters in these women. Abnormal uterine bleeding is a very common symptom among women of reproductive age.

“The excellent data from our Phase III study with Qlaira® clearly underscore that our new oral contraceptive could offer a new treatment option for many women who suffer from this common disorder”, said Phil Smits, M.D., Head of Women’s Healthcare at Bayer Schering Pharma.

In a double-blinded, randomized, placebo-controlled trial with 231 women in Europe and Australia Qlaira® was compared to a placebo. Study participants were confirmed to have heavy and/or prolonged menstrual bleeding over a 90-day run-in period before they were randomized into the Qlaira® or placebo treatment group. During the 90-day-treatment period, MBL was reduced by 458 ml in the Qlaira® group and by 93 ml in the placebo group.

A significant improvement in iron metabolism parameters was only observed in the Qlaira® group; the adjusted mean difference in haemoglobin and ferritin concentrations with Qlaira® vs. placebo was +0.6g/dL.

Data from a second Phase III study with the same study design, conducted in parallel in the USA and Canada, will be presented at the 65th Annual Meeting of the American Society for Reproductive Medicine (ASRM) in Atlanta on October 17-21, 2009.

Bayer submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for this new estradiol-based oral contraceptive (estradiol valerate/dienogest) in July 2009. It is seeking approval for two indications: oral contraception and the treatment of heavy and/or prolonged menstrual bleeding in women without organic pathology who desire oral contraception. Bayer is planning to seek approval for the indication heavy and/or prolonged menstrual bleeding in women without organic pathology who desire oral contraception in Europe in 2010. This new oral contraceptive has been available in several European countries since May 2009 under the tradename Qlaira® for the indication oral contraception.

About the Phase III-study
The 231 study participants of the multicenter-study in Europe and Australia were aged >18 years. The participating women underwent a 90-day run-in phase to confirm the diagnosis of prolonged bleeding (two bleeding episodes, each lasting more than eight days), frequent bleeding (more than five episodes with more than 20 bleeding days overall), or heavy bleeding (more than two episodes each with a blood loss volume of more than 80 ml). Mean MBL during this run-in-period was 639 – 645 ml in total. Normal blood loss per monthly cycle is approximately 80 ml.

Following the run-in-phase the study participants were randomized to Qlaira® (n=149) or the placebo (n=82) for treatment over 196 days ( 7 treatment cycles). Data from the last 90 days of treatment and the 90-day run-in period was compared. Women who received Qlaira® as a study medication lost on average (adjusted mean difference) 373 ml less blood over the 90-day.

This new product with an estradiol valerate/dienogest combination is the first in a new class of oral contraceptives to deliver estradiol, the estrogen identical to the one produced by the female body. It has a unique dosing regimen which has been designed to deliver hormones at the right levels at the right time during the cycle.

About heavy and/or prolonged menstrual bleeding
Heavy and/or prolonged menstrual bleeding is defined as abnormal uterine bleeding in the absence of organic pathology or medical illness (e.g. fibroid, endometriosis).

Prevalence studies indicate that abnormal uterine bleeding is a very common symptom suffered by women of reproductive age. In the US, menstrual disorders affect nearly 2.5 million women annually and are the most prevalent gynecological condition.

Studies assessing the prevalence of heavy bleeding (blood loss of 80 ml or more per menstrual period) using the objective measurement of blood loss report a worldwide prevalence range of between 9% and 14%. Objective measurement only captures one of the symptoms suffered by women with abnormal uterine bleedings (AUB), whereas subjective or self-reported measurement considers the overall impact on quality of life and is therefore likely to result in higher prevalence rates.

Bayer Schering Pharma Collaborates With AC Immune in The Field of Alzheimer´s Disease

Florbetaben will be used for the very first time in Alzheimer´s patients being treated with a vaccination therapy.

Bayer Schering Pharma AG, Germany, will provide its development candidate florbetaben, a so called PET (positron emission tomography) tracer, to the Swiss-based biopharmaceutical company AC Immune SA, to support a clinical trial in the field of Alzheimer´s disease (AD). This study is conducted to develop a therapy option for the treatment of AD. Bayer´s novel PET tracer florbetaben will be applied for imaging of beta-Amyloid deposition in the brain of patients undergoing the phase I clinical testing of AC Immune´s Alzheimer´s vaccine ACI-24. In this collaboration, florbetaben will be tested for the very first time in the development of a potential therapeutic for Alzheimer’s patients.

“Bayer Schering Pharma has already demonstrated the potential of florbetaben to image beta-Amyloid deposition in the brain in its own phase II study,” said Dr. Thomas Balzer, Head of Global Clinical Development Therapeutic Area Diagnostic Imaging at Bayer Schering Pharma. “The cooperation with AC Immune enables the collection of valuable clinical data for florbetaben in patients treated with AC Immune’s novel therapeutic vaccine.”

”This collaboration with Bayer Schering Pharma adds further value to our Alzheimer´s vaccine ACI-24,” said Prof. Andrea Pfeifer, CEO of AC Immune. “The adoption of a diagnostic imaging substance visualizing the deposition of beta-Amyloid that is targeted by our vaccine can be an important parameter for dose selection, and will provide useful complementary data. There is a key trend in the industry to co-develop therapy guiding diagnostics alongside drugs for patients. We look forward to working with Bayer´s experts in this ground-breaking collaboration.”

Currently, there is no diagnostic test on the market that can detect beta-Amyloid deposition in the brain – a pathological hallmark of Alzheimer´s disease – in patient´s lifetime. Today, the clinical diagnosis of AD is based on cognitive tests, Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) scans to exclude other dementia diseases. Unfortunately, clinical diagnosis is often made too late and does not always correlate with post-mortem diagnosis. A good diagnostic assay should also help to better evaluate the effect of new treatments in clinical trials as well as correlate better with existing pathological and memory markers. A new diagnostic tool to detect beta-Amyloid in the brain in vivo might also be beneficial in detecting the disease earlier, before the symptoms are too advanced so treatment could be started earlier.

About Florbetaben (18 F)
Florbetaben is an inlicensed 18F-labeled PET tracer that specifically binds to deposition of beta-Amyloid. These depositions (plaques) consist of proteins that accumulate in the brain and are a pathological hallmark of Alzheimer’s disease. As the aggregation of the beta-Amyloid protein in the brain is also a key target for new therapeutic treatments under development, florbetaben might also be able to support the development of these new treatment approaches. A phase II study showed that patients with clinical diagnosis of Alzheimer´s disease could be differentiated from age-matched healthy volunteers on the basis of florbetaben uptake pattern in the brain. The results of this study were presented at the International Conference on Alzheimer’s diseases (ICAD) in Vienna, Austria in July 2009.
Find more information at www.viva.vita.bayerhealthcare.com

About ACI-24
ACI-24 is an active vaccine stimulating the patient's immune system to produce beta-sheet conformation-specific antibodies that prevent plaque deposition or enhance its clearance. During preclinical development, the ACI-24 has shown high efficacy in vivo by memory restoration and plaque reduction. The vaccine is also characterized by a very high specificity due to generating a conformation-specific antibody response. The favourable safety profile of ACI-24 is underlined through the absence of local inflammation in relevant models as well as its T-cell independent mechanism shown in preclinical development.

About the ACI-24 clinical trial
It is a phase I, randomized, double blind, placebo controlled clinical study with the primary objective of evaluating the safety and tolerability of ACI-24 and a secondary objective of evaluating efficacy (immune response and clinical assessment) in mild to moderate AD patients. Phase I is designed to allow for the identification of the best dose of vaccine to be used further in phase II. Three groups of patients, each receiving a different dose of ACI-24, will be observed.

About Alzheimer’s Disease
Alzheimer’s disease is a devastating neuro-degenerative disease and the most common cause of dementia. Most cases of Alzheimer’s disease affect people over the age of 60. It is a progressive disease that can lead to premature death. In 2006, estimates suggested that more than 26 million people worldwide were suffering from Alzheimer’s disease. By 2050, this number could reach more than 100 million. At present there is no cure for Alzheimer’s disease, but treatments for symptoms, combined with the right services and support, can make life better for the millions of people living with Alzheimer’s.

Actavis’ Clients Launch First Generic Atorvastatin in Spain

Actavis announced that its third-party sales division, Medis, has delivered 30 million tablets of Atorvastatin to its clients in Spain. This is the first generic version of the blockbuster molecule to reach the Spanish market.

The product, Atorvastatin Magnesium, is launched by four of Spain’s largest generic pharmaceutical companies. Distribution of the product to Spanish pharmacies has already commenced.

Atorvastatin efficiently regulates the blood cholesterol levels and is one of the most effective drugs used in the therapy of primary hypercholesterolemia. Atorvastatin Magnesium is produced by Actavis in 10mg, 20mg and 40mg tablets. Pfizer, the originator, markets its product in Spain under the brand names of Cardyl® and Zarator®. Atorvastatin’s US brand name is Lipitor®.

Atorvastatin tablets are subject to widely varying patent situations around the world, which is why Medis has invested significantly in different forms of the molecule. In Spain, the patent landscape is different to other Western European markets, and the originator product, containing Atorvastatin Calcium, is patented until 2010.

Medis is currently promoting three different dossiers for Atorvastatin and has been supplying a product suitable for Central Eastern Europe for close to two years. Medis’ alternative generic, Atorvastatin Magnesium, can be launched in Spain now, as it has been approved by the Spanish authorities.

FDA approves GlaxoSmithKline’s Votrient™ for advanced renal cell cancer

GlaxoSmithKline [NYSE: GSK] announced that the U.S. Food and Drug Administration (FDA) has approved Votrient™ (pazopanib) to treat patients with advanced renal cell carcinoma (RCC), a form of kidney cancer. Approximately 57,700 people in the U.S. will be diagnosed with kidney cancer this year, and 13,000 people will die from this disease.

“RCC is the most common malignancy of the kidney and is highly resistant to chemotherapy,” said Paolo Paoletti, MD, Senior Vice President, GlaxoSmithKline Oncology R&D Unit. “While treatment has improved in the past few years with the introduction of targeted therapies, advanced RCC remains a challenging disease. Votrient will join existing targeted therapies toprovide physicians with a new oral treatment option to their patients with advanced renal cell cancer.”

Votrient, a once-daily, oral medication, is an angiogenesis inhibitor which may help prevent the growth of new blood vessels, thereby blocking the growth of kidney cancer tumors that need blood vessels to survive.

The approval of Votrient was supported by a unanimous decision by the FDA’s Oncology Drugs Advisory Committee (ODAC) that the benefit-to-risk profile for Votrient is acceptable for patients with advanced kidney cancer. The ODAC reviewed data from a Phase III clinical trial showing that Votrient reduced the risk of tumor progression or death by 54 percent compared to placebo, regardless of prior treatment.

In this Phase III trial, the overall median PFS was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naïve patients who received Votrient experienced 11.1 months of median progression-free survival (PFS) versus 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with Votrient versus 4.2 months with placebo.

The most common adverse events occurring in ≥20% of subjects treated with Votrient included diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Grade 3/4 adverse events among these toxicities that differed by≥2% included abnormal liver function, hypertension, diarrhea, asthenia, and abdominal pain. Laboratory abnormalities occurring in >10% of patients and more commonly (>5%) in the pazopanib arm included increased transaminases, hyperglycemia, leukopenia, hyperbilirubinemia, neutropenia, hypophosphatemia, thrombocytopenia, lymphocytopenia, hyponatremia, hypomagnesemia, and hypoglycemia. Drug-related deaths were observed in 1.4% of 290 patients and included hepatic failure (n=2), stroke (n=1), and perforation (n=1). Hepatic dysfunction is included as a boxed warning in the product label. Other Warnings and Precautions in the label relate to QT prolongation and torsade de pointes, hemorrhagic events, arterial thrombotic events, gastrointestinal perforation and fistula, hypertension, impaired wound healing, hypothyroidism, proteinuria, and pregnancy.

Votrient has a broad clinical program across multiple tumor types, with study details available at www.clinicaltrials.gov. More than 2,000 patients have been treated to date in clinical trials. Votrient is not yet approved in any country other than the U.S.

Votrient™ is the proposed registered trademark to be used in the United States and Europe.

Hope for people suffering from systemic lupus erythematosus

GlaxoSmithKline and Human Genome Sciences announce full presentation at ACR of positive phase 3 study results for Benlysta in systemic lupus erythematosus

Benlysta (belimumab) significantly reduced SLE disease activity, disease flare rates and fatigue; significantly delayed time-to-first SLE disease flare; reduced prednisone use and improved health-related patient quality of life in the BLISS-52 study

GlaxoSmithKline PLC (GSK) and Human Genome Sciences, Inc. (Nasdaq: HGSI) announced the full presentation of results from BLISS-52, the first of two pivotal Phase 3 trials of Benlysta™ (belimumab) in seropositive patients with systemic lupus erythematosus (SLE). The data, which were presented today in Philadelphia at the 73rd Annual Scientific Meeting of the American College of Rheumatology (ACR), demonstrated that, in BLISS-52, belimumab plus standard of care achieved a clinically and statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care. Study results also showed that belimumab was generally well tolerated, with adverse event rates comparable between belimumab and placebo treatment groups.

“The BLISS-52 Phase 3 results presented at ACR demonstrated that the efficacy of treatment with Benlysta plus standard of care was superior to that of placebo plus standard of care,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “These data were statistically significant and were strongly supported across multiple measures of clinical effect and multiple time-points. Of note, a greater percentage of patients receiving Benlysta were able to reduce their use of steroids.”

Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “We have been pleased by the consistency of benefit demonstrated by belimumab in the BLISS-52 study, and we hope to confirm these results in the second Phase 3 study which is to report shortly. We very much hope that we will be able to deliver a new option for the treatment of this debilitating disease.”

Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors. No new drug for lupus has been approved by regulatory authorities in more than 50 years. Belimumab is being developed by HGS and GSK under a co-development and commercialisation agreement entered into in August 2006. Results from BLISS-76, the second Phase 3 trial of belimumab, will be announced on 02 November 2009. Assuming the results from BLISS-76 are positive, HGS and GSK plan to submit marketing applications in the United States, Europe and other regions in the first half of 2010.

Key Findings Presented at ACR from Phase 3 BLISS-52 Study

Professor Sandra V. Navarra, M.D., a principal investigator and Head of Rheumatology at the University of Santo Tomas, Manila, The Philippines, presented efficacy and safety results from the Phase 3 BLISS-52 study. “These data suggest that belimumab could emerge to play an important role in the future treatment of patients with SLE,” said Dr. Navarra. “Patients with SLE can experience a range of potentially debilitating symptoms, some of which can involve major organs and flare unpredictably several times during a year. For patients with severe symptoms, SLE can be fatal. It is a disease that represents a major unmet medical need. We are very encouraged by the BLISS-52 data and look forward to the results of the BLISS-76 study, which we hope will confirm the therapeutic potential of belimumab.”

Among 865 patients randomised and treated, belimumab met its primary efficacy endpoint by achieving a superior SLE patient response rate at Week 52 vs. placebo.

* A clinically and statistically significant improvement was shown in patient response rate for belimumab plus standard of care vs. placebo plus standard of care: 57.6% for 10 mg/kg belimumab, 51.4% for 1 mg/kg belimumab, and 43.6% for placebo (p=0.0006 and p=0.013 for 10 mg/kg and 1 mg/kg belimumab, respectively).
* The BLISS-52 patient response rate was based on the SLE Responder Index (SRI), which defines patient response by an improvement in SELENA SLEDAI score of 4 points or greater, with no clinically significant BILAG worsening, and no clinically significant worsening in Physician’s Global Assessment.
* There were more responders in the 10 mg/kg belimumab group compared to the placebo group between Weeks 4 and 8 of the study and this difference was statistically significant at Week 16 (p<0.05 for 10 mg/kg belimumab vs. placebo). The improvement was statistically significant and sustained for 10 mg/kg and 1 mg/kg belimumab from Week 24 and Week 28, respectively, through 52 weeks (p<0.05 for both belimumab treatment groups).
* The improvement in patient response rate was generally consistent across subgroups.
* A dose response trend was observed, with a greater rate of patient response in the 10 mg/kg belimumab dose group.
* Results for each individual component of the SRI strongly support the overall improvement shown for the primary endpoint.

Key findings of the BLISS-52 study also included the following:

FLARES

* Belimumab significantly delayed time to first SLE disease flare versus placebo (SLE Flare Index/SFI): median = 119 days for 10 mg/kg belimumab, 126 days for 1 mg/kg belimumab, and 84 days for placebo (p=0.0036 and p=0.0026 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo).
* The risk of having severe SLE disease flares (SFI) was reduced over 52 weeks by 43% in the 10 mg/kg belimumab treatment group and by 24% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.0055 and p=0.1342 for 10 mg/kg and 1 mg/kg belimumab, respectively).
* The risk of having 1 BILAG A (severe flare) or more than 1 BILAG B (moderate flare) organ domain score was reduced by 42% in the 10 mg/kg belimumab treatment group and by 13% in the 1 mg/kg treatment group vs. placebo (p=0.0016 and p=0.3722 for 10 mg/kg and 1 mg/kg belimumab, respectively).

DISEASE ACTIVITY

* A significantly greater percentage of patients receiving belimumab achieved a reduction in SELENA SLEDAI score of at least 4 points by Week 52 (p=0.0024 and p=0.019 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo), with improvement observed for 10 mg/kg belimumab within 4-8 weeks and reaching statistical significance at Week 16 and Weeks 24-52 (p<0.05 vs. placebo).
* A significantly greater improvement in Physician’s Global Assessment (PGA) at Week 52 was observed in the belimumab treatment groups, with a mean percentage change from baseline of 45.7% for 10 mg/kg belimumab, 39.3% for 1 mg/kg belimumab, and 27.8% for placebo (p<0.0001 and p=0.004 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo). The improvement in PGA was observed within 4-8 weeks and was sustained through 52 weeks (p<0.05 for both belimumab treatment groups).

STEROID USE

* In patients who were receiving >7.5 mg per day of prednisone at baseline, a significantly higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study (p=0.025). A higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study, but the difference did not reach a level of statistical significance (p=0.053).
* In patients who were receiving <7.5>7.5 mg per day during the last 20 weeks of study (p<0.05). Fewer increases in prednisone use also were observed in the 1 mg/kg belimumab treatment group vs. the placebo group during the last 20 weeks of study, but the difference did not reach a level of statistical significance.

FATIGUE AND QUALITY OF LIFE

* Improved fatigue scores were observed in the 10 mg/kg belimumab treatment group vs. the placebo group within 4-8 weeks, and both belimumab treatment groups achieved statistically significant improvement of fatigue by Week 52 (FACIT-Fatigue Scale; p<0.05 for both belimumab groups vs. the placebo group).
* Improvement in health-related quality of life (HRQOL) as measured by the SF-36 Physical Component Summary (PCS) score at Week 24, a prespecified major secondary endpoint, was not significantly different among treatment groups. HRQOL improvement as measured by the SF-36 PCS score at Week 52 was significantly greater in both belimumab treatment groups vs. the placebo group (p=0.025 for 10 mg/kg and p=0.027 for 1 mg/kg belimumab, respectively).

SAFETY

* In BLISS-52, belimumab was generally well tolerated, with rates of overall adverse events, serious adverse events, infections and fatalities comparable between belimumab and placebo treatment groups. Serious infections were reported in 5.9% of patients on placebo and 6.1% of patients on belimumab. The most common adverse events were headache, arthralgia, upper respiratory tract infections, urinary tract infection and influenza, and were also comparable between belimumab and placebo treatment groups. No malignancies were reported.

About the Benlysta (belimumab) Phase 3 Development Programme

The Phase 3 development programme for belimumab includes two double-blind, placebo-controlled, multi-centre Phase 3 superiority trials – BLISS-52 and BLISS-76 – to evaluate the efficacy and safety of belimumab plus standard of care, versus placebo plus standard of care, in seropositive (HEp-2 ANA > 1:80 and/or anti-dsDNA > 30 IU/mL) patients with SLE. This is the largest clinical trial programme ever conducted in lupus patients. BLISS-52 randomised and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. BLISS-76 enrolled and randomised 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. The design of the two trials is similar, but the duration of therapy in the two studies is different – 52 weeks for BLISS-52 and 76 weeks for BLISS-76. The data from BLISS-76 will be analysed after 52 weeks in support of a potential Biologics License Application in the United States and Marketing Authorisation Applications in Europe and other regions. HGS designed the Phase 3 programme for belimumab in collaboration with GSK and leading international SLE experts, and the programme is being conducted under a Special Protocol Assessment agreement with FDA.

The primary efficacy endpoint of BLISS-52 and BLISS-76 is the patient response rate at Week 52 based on the SLE Responder Index, which is defined by: (1) a reduction from baseline of at least 4 points on the SELENA SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician’s Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which indicates a moderate flare of disease activity).

Analysis for the primary endpoint is based on intention-to-treat (ITT) and adjusted for baseline stratification factors, including SELENA SLEDAI score, proteinuria and race.

In each of the two Phase 3 trials, patients were randomised to one of three treatment groups: 10 mg/kg belimumab (BLISS-52, n=290), 1 mg/kg belimumab (BLISS-52, n=288), or placebo (BLISS-52, n=287). Patients are dosed intravenously on Days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All patients receive standard of care therapy in addition to the study medication. Safety is reviewed by an independent Data Monitoring Committee throughout both studies.

About Benlysta (belimumab)

Belimumab is an investigational human monoclonal antibody drug that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS®. BLyS is a naturally occurring protein discovered by HGS that is required for the development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. In lupus and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies – antibodies that attack and destroy the body’s own healthy tissues. The presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical studies suggest that belimumab can reduce autoantibody levels in SLE. BLISS 52 results suggest that belimumab can reduce SLE disease activity. Results from a second Phase 3 trial, BLISS-76, are expected on November 2, 2009.

About Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disease. Approximately five million people worldwide, including approximately 1.5 million in the United States, suffer from various forms of lupus, including SLE. Lupus can occur at any age, but appears mostly in young people ages 15 to 45. About 90 percent of those diagnosed with lupus are women. African-American women are about three times more likely to develop lupus, and it is also more common in Hispanic, Asian and American Indian women. Symptoms may include extreme fatigue, painful and swollen joints, unexplained fever, skin rash and kidney problems. Lupus can lead to arthritis, kidney failure, heart and lung inflammation, central nervous system abnormalities, inflammation of the blood vessels and blood disorders. For more information on lupus, visit the Lupus Foundation of America at www.lupus.org, the Lupus Research Institute at www.lupusresearchinstitute.org, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at www.niams.nih.gov, or Lupus Europe at www.elef.rheumanet.org.

Immunization prevents 2.5 million child deaths every year

Vaccination against vaccine-preventable diseases is essential to reaching the Millennium Development Goal 4 on reducing under-five mortality by two thirds by 2015, according to World Health Organisation. Immunization is also a key strategy to ensure global health security and for responding to the threat of emerging infections such as pandemic influenza.

For the first time in documented history, the number of children dying every year has fallen below ten million — partly the result of improved access to immunization, integrated delivery of essential health interventions, as well as clean water and sanitation.

Immunization prevents an estimated 2.5 million child deaths every year in all age groups from diphtheria, tetanus, pertussis (whooping cough), and measles. It is one of the most successful and cost-effective public health interventions.

More children than ever are being reached with immunization. In 2008, an estimated 106 million children under the age of one were vaccinated with three doses of diphtheria―tetanus―pertussis (DTP3) vaccine. These children are protected against infectious diseases that can have serious consequences like illness, disability or death.

Despite the progress, an estimated 24 million children under the age of one did not receive the DTP3 vaccine doses in 2008. About three quarters of these children live in ten countries: Chad, China, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan and Uganda.

An estimated 1.3 million infants and young children die every year from pneumococcal disease and rotavirus diarrhoea. A large number of these deaths can be prevented through vaccination.

A large number of vaccine products are currently in the pipeline and are expected to become available by 2012. More than 80 candidate vaccines are in the late stages of clinical testing. About 30 of these candidate vaccines aim to protect against major diseases for which no licensed vaccines exist, such as dengue and malaria.

The Meningitis Vaccine Project is working on a new meningococcal vaccine. Meningitis A epidemics severely affect certain sub―Saharan countries. A first―generation malaria vaccine has also demonstrated some level of efficacy in young children and may be available by 2015.

Vaccination has led to the elimination of measles in the WHO Region of the Americas. Global measles mortality has decreased by 74% from 750 000 deaths in 2000 to 197 000 deaths in 2007, thanks to intensified vaccination campaigns.

Polio has been eradicated in three of WHO’s six regions and is today endemic in only four countries ― Afghanistan, India, Nigeria and Pakistan ― down from 125 countries in 1988. Annual deaths from neonatal tetanus have fallen to an estimated 128 000, down from 790 000 deaths in 1988.

Immunization not only protects children from vaccine―preventable diseases. It also serves as a means to deliver other life―saving measures, such as vitamin A supplements to prevent malnutrition, insecticide―treated nets for protection against malaria and deworming medicine for intestinal worms.

Adults With Depression Still Struggle Due to Lack of Information

A new survey of 2,001 adults living with depression revealed that despite being diagnosed for an average of 12 years, many unknowingly took actions that could have sabotaged their chances of getting well. Furthermore, on average, it took about six years for respondents to seek diagnosis from a health care professional, suggesting these adults may have been coping with depression for as long as 18 years.

Nearly three in five (57 percent) of those who delayed seeking a diagnosis felt they could manage their own depression symptoms. Among respondents who had taken antidepressants for depression, nearly half (47 percent) did not discuss when it might be necessary to change medications with their doctor, despite the fact that they were still experiencing depressive symptoms. Among those who have stopped taking antidepressants, about two in five (41 percent) did so without telling their doctor. More than 70 percent noted that talk therapy should always be part of a depression treatment plan, yet only 22 percent were currently enrolled in talk therapy.
"The survey strongly suggests that many people living with depression are unaware or are 'missing pieces' of vital information that may be preventing them from getting well," said Dr. Susan Kornstein, professor of psychiatry and obstetrics and gynecology at Virginia Commonwealth University. "Depression needs to be treated by a health care professional. To increase the likelihood of recovery from depression, it's important that people with depression have a comprehensive treatment plan that may include medications, psychotherapy and lifestyle changes. The goal is to help them to recovery." Depression, which includes a variety of symptoms, is a highly treatable illness, but it can become more difficult to treat the longer it goes undiagnosed or undertreated.

The survey showed that among those who waited six months or more to be diagnosed, 69 percent reported they delayed diagnosis because they lacked knowledge about depression or lacked basic facts about available depression treatments and where to go for help. Additionally, among those who wanted more information about depression treatment at the time of diagnosis, 64 percent said they wanted to know what it means to "get well.". Surprisingly, 91 percent have been prescribed an antidepressant for depression, but among them, just seven percent felt very knowledgeable about all basic aspects of the treatment.

Pfizer’s Oral JAK Inhibitor Demonstrates Response In Patients With Active Rheumatoid Arthritis

Final Phase 2 Analyses Presented at the American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting

Pfizer Inc announced that 24-week data from two clinical studies of the oral JAK inhibitor, CP-690,550, confirmed statistically significant ACR20 response and DAS28 remission rates for several doses versus placebo when given alone or in combination with methotrexate for patients with active rheumatoid arthritis (RA). The findings, which were presented at the 2009 ACR/ARHP Annual Scientific Meeting in Philadelphia, represent the final analyses from two Phase 2 trials evaluating the effect of CP-690,550 over 24 weeks.

“These data suggest that CP-690,550 could represent a promising advance for patients with rheumatoid arthritis,” said Michael Berelowitz, MD, senior vice president Clinical Development and Medical Affairs for Pfizer Specialty Care. “Our Phase 3 program is currently underway with enrollment progressing as planned, and we are hopeful that data from these trials will validate the Phase 2 results.”

Efficacy as Monotherapy at 24 weeks

Data presented from a six-month, double-blind, placebo-controlled Phase 2B study (Study A3921035), which evaluated 384 patients with active RA who had not responded to disease-modifying anti-rheumatic drugs (DMARDs), showed that patients treated with 5, 10 and 15 mg twice-daily doses of CP-690,550 dosed without background methotrexate experienced statistically significant ACR response rates and DAS28 remission rates at week 24 as compared to placebo. These results were consistent with the previously reported primary analysis of ACR response at week 12.

24-Week efficacy results are as follows:
	Treatment		ACR20(%)		ACR50(%)		ACR70(%)		DAS28 Remission(%)
	1 mg		24.1		7.4		5.6		5.8
	3 mg		37.3		27.5*		13.7		13.7*
	5 mg		51.0*		34.7*		20.4*		14.6*
	10 mg		65.6***		44.3***		37.7***		21.3**
	15 mg		66.7***		54.4***		33.3**		21.1**
	Placebo		25.4		10.2		6.8		1.8
*p≤0.05 **p≤0.01 *** p≤0.0001

All patients were randomized to either placebo or one of the studied doses of CP-690,550. This study also included adalimumab (40 mg subcutaneously every other week) as an active control in the first 12 weeks of the study.

Efficacy in Combination with Methotrexate at 24 weeks

Data from a second six-month, double-blind, placebo-controlled Phase 2b study (Study A3921025) evaluating 507 patients whose RA was active despite ongoing treatment with methotrexate demonstrated that patients treated with 3, 10 and 15 mg twice-daily and 20 mg once-daily doses of CP-690,550 in addition to stable background methotrexate experienced statistically significant ACR response rates and DAS28 remission rates at week 24 as compared to placebo. These results were consistent with previously reported primary analysis of ACR response at week 12.

24 week efficacy results are as follows:
	Treatment		ACR20(%)		ACR50(%)		ACR70(%)		DAS28 Remission(%)
	1 mg		41.4		31.4		20.0*		13.2
	3 mg		52.9*		27.9		19.1*		23.9*
	5 mg		47.9		33.8		19.7*		28.6*
	10 mg		55.4*		35.1		17.6		29.6*
	15 mg		58.7*		44.0*		30.7**		29.7*
	20 mg		52.5*		38.8*		23.8*		22.8*
	Placebo		34.8		23.2		7.3		10.5
*p≤0.05 **p≤0.01

This study evaluated CP-690,550 doses of 1, 3, 5, 10 and 15 mg twice daily and 20 mg once daily. All patients were maintained on their stable background of methotrexate and randomized to either addition of placebo or one of the studied doses of CP-690,550.

In both studies, the most commonly-reported treatment-emergent adverse events were urinary tract infections, headache, and diarrhea. Most adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, and total cholesterol were consistent with what has been observed in previous studies of CP-690,550 in RA. For patients dosed on background methotrexate, transaminase increases were also consistent with what had been reported in interim analyses in previous studies of CP-690,550 in RA.

All studies were sponsored by Pfizer Inc.

ORAL Trials: Advancing Clinical Research for RA

The Phase 3 program, which is known as the ORAL (Oral CP-690,550 Rheumatoid Arthritis Phase 3 TriaLs) Program, consists of six Phase 3 studies at more than 350 locations in 35 countries worldwide (www.ORALtrials.com.)

About CP-690,550

CP-690,550 is an oral, selective, potent inhibitor of the JAK family of enzymes. In cell-based assays, CP-690,550 has been shown to inhibit JAK-3 and JAK-1 with functional selectivity over JAK-2. By inhibiting these enzymes, which affect the signaling of multiple cytokines (proteins released by cells to communicate with other cells) that are involved in a broad spectrum of inflammatory and autoimmune diseases, treatment with CP-690,550 may lead to clinically meaningful improvement for patients.

CP-690,550 is also being evaluated as a potential treatment for psoriasis, Crohn’s disease, ulcerative colitis and solid organ transplant.

Vorinostat Reduces Formation of Brain Metastases in Mice

The drug vorinostat is able to cross the blood-brain barrier and reduce the development of large metastatic tumors in mice brains by 62 percent when compared to mice that did not receive the drug, according to a new study. In humans, the drug has been approved by the U.S. Food and Drug Administration for the treatment of a cancer called cutaneous T-cell lymphoma but can be used experimentally to study its effectiveness against other cancers. This research, by investigators at the National Cancer Institute (NCI) and their collaborators, appears online in Clinical Cancer Research.

For people, while various therapies are improving the survival of breast cancer patients, the incidence of breast cancer spreading to the brain is increasing. Brain metastases of breast cancer have proven to be largely untreatable because the blood-brain barrier, which arises from the specialized structure of blood capillaries in the brain, severely limits drug access and many drugs are actively transported out of brain at this barrier. Consequently, the one-year survival estimate for breast cancer patients after a diagnosis of brain metastasis is only about 20 percent.

Vorinostat has been found to slow the growth of primary tumors of several different types of cancer in mice. Previous studies have suggested that the drug can be taken up by the brain, although little was known about its effects on metastatic tumors. Therefore, to study the effect of vorinostat on the formation of brain metastases, scientists used a mouse model of human breast cancer. Human breast cells were cultured in the laboratory and were injected into mice with compromised immune systems. The breast cancer cells then migrated to the brain, forming metastases. "Drugs that can cross the blood-brain barrier and reduce the size and incidence of metastatic tumors are urgently needed," said Patricia S. Steeg, Ph.D., study author, Center for Cancer Research, NCI. The researchers found that vorinostat was absorbed readily into normal mouse brains, and accumulation of the drug was up to three-fold higher in some metastases treated with this drug when compared to surrounding brain tissue. Vorinostat also reduced the development of tiny tumors (micrometastases) in mice by 28 percent when compared with mice that did not receive this therapy.

www.nci.nih.gov

3.2 Million Europeans Are Diagnosed With Cancer Every Year

Every year 3.2 million Europeans are diagnosed with cancer, mostly breast, colorectal or lung cancers, according to European Commission report. In 2006 in Europe, there were an estimated 3 191 600 cancer cases diagnosed (excluding nonmelanoma skin cancers) and 1 703 000 deaths from cancer. The most common form of cancers was breast cancer (429 900 cases, 13.5% of all cancer cases), followed by colorectal cancers (412 900, 12.9%) and lung cancer (386 300, 12.1%). Lung cancer, with an estimated 334 800 deaths (19.7% of total), was the most common cause of death from cancer, followed by colorectal (207 400 deaths), breast (131 900) and stomach (118 200) cancers, according to European Society for Medical Oncology. Breast cancer is the leading cause of death from cancer in women in Europe. A fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies. These declines have been attributed to the combined effect of earlier detection and improving treatment, but it was observed mainly in young women, and because of the ageing of the European population the number of deaths from breast cancer is still rising (130 000 in 2004, 132 000 in 2006).

Excess body weight causes over 124,000 new cancers a year

At least 124,000 new cancers in 2008 in Europe may have been caused by excess body weight, according to estimates from a new modelling study. The proportion of cases of new cancers attributable to a body mass index of 25kg/m² or more were highest among women and in central European countries such as the Czech Republic, Latvia, Slovenia and Bulgaria. “As more people stop smoking and fewer women take hormone replacement therapy, it is possible that obesity may become the biggest attributable cause of cancer in women within the next decade”, Dr Andrew Renehan, the lead author of the study, said.
Dr Renehan, who is a senior lecturer in cancer studies and surgery at the University of Manchester (UK), and his colleagues in the UK, The Netherlands and Switzerland, created a sophisticated model to estimate the proportion of cancers that could be attributed to excess body weight in 30 European countries. Using data from a number of sources including the World Health Organisation and the International Agency for Research on Cancer, they estimated that in 2002 (the most recent year for which there are reliable statistics on cancer incidence in Europe) there had been over 70,000 new cases of cancer attributable to excess BMI out of a total of nearly 2.2 million new diagnoses across the 30 European countries. Then, the researchers projected the figures forward to 2008, taking into account what was known about shifts in the distribution of BMI, the dramatic decline in women’s use of hormone replacement therapy (HRT) from 2002 onwards following research that showed it increased the risk of breast cancer, and the wider use of PSA screening for prostate cancer in men.

They found that the number of cancers that could be attributed to excess body weight increased to 124,050 in 2008. In men, 3.2% of new cancers could be attributed to being overweight or obese and in women it was 8.6%. The largest number of obesity-related new cancers was for endometrial cancer (33,421), post-menopausal breast cancer (27,770) and colorectal cancer (23,730). These three accounted for 65% of all cancers attributable to excess BMI.

The number of new cases of obesity-related oesophageal cancer was particularly high in the UK relative to the rest of Europe. “This country accounts for 54% of new cases across all 30 countries,” said Dr Renehan. “This may be due to synergistic interactions between smoking, alcohol, excess body weight and acid reflux – and is currently an area where research is required.”

120 Million People Worldwide Are Depressed

Depression affects around 120 million people worldwide and by the year 2020 will be the 2nd most common health problem in the world, according to World Health Organisation (WHO). Around 20% of the world's children and adolescents are estimated to have mental disorders or problems. About 10-15% of older people are thought to suffer from depression, and the incidence in nursing homes is much higher. In 2002, depression accounted for 4.5% of the worldwide total burden of disease. The UK has one of the highest rates of self harm in Europe, at 400 per 100,000 population. 1 in 4 British adults experience at least one diagnosable mental health problem in any one year, and one in six experiences this at any given time, according to The Office for National Statistics Psychiatric Morbidity report. Depressive disorders affect approximately 18.8 million American adults or about 9.5% of the U.S. population age 18 and older in a given year. 54% of people believe depression is a personal weakness. 15% of depressed people will commit suicide. 80% of people who see physicians are depressed.

Depression often co-occurs with other illnesses and medical conditions: 25% of cancer patients experience depression; 10-27% of post-stroke patients experience depression; 1 in 3 heart attack survivors experience depression; 1 in 3 HIV patients may experience depression; 50% of Parkinson's disease patients may experience depression; 50-75% of eating disorder patients (anorexia and bulimia) experience depression; 27% of individuals with substance abuse disorders (both alcohol and other substances) experience depression; 8.5-27% of persons with diabetes experience depression.

Women are almost twice as likely to become depressed as men. The higher risk may be due partly to hormonal changes brought on by puberty, menstruation, menopause and pregnancy. About 10 to 15 percent of women experience postpartum depression after giving birth.

Major depressive disorder, also called major depression, is characterized by a combination of symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy once–pleasurable activities. Major depression is disabling and prevents a person from functioning normally. An episode of major depression may occur only once in a person's lifetime, but more often, it recurs throughout a person's life.

Mild to moderate depression can often be successfully treated with psychotherapy, sometimes known as "talk therapy". Exercise can help reduce feelings of depression by increasing the body's supply of endorphins, chemicals in the body that increase the feeling of well being.

For some cases, especially in more severe depression, psychotherapy combined with medication may be needed. After a complete evaluation, your health care professional will decide if medication is appropriate in your case and what medication or combination of medications will work best for you. Medications affect individuals differently and it may be necessary to adjust dosages or even change medications, depending on your response and reaction. Commonly prescribed types of antidepressants include SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), MAOIs (monoamine oxidase inhibitors), and tricyclics. Side effects can vary among these medications, but may include nausea, headache, insomnia, nervousness, sexual problems, drowsiness during the day, bladder problems, blurred vision, and dry mouth.

In some situations in which medications and psychotherapy have not been effective, depression may be treated by electroconvulsive therapy (ECT). Also known as "shock therapy", ECT has come a long way from its early days.

Antidepressants: selective serotinin reuptake inhibitors: Fluoxetine, Sertraline, Fluovoxamine, Paroxetine, Citalopram, Venlafaxine.

Tricyclic antidepressants (tricyclics): Clomipramine, Imipramine.

Monoamine oxidase inhibitors (MAOIs): Tranylcypromine, Isoprocarboxazid.

Benzodiazepines: Clonazepam, Alprazolam, Lorazepam.

Azipirones: Buspirone.

Beta blockers: Propanolol

WHO data suggests that depression causes 6% of the burden of all diseases in Europe in terms of disability adjusted life years. The cost of depression corresponds to 1% of the total economy of Europe.