Red meat consumption rheumatoid arthritis link

Study indicates high levels of red meat consumption as an independent risk factor in the development of inflammatory
arthritis,


A chronic inflammatory disease of the immune system, rheumatoid arthritis (RA) has been linked to a combination of genetic
and environmental factors. Aspects of lifestyle may explain as much as 40 percent of the risk.

Cigarette smoking has
consistently been found to play a role in RA's development. The role of nutritional factors is less certain. Studies have
suggested the protective benefits of eating fish, the dangers of drinking coffee, and a reduction in disease risk for women
who enjoy alcohol in moderation. Such associations, however, are still wide open to debate and further research.


Recently, a team of British researchers found that a diet lacking in fruit, especially varieties high in vitamin C, increases
the risk of inflammatory arthritis, a common early sign of RA, as much as three-fold. Building on this compelling finding,
they set out to investigate the association of other dietary habits with the onset of RA. Their results, published in the
December 2004 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), indicate a high level of red meat consumption as an
independent risk factor for inflammatory arthritis.


Led by Professors Alan Silman and Deborah Symmons at the University of Manchester, the team drew its subjects from a large,
established research sample--over 25,000 men and women between the ages of 45 and 75 enrolled in the European Prospective
Investigation of Cancer in Norfolk, England. Within this population, 88 new patients with inflammatory arthritis, affecting
at least two major joints, were identified.


Nearly 40 percent of these patients satisfied the American College of Rheumatology criteria for RA at baseline. The patients
were then matched, for age, sex, and body mass index, with 176 controls. At the study's onset, each participant completed a
detailed 7-day food diary, with advance instruction on measuring food portions to help them be as specific as possible in
recording their intake. Each participant also supplied information on his or her past and present status as a smoker.



Patients were more likely to have been former smokers; only 35 percent of the patients had never smoked compared with 85
percent of the controls. In terms of dietary factors, patients and controls were similar in most areas, including intake of
total calories, fat grams, and vitamin D, as well as coffee, tea, and alcohol consumption. Patients had a lower intake of
vitamin C, although the association of this factor with disease risk was not as strong as it was in the team's previous
study. The most striking difference between the two groups was directly related to red meat consumption. After adjusting for
smoking and other possible dietary confounders, patients with the highest level of red meat consumption had a two-fold risk
for the development of RA. Patients who consumed high levels of red meat combined with other meat products showed similar
high risk levels. Interestingly, a higher level of protein intake from all dietary sources was also associated with an
increased disease risk, while higher levels of dietary fats, including saturated fat, did not have an impact.


Routinely eating burgers and steak, however, may only influence people with a predisposition for RA. "It may be that the high
collagen content of meat leads to collagen sensitization and consequent production of anticollagen antibodies, most likely in
a subgroup of susceptible individuals," the authors note. "Meat consumption may be linked to either additives or even
infectious agents, but, again, there is no evidence as to what might be important in relation to RA."


"A high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for
a group of persons with an increased risk from other lifestyle causes," Dr. Pattison and colleagues conclude. "It is unclear
whether the association is a causative one."


Article: "Dietary Risk Factors for the Development of Inflammatory Polyarthritis: Evidence for a Role of High Level of Red
Meat Consumption," Dorothy J. Pattison, Deborah P.M. Symmons, Mark Lunt, Ailsa Welch, Robert Luben, Sheila A. Bingham,
Kay-Tee Khaw, Nicholas E. Day, and Alan J. Silman, Arthritis & Rheumatism, December 2004; 50:12; pp. 3804-3812.


John Wiley & Sons, Inc

Lexicon Initiates Phase 2 Clinical Trial Of LX2931 In Patients With Rheumatoid Arthritis

Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced that it has initiated a Phase 2 clinical trial of LX2931 in patients with rheumatoid arthritis. LX2931 is an orally-delivered, small molecule drug candidate that has recently completed Phase 1 testing in normal volunteers. Lexicon also successfully completed a drug-drug interaction (DDI) study of LX2931 with methotrexate in patients with rheumatoid arthritis, with no clinically significant drug-drug interactions observed.


"We believe that, as an oral therapy, LX2931 could have advantages over current biologic therapies in treating patients with rheumatoid arthritis," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "LX2931 has demonstrated potent anti-inflammatory activity in preclinical models of arthritis and inflammation and, importantly, has been well tolerated in combination with methotrexate, the current standard of care first-line therapy."


LX2931 inhibits sphingosine-1-phosphate (S1P) lyase, an enzyme identified by Lexicon scientists as a promising new target on a pathway associated with regulation of the human immune system. Lexicon has previously shown that genetically "knocking out" or "knocking down" S1P lyase in mice substantially decreased the inflammatory response in multiple models of arthritis, inflammation and transplantation.


The Phase 2 clinical trial is designed as a 12-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX2931 and its effects on symptoms associated with rheumatoid arthritis. The study will include multiple centers in the United States and Eastern Europe. The company expects to enroll up to 120 patients with rheumatoid arthritis on stable methotrexate therapy. Three dose levels will be evaluated: a 70 mg dose, a 110 mg dose and a 150 mg dose, each administered once daily. The primary endpoint will be the ACR20, which is defined by the American College of Rheumatology (ACR) as a 20 percent improvement in symptoms associated with rheumatoid arthritis. Multiple secondary endpoints will also be evaluated, including ACR50, ACR70 and DAS28.


In addition to LX2931, Lexicon has two other drug candidates progressing in Phase 2 clinical trials, LX1031 for irritable bowel syndrome and LX1032 for carcinoid syndrome. Furthermore, LX4211 for diabetes has recently completed dosing in a Phase 1 clinical trial.


About Rheumatoid Arthritis


Lymphocytes are a type of white blood cell that play an important role in the immune system. Inappropriate activation of lymphocytes is often associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues and cells. Rheumatoid arthritis is an autoimmune disorder characterized by stiffness, pain, swelling, and limitation of motion in multiple joints. More than 2 million Americans suffer from rheumatoid arthritis, which, if left untreated, can result in disfigurement and disability from irreversible joint damage. According to the National Institutes of Health, autoimmune disorders affect between 14.7 and 23.5 million people in the United States.















About Lexicon


Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company's research team. The company has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.


Safe Harbor Statement


This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX2931 and the potential therapeutic and commercial potential of LX2931. This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX2931 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2008, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.


Source: Lexicon Pharmaceuticals, Inc.

UCB's Cimzia(R) Approved In The U.S. For Adult Patients Suffering From Moderate To Severe Rheumatoid Arthritis

Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) today announced that the U.S. Food and Drug Administration (FDA) has approved Cimzia®, for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). Cimzia® (certolizumab pegol), is a PEGylated anti-TNFa (Tumor Necrosis Factor alpha). The product is currently being developed by UCB. Cimzia is one of several products which utilize Enzon's PEGylation technology, including PEG-INTRON®, Macugen®, and Pegasys®.


"Our PEGylation technology continues to enable very important therapeutics like Cimzia, benefiting patients with a wide variety of diseases," said Jeffrey H. Buchalter, Enzon's chairman and chief executive officer.


About CIMZIA®


Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderate to severely active rheumatoid arthritis. Cimzia® was approved in Switzerland for induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn's disease who have not responded adequately to conventional treatment in September 2007. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.


Source
Enzon Pharmaceuticals, Inc.


View drug information on Cimzia; Macugen; Peg-Intron.

Frequency Of Foot Disorders Differs Between African Americans And Whites

Common foot disorders such as flat feet, corns and bunions are more prevalent among African Americans than in whites, a new study by University of North Carolina at Chapel Hill researchers has found.



African Americans in the study age 45 or older were three times more likely than whites of the same age to have corns or flat feet (medical name: pes planus). In people who were not obese, African Americans were twice as likely to have bunions (hallux valgus) and hammer toes than whites, said Yvonne M. Golightly, PT, PhD, lead author of the study, titled "Racial Differences in Foot Disorders: The Johnston County Osteoarthritis Project," and a post-doctoral fellow at UNC's Thurston Arthritis Research Center. There were no significant differences by race for bunions or hammer toes among obese participants.



"That suggests there is a real racial difference there, that it's not something where obesity is also playing a role," she said.



Tailor's bunions (inflammation of the joint at the base of the little toe) and high arches (medical name: pes cavus) were nearly five times more common among whites than African Americans.



Golightly presented these results of the study, based on data collected as part of UNC's long-running Johnston County Osteoarthritis Project, on Tuesday, Nov. 9, at the annual scientific meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals in Atlanta.



In the study, 1,536 participants were clinically evaluated for foot disorders from 2006 to 2010. Golightly and study co-authors identified the most common foot disorders and used statistical analysis to compare each foot problem by race, controlling for age, body mass index (BMI) and gender.



"These foot disorders are very common among people age 45 and older, and can lead to more serious problems such as falls, decreased physical activity and decreased quality of life," Golightly said.



"The next step in our research is to determine the origin of these disorders," she said. "We're interested in looking at the influence of factors such as genetics, shoe wear, multi-joint osteoarthritis, and what type of work a person does."



Co-authors of the study are Marian T. Hannan, DSc, MPH and Alyssa B. Dufour, MA, both from Hebrew Senior Life in Boston, and Joanne M. Jordan, MD, MPH, Chief of the Division of UNC Rheumatology, Allergy and Immunology, director of the UNC Thurston Arthritis Research Center and principal investigator of the Johnston County Osteoarthritis Project.



Source:

Tom Hughes

University of North Carolina School of Medicine

Number Of Excess Cases Of Coronary Heart Disease Caused By Vioxx, Study

The arthritis drug Vioxx could have caused an estimated 88 000 - 140 000 excess cases of serious coronary heart disease
in the USA since its launch in 1999, concludes a study published online by The Lancet.


Vioxx (rofecoxib) belongs to a class of cyclo-oxygenase 2 (COX-2) inhibitor selective nonsteroidal anti-inflammatory drugs
(NSAIDs), which are prescribed for the treatment of arthritis. Vioxx was withdrawn from the pharmaceutical market at the end
of September 2004 after use of the drug was linked to heart problems.


David J Graham (Office of Drug Safety, US Food and Drug Administration) and colleagues assessed whether coronary heart
disease risk was increased with either high or standard doses of Vioxx compared with other (NSAIDs) or the COX-2 inhibitor
celecoxib (Celebrex), a drug commonly used as an alternative to Vioxx.


They analysed data from 1???4 million people in California who had used NSAIDs from the beginning of 1999 to September 2004.
Patients had received various NSAIDs, including celecoxib (around 40 000 users), ibuprofen (just under a million users),
naproxen (around 435 000 users), and rofecoxib (around 27 000 users). The investigators found that 8143 individuals had
serious coronary heart disease, 1508 of which had sudden cardiac death. Each case was matched by age and sex to four controls
to enable a comparison of coronary heart disease risk among people taking Vioxx and users of other NSAIDs.


People taking Vioxx had a 34% higher chance of coronary heart disease when compared with people who used other NSAIDs.
Coronary heart disease was 1???6 times more likely among people currently taking standard-dose Vioxx compared with those
currently taking celecoxib and 3???6 times more likely among high-dose users. The study also found that people taking naproxen
had a 14% increased risk of coronary heart disease compared with other NSAIDs. Previous studies have suggested that naproxen
protects against coronary heart disease.


Dr Graham comments: "An estimated 88 000-140 000 excess cases of serious coronary heart disease probably occurred in the USA
over the market life of rofecoxib. The US national estimate of the case-fatality rate (fatal acute myocardial infarction plus
sudden cardiac death) was 44%, which suggests that many of the excess cases attributable to rofecoxib use were fatal.



"In the future, when trials show that a new treatment confers a greater risk of a serious adverse effect than a standard
treatment, we must be much more careful about allowing its unrestrained use."


In an accompanying commentary Simon RJ Maxwell and David J Webb (University of Edinburgh, UK) write that after the withdrawal
of Vioxx increased attention will now focus on the cardiovascular safety of other COX-2 inhibitors (coxibs).


Professor Webb concludes: "It now falls to the manufacturers, under the careful review of the regulatory authorities, to
provide all the evidence that this class of drugs is safe, if necessary including studies that directly address
cardiovascular morbidity as a primary outcome.


Indeed, the experience with coxibs underlines the need for full publication of all clinical trial data generated in support
of newly licensed drugs."


Dr David J Graham, Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville,
MD, USA.T) 301 827 3238


Comment Professor David J Webb, Clinical Pharmacology Unit & Research Unit, Department of Medical Sciences, University of
Edinburgh, Western General Hospital, EDINBURGH, EH4 2XU, UK. T) 0131 537 2006


thelancet


View drug information on Vioxx.

Enrollment begins for osteoarthritis initiative

Recruitment has begun for the Osteoarthritis Initiative (OAI), a public-private partnership between the National Institutes of Health and industry that funds a multisite contract to create a resource to hasten discovery of biological markers for osteoarthritis (OA).


Men and women age 45 and older at risk for developing OA and those with early disease are eligible to participate. After an initial screening, four centers around the United States plan to each enroll and follow 1,250 adults for five years (total enrollment of 5,000).

Biological specimens (blood, urine, DNA), images (X-rays and magnetic resonance scans) and clinical data will be collected annually.



Biological markers - physical signs or biological substances that indicate changes in bone or cartilage - are critical in diagnosing and monitoring OA and developing new treatments.

Ultimately, results from the OAI may enable doctors to use biological markers to help identify people at risk for OA and people with OA at risk for disease progression. The markers could also help doctors assess the effectiveness of treatments.



The four clinical centers, selected in the summer of 2002, include the University of Maryland School of Medicine/Johns Hopkins University, the Ohio State University Medical Center, the University of Pittsburgh and the Memorial Hospital of Rhode Island/Brown University.

A data coordinating center at the University of California, San Francisco oversees the study conduct and will manage the resulting data. The Ohio State University and University of Pittsburgh centers enrolled their first participants the week of February 23, and centers in Maryland and Rhode Island will begin enrollment in late March and early April.


The clinical centers may be contacted at:


Ms. Raushanah Kareem

University of Maryland

10 South Pine Street, Room 8-34, MSTF

Baltimore, MD 21201

(410) 706-5791 or (866) 565-KNEE (toll free)


Osteoarthritis Initiative

The Ohio State University

198 McCampbell Hall

1581 Dodd Drive

Columbus, OH 43210

(614) 688-3563 or (800) 251-1175 (toll free)


Study Office/GSPH

University of Pittsburgh

4200 Fifth Avenue

Pittsburgh, PA 15213-9910

(800) 872-3653 (toll free)


Osteoarthritis Initiative

Memorial Hospital of Rhode Island/Brown University

ATTN: Doris Moore

111 Brewster Street, CPCP Building, 2nd Floor

Pawtucket, RI 02860

(800) 877-3347 (toll free)


Osteoarthritis, a degenerative condition whose hallmarks are joint pain and limited movement resulting from progressive loss of cartilage, is the most common type of arthritis, especially among older people. It can occur in any joint, but most often affects the hands, knees, hips or spine. There are currently no treatments, other than surgical joint replacement, that significantly change the course of this joint disease, and clinical trials for new therapies are long, difficult and expensive.



The OAI is a federal contract funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), Office of Research on Women's Health, National Institute of Dental and Craniofacial Research, National Center on Minority Health and Health Disparities and National Center for Complementary and Alternative Medicine, all part of the Department of Health and Human Services' National Institutes of Health. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation; and Pfizer Inc. Private sector funding for the OAI is being managed by the Foundation for the National Institutes of Health.



For information on the OAI, visit The OAI: A Knee Health Study at oai.ucsf/clinics.asp. For general questions, visit niams.nih/ne/press/2001/07_17qa.htm. The NIAMS Office of Communications and Public Liaison (301-496-8190) or the NIA Communications Office (301-496-1752) can also be contacted for information.



The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at niams.nih.



CONTACT:

Liz Freedman

301-496-8190

Smoking And Rheumatoid Arthritis - Evidence Of Harm Accumulates

The role of smoking as a risk factor for rheumatoid arthritis was supported by several studies reported at the ACR.

Japanese researchers who undertook a meta-analysis of sixteen studies concluded that the strongest association between smoking history and RA occurred for Rheumatoid Factor positive men (odds ratio 2.85) (Abstract# 749).

Swedish researchers found that current smokers had a higher risk of severe extra-articular manifestations of RA than non-smokers (odds ratio 2.67).

They speculate that smoking may have an impact on disease mechanisms in RA, including those leading to extra-articular disease.


American College of Rheumatology Annual Congress (ACR)


mabthera-ra

New Data Shows ACTEMRA Inhibits Progression Of Joint Destruction And Improves Physical Function Of Patients With Rheumatoid Arthritis

Roche announced that the innovative new therapy ACTEMRA (tocilizumab) can significantly inhibit structural damage to joints in patients with rheumatoid arthritis (RA) this is a critical measure of effectiveness of an RA treatment. ACTEMRA was also found to improve the patients' physical function after one year of therapy and to significantly increase the disease remission rate.


The results from the LITHE1 trial, being presented at the American College of Rheumatology (ACR) Annual Scientific Meeting in San Francisco, showed that:



-- A greater proportion of patients treated with ACTEMRA in combination with a commonly used RA drug called methotrexate (MTX) benefited from a significant inhibition of structural damage during 12 months of therapy compared to patients treated with MTX alone. The outcome was determined by x-ray evidence of the progression of bone erosions and narrowing of joint spaces. This benefit is important to patients as damage to the joints caused by the disease leads to the disability and pain associated with RA.



-- ACTEMRA improved the patients' ability to perform normal daily activities, as assessed by the Health Assessment Questionnaire (HAQ)2, leading to a better quality of life.



-- Significantly more patients treated with ACTEMRA achieved remission* than those treated with MTX alone (47% vs. 8%). The improvement in remission at one year reinforces the strong remission data seen at 6 months in four additional ACTEMRA phase III trials across multiple RA patient populations.


"The outcome of this study is good news for RA patients as presently many either fail to achieve an adequate response or cannot tolerate therapies currently available," said William M. Burns, Head of the Roche Pharma Division. "New treatment options are needed, particularly those that can target different pathways to bring relief and inhibit joint damage in patients suffering from RA."


"The LITHE study demonstrated that treatment with ACTEMRA inhibited structural joint damage, which is a major cause of disability and loss of physical function for RA patients," said


Joel Kremer, M.D., investigator in the LITHE study and Director of Research at The Center for Rheumatology in Albany, New York. "It is critical to stop joint damage as quickly as possible to avoid joint deformity and to help patients maintain their quality of life."


In the LITHE study, ACTEMRA was generally well tolerated and the overall safety profile after 12 months of treatment was consistent with previously reported 6 month trial data.


ACTEMRA is the first of a new class of drug with a novel mechanism of action that brings new hope to RA patients. It is a humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody which works by suppressing the activity of IL-6, an important trigger of the inflammatory process. This novel mode of action reduces inflammation of the joints and relieves the systemic effects of RA.















Rheumatoid Arthritis - A High Unmet Medical Need


Rheumatoid arthritis is thought to affect over 21 million people worldwide. It is a progressive autoimmune disease characterized by inflammation of the membrane lining in the joints throughout the body. This inflammation causes distortion of the joint and impaired function accompanied by pain, stiffness and swelling and ultimately leading to irreversible joint destruction and disability. In addition, the systemic symptoms of RA include fatigue, anaemia, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a daily basis.


About the LITHE study


The LITHE study, a randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy of TCZ plus MTX in preventing structural joint damage and improving physical function. LITHE is an international study, including 15 countries and 1196 patients with moderate to severe RA who had an inadequate response to MTX. In this randomized study, patients received either ACTEMRA (4 mg/kg or 8 mg/kg, one infusion every four weeks) in combination with methotrexate or methotrexate alone. The results presented are from a planned 12-month analysis of a 2-year study. At 52 weeks, total Genant-modified Sharp Score change from baseline for the ACTEMRA 8mg + MTX, 4mg +MTX, and MTX alone groups were: 0.29, 0.34 and 1.1 respectively. The percentage of patients achieving no progression in total Genant-modified Sharp Score were 85%, 81% and 67%.The HAQ-DI AUC change from baseline, adjusted mean scores were: -144.1, -128.4 and -58.1 respectively. DAS28 clinical remission (

GlaxoSmithKline And Genmab Initiate Ofatumumab Rheumatoid Arthritis Phase III Programme

GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN) announced the initiation of the Phase III programme with ofatumumab to treat rheumatoid arthritis (RA). The programme will commence with two studies (OFA110635/GEN410 and OFA110634/GEN411), which will be conducted outside the US, in two distinct patient populations. One study will be in patients who have had an inadequate response to methotrexate therapy; and the other in patients who have had an inadequate response to TNF-alpha antagonist therapy. Further studies to support the programme are planned for 2008.


Each study will evaluate the efficacy of ofatumumab in reducing the clinical signs and symptoms in RA patients after a single course of ofatumumab and comprises of a 24 week blinded period followed by a 120 week open-label period during which re-treatment will be studied. The primary endpoint in each study is ACR20 at 24 weeks.


"This brings us closer to our goal of broadening the treatment options for patients with this painful and debilitating disease" said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab. "From the data to date, we believe that ofatumumab has real potential. Now that Phase 3 studies are underway in multiple indications we are moving closer to realising this potential and bringing this important treatment to patients."


"We are very pleased that our collaboration with Genmab has progressed so that we can now move to the next step of the clinical trial programme," said Dr Moncef Slaoui, Chairman of Research and Development, GlaxoSmithKline.


Ofatumumab is an investigational, fully human, next generation monoclonal antibody that targets a unique epitope of the CD20 receptor on the surface of B-cells. This epitope is different than other anti-CD20 antibodies currently available or in development.


About the Trials:


OFA110635/GEN410 - Clinical efficacy and safety of ofatumumab in adult RA patients who have had an inadequate response to methotrexate


A total of approximately 250 patients who had an inadequate response to methotrexate therapy will be enrolled. In the double-blind period, patients will be randomised to receive two 700 mg doses of ofatumumab or placebo two weeks apart in addition to background methotrexate. Rescue treatment with nonbiologic disease modifying anti-rheumatic drugs (DMARDs) will be allowed from Week 16 in the double-blind period. All patients who complete the double-blind period without receiving rescue treatment will continue into the open-label period of the study. Re-treatment will be studied, starting at Week 24. Disease status will be measured every 4 weeks during the double-blind period and every 8 weeks during the open-label period.


OFA110634/GEN411 - Clinical efficacy and safety of ofatumumab in adult RA patients who have had an inadequate response to TNF-alpha antagonist therapy


A total of approximately 250 patients who had an inadequate response to TNF-alpha antagonist therapy will be enrolled. In the double-blind period, patients will be randomised to receive two 700 mg doses of ofatumumab or placebo two weeks apart in addition to background methotrexate. Rescue treatment with nonbiologic disease modifying anti-rheumatic drugs (DMARDs) will be allowed from Week 16 in the double-blind period. All patients who complete the double-blind period without rescue treatment will continue into the open-label period of the study. Re-treatment will be studied, starting at Week 24. Disease status will be measured every 4 weeks during the double-blind period and every 8 weeks during the open-label period.















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.


About Genmab A/S


Genmab is a leading international biotechnology company focused on developing fully human antibody therapeutics for unmet medical needs. Using unique, cutting-edge antibody technology, Genmab's world class discovery and development teams have created and developed an extensive pipeline of products for potential treatment of a variety of diseases including cancer and autoimmune disorders. As Genmab advances towards a commercial future, we remain committed to our primary goal of improving the lives of patients who are in urgent need of new treatment options. For more information on Genmab's products and technology, visit genmab.


GlaxoSmithKline Forward-Looking Statements


Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Business and Prospects in the company's Annual Report on Form 20-F for 2006.


Genmab Forward-Looking statements


This press release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with product discovery and development, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. Genmab is not under an obligation to up-date statements regarding the future following the publication of this release; nor to confirm such statements in relation to actual results, unless this is required by law.

Lubricant's Role In Keeping Joints Limber Comes Into Sharper Focus

Using a method that allows precise measurement of the biomechanical properties of the hip joints in mice, researchers at Duke University's Pratt School of Engineering have found new evidence that an ingredient of joint fluid called lubricin plays a significant role in keeping joints limber.



The researchers say the finding offers the strongest evidence yet that treatments designed to increase levels of lubricin in humans may help stall the deterioration of arthritic joints.



The team found that the arthritic joints of mice lacking the gene that controls the production of lubricin show greater friction than do joints in normal animals. When observed at the molecular level, the surface of the mutant animals' joint cartilage also appears rougher and less stiff -- a finding that the researchers said suggests a loss of the cartilage's mechanical integrity without lubricin.



"Lubricin has been considered important, but the experiments had not been done," said Stefan Zauscher, a professor of mechanical engineering and materials science at the Pratt School. "This is the first look at the effects on biomechanics of lubricin's presence or absence."



Team member Jeffrey Coles, a Ph.D. student working in Zauscher's laboratory, presented the findings at the annual meeting of the Orthopaedic Research Society, in San Diego. The work was supported by the National Institutes of Health.



While lubricin had been suspected to play a role in reducing joint friction, earlier studies had focused on another constituent of joint fluid called hyaluronic acid. Injections of this material are frequently used as a treatment for osteoarthritis, the most common form of arthritis. However, the treatment seems to work primarily as an anti-inflammatory agent, Zauscher noted, doing little to prevent further joint damage.



Last year, Zauscher's group reported evidence that lubricin acts as a repellant boundary layer between joint surfaces, reducing friction by preventing contacts altogether rather than simply "greasing the wheels" pratt.duke/news/index.php?story=260.



Those results stemmed from the first examination of the changing molecular forces between a model joint and glass slide as the amount of lubricin in the solution between them increased.



Now, the researchers have applied a similar technique to the molecular-level study of mouse joints, comparing normal mice to those lacking the gene for lubricin. They used an atomic force microscope (AFM) to examine the cartilage found on the surface of the ball at the top of the thigh bone that fits into the hip socket of the mice.



AFM microscopes have a sharp tip that scans the surfaces of structures at the level of individual atoms and measures the force of molecular-level interactions. In this case, the team chemically modified the tip to imitate the chemical properties of joint cartilage.



The researchers used the modified tips to probe the surface of normal and lubricin-deficient joints, gaining measurements of the amount of friction between the two surfaces. They also obtained measurements of the roughness and stiffness of the cartilage surface.



When compared with mice that have normal joint cartilage, mice lacking lubricin showed two to three times the amount of friction and their joint surfaces were more than twice as rough. The stiffness of the joint cartilage in mutant mice also was reduced by a factor of five, the researchers found. They noted that these findings are consistent with the significant tissue degeneration in early osteoarthritis.



"It's clear from our findings that lubricin is important for protecting the structural integrity of joints," Coles said.



The researchers next will examine the effects of replacing lubricin on the joint surfaces of mutant mice. They are seeking a better understanding of how lubricin carries out its role as a boundary lubricant, leading perhaps to an improved treatment option for osteoarthritis. Preliminary evidence suggests that lubricin injections may prevent, or at least slow, further deterioration of joint cartilage in the arthritic mice.






Collaborators on the study included Farshid Guilak of Duke University Medical Center and Duke's Pratt School of Engineering; J. Cha and Gregory Jay of Brown University; and Matthew Warman of Case Western Reserve School of Medicine.



Contact: Kendall Morgan


Duke University

Reverse Shoulder A Final Option For Restoring Function

Athough most artificial joints resemble the shape and structure of the joint they're designed to replace, one new prosthesis the reverse shoulder takes a different approach, reversing the position of the normal ball-and-socket design. The purpose of this anatomical flip-flop is to give you a shoulder that is stable enough to let you raise your arm, even if your rotator cuff is torn beyond repair, according to Cleveland Clinic's Arthritis Advisor.


"When we replace a shoulder joint, it's normally with a traditional, anatomically shaped design," says Joseph P. Iannotti, M.D., Ph.D., chairman of the department of orthopaedic surgery at Cleveland Clinic. "But this design only makes sense if the tears in your rotator cuff are repairable."


A working rotator cuff is the key to normal shoulder function since it's this group of four tendons encircling the shoulder that keeps the joint stable, holding the head of the humerous firmly against the curve of the scapula (glenoid cavity). Only when this head is stable can it act as an effective fulcrum, allowing the pull of your rotator cuff and deltoid muscles to raise your arm.


Loss of function


"As you age, it's not uncommon to develop a large tear in your rotator cuff," says Dr. Iannotti. "We often see tears in people in their 60s and 70s that may have been there for months or even years."


At some point, when a tear develops, the rotator cuff is unable to hold the humeral head within the socket, allowing it to slip out of place, hindering shoulder function. "Such tears can lead to pseudo or functional paralysis," says Dr. Iannotti. "Though your nerves are fully functional, you can no longer raise your arm to shoulder level."


If the tear is repairable, the shoulder muscles not too atrophied, and the shoulder has severe arthritis, your surgeon will likely recommend a traditional shoulder prosthesis whose design mimics the natural position of the humeral head (ball) and scapular depression (socket). This anatomic design is an effective solution as long as your repaired rotator cuff can provide adequate stability to the new joint.


"Some 20 to 30 percent of patients with significant rotator cuff tears and arthritis still have enough residual function to raise their arms to shoulder level before surgery, and are still good candidates for an anatomic prosthesis," says Dr. Iannotti.


Reverse-shoulder prerequisites However, if your tears are irreparable, the pain from arthritis is significant and, most importantly, you are unable to lift your arm to 90 degrees, then you may be a candidate for a reverse-shoulder procedure. Though the reverse shoulder prosthesis (made by DePuy, Tornier, Encore, and Zimmer) has been used clinically in Europe for more than two decades, it only received approval from the U.S. Food and Drug Administration in November 2004.















"Though I mostly recommend reverse shoulders for those over age 70, it can also make sense for younger patients who have a previous shoulder implant that has failed," says Dr. Iannotti, who has performed more than 120 of the procedures.


Candidates for a reverse shoulder must meet two other criteria good deltoid muscle function and a healthy glenoid bone. The importance of these is best explained by looking at the design of the reverse shoulder prosthesis.


Stable by design


As the name implies, the reverse shoulder flip-flops the normal position of the shoulder's ball and socket, putting a metal (titanium) stem topped with a plastic cup where the head of your humerus was and, on the other side, putting a metal plate and partial sphere (glenosphere) where the depression (glenoid cavity) on your scapula was. According to design engineers, this reversal changes the center of rotation within the joint, making the new head of the prosthesis inherently stable, regardless of the health of your rotator cuff.


With this design, good glenoid bone quality is a must because the bone must hold the screws which anchor the plate that holds the metal glenosphere. A functioning deltoid muscle is important since the new prosthesis depends upon this muscle for its arm-lifting power.


"As long as you have about 75 percent deltoid function, you'll be eligible for a reverse shoulder," says Dr. Iannotti.


Measured expectations


The range of motion you regain with a reverse shoulder will depend, in part, on how much function remains in your rotator cuff. "At a minimum, even with a little or no cuff function, you should be able to raise your arm to shoulder level," says Dr. Iannotti. "And those who retain at least partial function, especially in the posterior rotator cuff tendons, will often obtain 120 to 140 degrees of shoulder elevation."


Of course, getting to that point means a serious commitment to rehabilitation. The rehab program with a reverse shoulder is similar to that with an anatomic shoulder design, but it often can begin a bit sooner, since the shoulder's more innately stable design is less dependent on the health and healing of surrounding tissues.


Imperfect solution


Though a reverse shoulder can be a big help to certain people, it's far from an ideal solution. "The nature of the design puts a higher than normal load on the screws that are anchored into the glenoid process and, with repeated stress, can become loose and cause premature failure," explains Dr. Iannotti, who still views the reverse shoulder as a last-resort salvage solution in very selected patients.


"The reverse shoulder remains a complex procedure, for which there is not enough data to know long-term greater than 10-year results," says Dr. Iannotti. "What we do know is that, for a select group, it may be the best hope for more normal shoulder function."


Are You a Candidate?


If you experience or have one or more of the following, you may be eligible for a reverse shoulder procedure:


-- Severe shoulder arthritis with ongoing pain


-- Inability to raise extended arm to shoulder height


-- Irreperable large or massive rotator cuff tears


-- Healthy bone stock in scapula clavicle (glenoid cavity)


-- Functioning deltoid muscle


-- At least 65 years old, but younger if you've experienced failure of a previous shoulder replacement


Belvoir Media Group, LLC.

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Sarasota, FL 34231

United States

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Using Statins To Potentially Treat Rheumatoid Arthritis

Study finds statins have beneficial effect on rheumatoid arthritis cells in vitro
Statins, a class of drugs widely used to treat high cholesterol, have also recently been studied for their potential role in inflammation and other cell processes, including immune response. They have also been shown to induce apoptosis (cell death) in normal cells and tumor cells. Rheumatoid arthritis (RA) causes proliferation of synovial tissue, which lines the joints, but little is known about the effect of statins on this type of tissue. A study published in the February 2006 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis) examined whether statins are able to induce apoptosis in synovial cells of patients with RA and found that they have potential as a novel way of treating the disease.



The activation and proliferation of synovial cells, which is thought to play a key role in RA, may be exacerbated when apoptosis of synovial cells is either insufficient or resistant to treatment. In the first study to demonstrate whether statins can induce apoptosis in synovial cells of RA patients, researchers led by Takao Nagashima of Jichi Medical School, Tochigi, Japan measured the effect in vitro of two statins, fluvastatin (a fat-soluble statin) and pravastatin (a water-soluble statin) on human synovial cells from patients with RA and osteoarthropathy. "In the present study, we demonstrated that fluvastatin induced apoptosis in synoviocytes from patients with RA, but not in those from patients with osteoarthropathy, suggesting that the apoptotic effect of fluvastatin is a mechanism for suppression of inflammatory arthritis such as RA by statins," the authors state.



They were also able to determine the pathway by which apoptosis occurred: the inhibition of protein geranygeranylation (a process involving the metabolism of certain proteins that is essential for proper cell function, including the survival of vascular smooth muscle cells) was shown to be necessary for apoptosis to occur in these cells. Specifically, the pathway involves inhibition of the geranylgeranylated protein RhoA/RhoA kinase, which has already been shown to be involved in apoptosis.



The researchers point out that the in vitro concentrations they used of the statins were much higher than amounts that would normally be prescribed to patients. Although they note that it is possible that in the human body relatively low, but sustained, blood levels of statins would exert an effect similar to that seen in vitro with higher concentrations and short incubation times, they acknowledge that the therapeutic effect of fluvastatins in patients remains to be determined.



The authors conclude: 'The induction of apoptosis in RA synovial cells by fluvastatin and the biologic antiatherosclerotic properties of the statins suggest that they may turn out to be ideal therapeutic agents in RA. Based on these results, we propose that the statins warrant clinical trials as potential modifiers of RA."







Article: "Apoptosis of Rheumatoid Synovial Cells by Statins Through the Blocking of Protein Geranlgeranylation," Takao Nagashima, Hitoaki Okazaki, Kazuo Yudoh, Hiroaki Matsuno, Seiji Minota, Arthritis & Rheumatism, February 2006; 54:2; pp. 579-586.



Contact: Amy Molnar

amolnarwiley

John Wiley & Sons, Inc./

CEL-SCI Study Shows CEL-2000 Vaccine Blocks Progression Of Rheumatoid Arthritis

CEL-SCI Corporation (NYSE CVM) and their scientific collaborators announced that the Company's CEL-2000 vaccine demonstrated that it is able to block the progression of rheumatoid arthritis (RA) in a mouse model. The results were published in the scientific peer-reviewed Journal of International Immunopharmacology (online edition) in an article titled "CEL-2000: A Therapeutic Vaccine for Rheumatoid Arthritis Arrests Disease Development and Alters Serum Cytokine / Chemokine Patterns in the Bovine Collagen Type II Induced Arthritis in the DBA Mouse Model" with lead author Dr. Daniel Zimmerman. The study was co-authored by scientists from CEL-SCI, Washington Biotech, Northeastern Ohio Universities Colleges of Medicine and Pharmacy (NEOUCOMP) and Boulder BioPath.


CEL-2000, administered after disease (RA) symptoms had started, prevented, in a statistically significant manner, the further development of arthritic conditions, including joint swelling and deformation, bone and cartilage changes and was accompanied by serum cytokine alterations over the CEL-2000 treatment period with comparable or better activity than the well accepted etanercept (Enbrel®) therapy. The mode of action is very consistent with the findings of induction of IL-12 followed by interferon gamma and an inhibition of TNF-alpha and IL-17 production. TNF-alpha and IL-17 are both key cytokines for induction of the pathology seen in rheumatoid arthritis and TNF-alpha is the target of many current RA therapies such as Enbrel, Remicaid, and Humaria. The protection effect mediated by CEL-2000 treatment against RA was also demonstrated histologically with significant reductions in: 1) inflammation, 2) cartilage destruction, 3) bone resorption, and 4) pannus membrane formation in the synovial space compared to untreated controls.


Geert Kersten, Chief Executive Officer of CEL-SCI said, "These experimental results were achieved through a reduction of the inflammatory response that is known to attack the patients' joints. The mode of action of CEL-2000 in RA appears to be similar to our new investigational therapy for H1N1 hospitalized patients, as it attempts to avoid the excess TNF-alpha and other pro-inflammatory cytokines. We feel that this new data is encouraging both for this rheumatoid arthritis vaccine as well as in support of our H1N1 treatment currently under development."


In these studies, mice were injected with collagen to induce the autoimmune (RA) disease. Therapy with Enbrel or CEL-2000 was initiated after disease (RA) symptoms have been established and treatment continued for 28 days after the initiation of a significant, uniform, and measurable level of arthritic disease in groups of mice. CEL-2000 was administered only twice, however Enbrel had to be administered every other day for the 28 day study period (as indicated for Enbrel use). The extent of disease, as measured by deformation of foot joints (Arthritic Index (AI) score), of untreated animals and any improvements resulting from CEL-2000 and Enbrel treated animal were then compared. In another study, CEL-2000 was administered 5 times over a 70 day period and the animals were monitored for a total study period of 90 days. In each case, CEL-2000 treatment proved effective in blocking progression of disease (RA) with statistically significant reduction in AI score compared to controls. The CEL-2000 treatment was deemed safe and well tolerated without any reported adverse effects related to treatment.















The CEL-2000 treatment appeared to change the course of the immune response in the diseased (RA) animals, limiting the development of the destructive action of Th17 and tumor necrosis factor alpha (TNF-alpha). Analysis of serum levels of 21 cytokines/chemokines after 10 days of CEL-2000 treatment indicated reductions in the characteristic cytokine markers of rheumatoid arthritis, TNF-alpha and IL-17, as well as IL-6, and MCP-1. A number of cytokine changes were also seen with Enbrel treatment, but to a lesser degree than that seen with CEL-2000 treatment.


CEL-2000 may also offer a number of potential advantages over existing rheumatoid arthritis treatments, such as Enbrel. Data collected in the animal studies conducted with CEL-2000 demonstrated that CEL-2000 is an effective treatment against rheumatoid arthritis even with administration of many fewer treatments than for example Enbrel. CEL-2000 is also potentially a more disease-type specific therapy, should be significantly less expensive to manufacture, and finally, CEL-2000 could also be useful for patients who are not able to take or who may be unresponsive to other existing anti-arthritis therapies.


This research featured the multidisciplinary team of collaborators bringing to the project expertise of several different animal models of arthritis (Washington Biotech), long time association with modern molecular therapies and evaluation for RA (Bolder Biopath), experience with other LEAPS immunogens, and experience and expertise studying cytokines and with mechanistic studies of the LEAPS technology (NEOUCOMP), and peptide technologies (21st Century Biochemicals) to complement the expertise of the CEL-SCI researchers.


Rheumatoid arthritis treatments comprise an approximately $13 billion market. Enbrel, a leading rheumatoid arthritis treatment sold by Amgen and Wyeth, reported US sales in 2007 of about $3.2 billion. Enbrel is a soluble recombinant protein of a human TNF-alpha receptor linked to human IgG Fc. In some cases, human or humanized monoclonal antibodies specific against TNF-alpha have also been used for therapy in rheumatoid arthritis. These therapies remove or inactivate TNF-alpha, a natural human cytokine required in many immune functions for normal defenses.


CEL-SCI's rheumatoid arthritis vaccine CEL-2000 was discovered as part of work with the Company's ongoing research and development activities with its L.E.A.P.S.™ (Ligand Epitope Antigen Presentation System) technology. L.E.A.P.S. is a novel T-cell modulation platform technology that enables CEL-SCI to design and synthesize proprietary immunogens. Any disease for which an antigenic sequence has been identified, such as infectious, parasitic, malignant or autoimmune diseases and allergies, are potential therapeutic or preventive sites for the application of L.E.A.P.S. technology.


The concept behind the L.E.A.P.S. technology is to directly mimic cell-cell interactions and activate immune cells with synthetic peptides. The L.E.A.P.S. constructs containing the antigenic disease epitope linked to a immune-cell binding ligand (ICBL) can be manufactured by peptide synthesis or by covalently linking the two peptides. Depending upon the type of L.E.A.P.S. construct and ICBL used, CEL-SCI is able to direct the outcome of the immune response towards the development of T-cell function with primarily effector T-cell functions (T Lymphocyte; helper/effector T lymphocyte, type 1 or 2 [Th1 or Th2], cytotoxic [Tc] or suppressor [Ts]). Therefore, it would appear that the L.E.A.P.S. construct represents a chimeric peptide with bi-functional behavior.


About CEL-SCI Corporation


CEL-SCI Corporation is developing products that empower immune defenses. Its lead product Multikine is being readied for a global Phase III trial in advanced primary head and neck cancer. CEL-SCI is also developing an immunotherapy (LEAPS-H1N1-DC) to treat H1N1 hospitalized patients and a vaccine (CEL-2000) for Rheumatoid Arthritis using its L.E.A.P.S. technology platform. The LEAPS-H1N1-DC treatment involves non-changing regions of H1N1 Pandemic Flu, Avian Flu (H5N1), and the Spanish Flu as CEL-SCI scientists are very concerned about the creation of a new more virulent hybrid virus through the combination of H1N1 and Avian Flu, or maybe Spanish Flu. This investigational treatment is currently being tested in a clinical study at Johns Hopkins University. The Company has operations in Vienna, Virginia, and in/near Baltimore, Maryland.


When used in this report, the words "intends," "believes," "anticipated" and "expects" and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, lack of regulatory clearance to proceed with clinical trials, an inability to duplicate the clinical results demonstrated in clinical studies that have been completed or that are initiated in the future, timely development of any potential products that can be shown to be safe and effective, unwillingness of regulatory authorities to engage in further regulatory dialogue, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital, and the risk factors set forth from time to time in CEL-SCI Corporation's SEC filings, including but not limited to its report on Form 10- K for the year ended September 30, 2009. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


Source: CEL-SCI Corporation


View drug information on Enbrel.

MabThera for moderate-severe rheumatoid arthritis, good study results

Roche together with development partners Genentech and Biogen Idec announced today that a Phase IIb clinical study of
MabThera/Rituxan (rituximab) met its primary endpoint of a greater proportion of MabThera-treated patients achieving an
American College of Rheumatology (ACR) 20 response at week 24, compared to placebo, in patients who were also treated with
methotrexate (MTX). In this study, patients with moderate-to-severe rheumatoid arthritis (RA) who received two infusions of
MabThera over a two-week period in combination with a stable dose of MTX experienced improved symptoms compared to patients
who received placebo and MTX. The benefit in the MabThera/Rituxan treated patients was present regardless of whether
additional corticosteroids were administered.


"The preliminary data from this latest study in rheumatoid arthritis confirms MabThera as a promising alternative to current
therapies available to patients with RA and are consistent with earlier data showing efficacy and safety of MabThera. As we
continue to explore and evaluate MabThera as a potential treatment for RA, we look forward to the results of ongoing analyses
which will be presented next year", commented Dr. Eduard Holdener, Head of Global Pharma Development, Roche.


This Phase IIb study, DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of
Rituximab in RA), was designed to evaluate the efficacy and safety of varying doses of MabThera/Rituxan in combination
with methotrexate in patients with active RA who currently have an inadequate response to methotrexate. The influence of a
short initial course of corticosteroids was also evaluated.


All regimens in the study were generally well tolerated. The reported rate of serious adverse events was not significantly
different than seen in previous studies of MabThera/Rituxan in RA. MabThera/Rituxan is also being studied in an additional
ongoing trial, REFLEX (Randomised Evaluation oF Long-term Efficacy rituXimab in RA)
in patients who have an inadequate response to anti-TNF alpha (tumour necrosis factor) therapies.


MabThera/Rituxan is a therapeutic antibody that selectively depletes B cells, which may play a key role in the inflammatory
cascade of RA. B cells are an important element in the immune system, helping the body to fight off infection. However in
autoimmune diseases like RA, the immune system acts abnormally leading to an attack on normal healthy tissue such as the
joints.


By depleting B cells, which are believed to be involved in maintaining the attack on healthy tissue, MabThera/Rituxan is
thought to break the cycle of rheumatoid arthritis disease. MabThera/Rituxan is already proven effective in RA following a
single course of therapy1,2.


There is a large unmet clinical need for RA treatments. Only around 50 percent of patients respond to and maintain treatment
with DMARD (disease modifying anti-rheumatic drugs) therapy long term. Data from existing clinical trials indicates that
MabThera/Rituxan is safe and well-tolerated in people with RA.















About the Study


DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of R in RA) is a
Phase IIb study evaluating the efficacy and safety of varying doses of MabThera/Rituxan and corticosteroids in combination
with a fixed dose of methotrexate in patients who have failed at least one disease-modifying anti-rheumatic drug (DMARD) and
are inadequately responding to methotrexate. A total of 465 patients from the United States, Canada, Europe, and Australia
were randomised in this multi-centre, randomised, double-blind, placebo-controlled study. DANCER included three different
dosages of MabThera/Rituxan (placebo; 2x500mg; 2x1000mg) and corticosteroid (placebo; i.v. 200mg; and i.v. 200mg + p.o.
570mg).


About MabThera/Rituxan


Unlike current RA treatments, MabThera/Rituxan is a therapeutic monoclonal antibody that selectively targets B cells, which
are believed to play a key role in the inflammatory cascade of the disease. By doing so, MabThera/Rituxan aims to break the
inflammatory cascade of RA - a series of reactions inflaming the synovia and leading to the cartilage loss and bone erosion
that is characteristic of the disease in which B cells are thought to play a key role. MabThera/Rituxan has been used for
over 7 years for the treatment of a form of lymphatic cancer called non-Hodgkin's lymphoma (NHL) with over 380,000 patients
treated to date.


About Rheumatoid Arthritis


Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining
in joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately
leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain, and movement
limitation around joints of the hands, feet, elbows, knees and neck. In more severe cases of RA the eyes, lungs or blood
vessels may be involved. RA may also shorten life expectancy by affecting major organ systems and after 10 years, less than
50% of patients can continue to work or function normally on a day to day basis. RA is one of the most common forms of
autoimmune disease and affects more than 6 million people worldwide, up to 2 million of whom are in Europe.


ACR improvements


The ACR response is a standard assessment used to measure patients' responses to anti-rheumatic therapies, devised by the
American College of Rheumatology (ACR). It requires a patient to have a defined percentage reduction in a number of symptoms
and measures of their disease. For example, a 20 or 50 percent level of reduction (the percentage of reduction of RA
symptoms) is represented as ACR20, ACR50. ACR 20 indicates a 20 percent improvement in the number of swollen and tender
joints, as well as a 20 percent improvement in three of five categories: patient assessment, physician assessment, pain
scale, Health Assessment Questionnaire, and acute phase reactant (erythrocyte sedimentation rate or c-reactive protein) ACR50
response is exceptional for existing treatments and represents a significant improvement in a patient's condition. A 'Major
Clinical Response' is defined as a continuous ACR 70 maintained for at least 6 months.


About Roche


Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core
businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention,
diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality
of life. Roche is number one in the global diagnostics market, the leading supplier of medicines for cancer and
transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in
prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly
65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority
ownership interests in Genentech and Chugai.


About Genentech


Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for
significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or
are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the
United States and licenses several additional products to other companies. The company has headquarters in South San
Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional
information about the company, please visit gene.


About Biogen Idec


Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing,
and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare.
For product labelling, press releases and additional information about the company, please visit biogenidec.



All trademarks used or mentioned in this release are legally protected.


References:


1. Edwards J et al. Efficacy of B-cell targeted therapy with rituximab in patients with rheumatoid arthritis. New England
Journal of Medicine 2004;350:2572-81

2. Emery P et al. Efficacy and safety of rituximab at 2 years following a single treatment in patients with active arthritis.
Oral presentation ACR 2004.

Access To Psychological Support And Self-Management Courses Could Ease The Emotional Burden Of Arthritis/Rheumatism, Survey Says

An online survey for World Arthritis Day (WAD), completed by over 3,600* respondents revealed that access to psychological support and self-management courses could help people with arthritis/rheumatism cope more effectively with their condition and achieve better quality of life. Healthcare professionals, people with rheumatic disease and their carers, who responded to the survey, highlight the importance of integrating psychological support into the standard treatment regime.



The survey, a project run by the European League Against Rheumatism (EULAR) Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), was completed by people with arthritis/rheumatism, their carers and health professionals from over 50 countries across the world.



Ninety seven percent of people with rheumatism/arthritis and carers indicated that this condition affects them/people they care for emotionally and 5% of them said it may lead to depression. Despite of the scale of the problem only 35% of the survey respondents said they raise the emotional impact of their arthritis/rheumatism with their doctor.



Clinical data demonstrates that the quality of life of these people can be enhanced by introducing special coping strategies1. The majority of people with arthritis/rheumatism who responded to the survey saw the need for professional support: 85% emphasised that psychological support (psychotherapy, sessions with psychologists, treatments) should be included in the overall care and over a half of them would like to have access to self-management courses.



Similarly, health professionals are increasingly aware of the psychological impact of arthritis/rheumatism: 71% said they bring this problem up during a consultation, 33% said they refer their patients to the specialist treatment (e.g. psychotherapy) and 22% suggest a self-management course, if one exists in the given country.



"The main message coming out of the World Arthritis Day survey is the real need for a holistic approach in treating people with arthritis and rheumatism, ensuring the treatment paradigm covers all aspects of these conditions and not just the physical symptoms. This is clearly voiced by both patients and physicians and needs to be recognized and addressed within the structure of national healthcare systems" - said president of EULAR Executive Committee, Prof. Ferdinand C. Breedveld.



"Our survey clearly demonstrates that both people with arthritis/rheumatism and healthcare professionals recognize the importance of addressing psychological aspects of this condition. Yet, in many countries support is not available or limited. - said Sandra Canadelo, Chairperson of the Standing Committee of People with Arthritis/Rheumatism in Europe (EULAR) - This year, on World Arthritis Day, we hope that our call for better access to different forms of psychological support for people with arthritis/rheumatism will be heard by health policy makers on a national and international level."
















The findings from the Think Positive survey correspond with the available clinical evidence. This evidence demonstrates that arthritis/rheumatism can have a debilitating effect on people's lives by restricting physical, psychological and social function. A half to two thirds of people with arthritis/rheumatism report lost social relationships, disrupted leisure activities and limitations in employment because of psychological problems2. In many cases some types of arthritis/rheumatism can be associated with depression and anxiety3.







Results from the Think Positive survey are reflected in the individual stories of people with arthritis/rheumatism who share personal experiences of coping with their conditions emotionally and finding the best way to a keep positive frame of mind. Their testimonials are available on WAD website worldarthritisday/



About the WAD survey



The World Arthritis Day survey is a project run by EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE). Every year the survey looks at different aspects of arthritis/rheumatism and generates useful statistics to support a call for better standards of treatment and care for people with arthritis/rheumatism. The "Think Positive" theme acknowledges the emotional impact of this condition and the need for better psychological support being offered to people with rheumatism/arthritis.



About self-management courses



Self-management courses are run by people with arthritis/rheumatism who have been especially trained to teach techniques which help people get greater control over their disease, increase their confidence and improve their quality of life. These sessions create forums during which people feel comfortable to share their experiences and learn from each other. They enhance dialog and relationship building with other people affected by arthritis/rheumatism.



About EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE)



The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations. EULAR endeavours to stimulate, promote, and support the research, prevention, treatment and rehabilitation of rheumatic diseases.



The national organisations of people with arthritis/rheumatism across Europe work together via the EULAR Standing Committee of PARE. The EULAR Standing Committee of PARE brings together representatives of arthritis and other musculoskeletal user groups around Europe to work towards improving the quality of life for the more than 100 million people in Europe living with these conditions. The committee's vision is of people with arthritis and other musculoskeletal conditions in Europe being empowered to lead full and independent lives.



More information is available on the website worldarthritisday/ and eular/



References:



1 Covic T et al, The impact of passive coping on rheumatoid, Rheumatology 2000; 39: 1027 1030


2 Ryan S, The Psychological and Social Implications of Rheumatoid Arthritis, available at NHS library: library.nhs.uk/musculoskeletal/viewresource.aspx?resid=5218 accessed on 22.08.08


3 Abdel-Nasser et al, Depression and depressive symptoms in rheumatoid arthritis patients: an analysis of their occurrence and determinants, Rheumatology, Volume 37, Number 4, April 1998 , pp. 391-397(7)



Acknowledgement



The WAD 'Think Positive' survey is supported by an educational grant from Pfizer



Source: Birte Gl??esing


Ruder Finn Public Relations

Expanded Indications, Novel Targets Driving Activity In Autoimmune Disease Therapeutics

Already a major
therapeutic disease sector accounting for drug sales in excess of $18
billion worldwide, the incidence of autoimmune disease in developed
countries is increasing. The impact of autoimmunity on patient
quality-of-life is well known, but it has only been in the last ten
years with the introduction of biological drugs capable of modulating
the immune cascade that effective therapies for this most intractable
family of diseases have become available. The result has been a drug
sector that has grown rapidly to include more than a half-dozen
products with annual sales exceeding $1 billion.



The past few years have been marked by expanded indications, creating
new treatment options for caregivers and their patients. But in spite
of these recent successes -- and in part because of them -- work to
identify and develop new therapeutic candidates has intensified.



As with virtually any drug with significant efficacy, side effects
remain a major issue. Much of the current wave of development
activity is focused on the search for new classes of autoimmune drugs
that achieve a therapeutic benefit with minimal side effects. These
approaches include drug candidates that target specific immune
response processes, such as inhibiting the action of adhesion
molecules or interfering with the migration of activated immune cells
from lymph nodes.



Arthritis, because of its market size and economic importance, is
often the therapeutic target for pipeline therapies in this sector,
while less prevalent disease segments benefit almost exclusively
through secondary or expanded indications. The outlook for the
psoriasis segment is closely linked to the commercial market for
arthritis treatment, due to the significant prevalence of psoriasis
patients to suffer from psoriatic arthritis.



The Greystone research study 'Autoimmune Disease Therapeutics'
analyzes approved and development-stage therapeutic drugs for six
major autoimmune disease segments, and includes forecasts, analysis,
descriptions and evaluations of current and probable future market
developments, technology issues, and business factors.



More information is available
here.



About Greystone



Greystone Associates is a medical and healthcare technology
consulting firm providing services in strategic planning, venture
development, product commercialization, and technology and market
assessment.


Greystone Associates

Cost Shifting May Make Arthritis Medications Too Expensive For Medicare Beneficiaries

Biologic disease-modifying antirheumatic drugs (DMARDs) such as adalimumab, etanercept and infliximab are effective at reducing symptoms and slowing progression of rheumatoid arthritis (RA). These drugs act more quickly, require less laboratory monitoring, and are better tolerated than nonbiologic DMARDs, but they are also up to 100 times more expensive. Insurance plans differ greatly in their coverage of and cost sharing for biologic DMARDs, sometimes shifting a large portion of the cost of patients. A new study examined the cost-sharing structures for biologic DMARDs in Part D plans and the resulting cost burden to patients. The study was published in the June issue of Arthritis Care & Research.



In 2003, Congress created the Medicare Replacement Drug Demonstration (MRDD) to provide temporary drug insurance until the start of Medicare Part D in 2006. The MRDD, which ran September 2004 - December 2005, targeted low-income vulnerable Medicare patients with select conditions, including RA, who did not have comprehensive drug insurance coverage. This program had similar cost-sharing arrangements to Medicare Part D and evaluations showed that it reduced financial barriers and improved health outcomes. However, unlike the MRDD, Part D plans could place high-cost items such as biologic DMARDs in a specialty tier, where they are subject to higher patient cost sharing. There is concern that specialty tiering imposes a heavy financial burden on RA patients.



Led by Jennifer M. Polinski of Brigham and Women's Hospital in Boston, researchers followed almost 15,000 vulnerable, low-income patients who were enrolled in the MRDD as they transitioned into Part D in 2006. They grouped patients into one of three drug coverage options: enrollment in a Part D plan further stratified by a Medicare Advantage or stand-alone plan, other creditable coverage or unknown coverage. They examined the benefit design of each plan, as well as potential differences in beneficiaries' annual out-of-pocket costs for biologic DMARDs under three coverage scenarios.



They found that 81 percent of poor and disabled Medicare beneficiaries with RA who participated in the MRDD program had enrolled in Part D plans by July 2006. Compared with stand-alone Part D plans, Medicare Advantage plans offered lower deductibles, lower premiums, and were more likely to require copayments (which are fixed), rather than coinsurance (typically a percentage paid by the insured person pays after an insurance deductible has been exceeded). They also placed significantly fewer restrictions on biologic DMARD reimbursement. "In spite of the greater generosity and lesser restrictions of Medicare Advantage plans, the most sick and most financially needy patients enrolled in these plans less often than they did in stand-alone plans," the authors note.
















Most patients enrolled in plans that placed biologic DMARDs on high-cost specialty tiers and used coinsurance proportions as high as 75 percent. The specialty tier was created to ensure that beneficiaries receiving high-cost biologic agents were not discriminated against in terms of cost sharing, but there is concern about the financial impact of this structure, especially the widespread use of high coinsurance. The study found that Part D plans that require coinsurance instead of copayments shift the financial burden of these high-cost medications from the plan to the patient and to Medicare. In plans where cost sharing is high (e.g. plans with high coinsurance), patients may delay or not even begin therapy due to the high cost; in plans with cost sharing that is steep but manageable (e.g. plans with high copayments) patients may begin therapy but then discontinue it when faced with paying the full cost of the medication out of pocket. "Neither scenario is optimal for patients who may benefit from biologic DMARDs," the authors point out.



Specialty tier and coinsurance resulted in estimated annual expenditures for patients that exceeded $4,000 despite drug insurance coverage and more Part D plans have adopted specialty tiering over time. In 2006, 60 percent of the national stand-alone plans used this system but by 2008, 87 percent were using it. Similarly, between 2006 and 2008 the number of plans charging 33 percent coinsurance increased more than five-fold. "Patients assume up to 28 percent and Medicare assumes more than 58 percent of the costs of biologic DMARDs in our scenarios, yet neither is in a position to sustain such financial burden," the authors conclude. "As more biologic DMARDs are approved and used for RA and more plans use the specialty tier system, both beneficiaries and Medicare face costs they may be increasingly unable to afford."



Article: "Impact of Medicare Part D on Access to and Cost Sharing for Specialty Biologic Medications for Beneficiaries with Rheumatoid Arthritis," Jennifer M. Polinski, Penny E. Mohr, Lorraine Johnson, Arthritis & Rheumatism (Arthritis Care & Research), June 2009.



Source:
Sean Wagner


Wiley-Blackwell