Endo Licenses U.S. Rights For Voltaren(R) Gel — The First FDA-Approved Topical Treatment For Relief Of Osteoarthritis Pain
March 6, 2008
Endo Pharmaceuticals Inc., a wholly owned subsidiary of Endo Pharmaceuticals Holdings Inc. (NASDAQ: ENDP) and a market leader in pain management, announced that it has entered into a licensing agreement with Novartis to obtain the exclusive U.S. marketing rights for the prescription medicine Voltaren® Gel (diclofenac sodium topical gel) 1%.
Voltaren Gel received regulatory approval in October 2007 from the U.S. Food and Drug Administration, becoming the first topical prescription treatment for use in treating pain associated with osteoarthritis and the first new product approved in the U.S. for osteoarthritis since 2001. Voltaren Gel has been granted marketing exclusivity in the U.S. as a prescription medicine until at least October 2010.
Voltaren Gel, which is a nonsteroidal anti-inflammatory (NSAID) medication, is indicated for use in treating pain associated with osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Osteoarthritis is a chronic, painful condition characterized by the breakdown of cartilage in the joint, often leading to working limitations and reduced overall health.
Clinical trials have demonstrated Voltaren Gel to be highly effective in treating osteoarthritis pain in the hands and knees, which are the body’s most commonly affected joints. Voltaren Gel delivers effective pain relief with a favorable safety profile as its systemic absorption is on average 6% of the systemic exposure from a comparable dose of an oral form of diclofenac sodium.
“Voltaren Gel is an ideal strategic and commercial fit for Endo. It is an approved product that we plan to launch in the U.S. as soon as possible,” said Nancy J. Wysenski, Chief Operating Officer of Endo Pharmaceuticals. “We believe it will further enhance our leadership position in pain management by extending our reach into the mild-to-moderate segment of the osteoarthritis pain market while adding growth and diversification to our revenue base. In addition, Voltaren Gel will allow us to leverage our established expertise in marketing topical pain therapies. As a result, we expect market availability and momentum behind Voltaren Gel to build rapidly and provide broader access to patients in the U.S. suffering from pain associated with osteoarthritis.”
Voltaren Gel will compete in the emerging topical NSAID market, which is expected to grow given the aging U.S. population. Of the estimated 84 million NSAID and Cox-II prescriptions written annually in the U.S., about 40% are osteoarthritis-related. The dollar value of this market is approximately $3.3 billion, with roughly half of the value coming from NSAIDs and the remainder from Cox-IIs. Endo estimates U.S. peak annual sales for Voltaren Gel in treating osteoarthritis pain in the range of $250-300 million.
Endo expects to commercialize Voltaren® Gel without delay, initially using one of its two specialty sales forces, consisting of 160 representatives, prior to executing a full physician launch in late May with an additional 275 contract sales representatives targeting primary care physicians who prescribe NSAIDs and Cox-IIs.
Under the terms of the five-year agreement with Novartis, Endo will make an upfront cash payment of $85 million. Novartis is also eligible to receive a one-time milestone payment of $25 million if annual sales exceed $300 million. Novartis will receive royalties on the net sales of Voltaren Gel in the U.S. and will supply this product to Endo.
As a result of today’s announcement, Endo is revising its guidance for 2008. Net sales are now projected to be between $1.245 billion and $1.280 billion, up from the previous projections of $1.225 billion to $1.250 billion. Adjusted diluted earnings per share (excluding estimated milestone payments to partners and the expensing of stock-based compensation charges) for 2008 are now expected to be between $2.03 and $2.07, down from the prior adjusted diluted EPS guidance of $2.18 to $2.22. The change in EPS guidance reflects the impact of the additional field force, expected launch costs and amortization of the upfront payment associated with Voltaren Gel. Expectations are that Voltaren Gel will begin to be accretive to earnings in 2009, according to Charles A. Rowland, Jr., Chief Financial Officer.
The efficacy and safety of Voltaren Gel were studied in more than 900 patients with knee or hand osteoarthritis. The U.S. approval was based on several studies, including the results of two randomized, double-blind, placebo-controlled efficacy studies and a 12-month safety study. Voltaren Gel was shown to significantly reduce pain in hand and knee osteoarthritis, with pain relief sustained through the end of treatment. After six weeks of treatment in an efficacy study of patients with osteoarthritis of the hand, results showed that pain levels were reduced by nearly half (46%). In a 12-week study in patients with osteoarthritis of the knee, Voltaren Gel demonstrated a 51% reduction in pain.
Approximately 21 million people in the U.S. have osteoarthritis, [1] and the aging population in the U.S. means 72 million more may be at risk for developing the condition by 2030. [2]
About Osteoarthritis
Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint. Cartilage cushions the ends of the bones in joints — such as knees, hands, elbows, wrists, ankles and feet — which allows for easy movement. When cartilage erodes, bones can rub together, resulting in pain and loss of free movement in the joint. [3] The most common symptoms include pain, joint soreness, stiffness and deterioration of overall coordination, posture and walking.
Osteoarthritis is the leading cause of disability in the U.S., and the overall patient population for osteoarthritis and chronic joint pain is comparable in size to that of hypertension. Arthritis and related conditions, such as osteoarthritis, cost the U.S. economy nearly $128 billion per year in medical care and indirect expenses, including lost wages and production. [4] Despite the high prevalence of osteoarthritis, there is no cure for this disease, which tends to progressively reduce mobility and the overall health state in the affected patients.
About Voltaren® Gel
Voltaren Gel provides 1% diclofenac sodium in a topical gel formulation. It is a non-steroidal anti-inflammatory (NSAID) medication indicated for the pain of osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Voltaren Gel delivers highly effective pain relief with a favorable safety profile. The amount of diclofenac sodium that is systemically absorbed from Voltaren Gel is on average 6% of the systemic exposure from a comparable dose of an oral form of diclofenac sodium.
Important Safety Information
The most common adverse reactions reported in Voltaren® Gel clinical trials were application site reactions in 7% of treated patients. With all NSAIDs there may be an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. The use of Voltaren Gel is contraindicated in patients with a known hypersensitivity to diclofenac. Voltaren Gel should not be administered to patients who have experienced asthma, urticaria or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. Voltaren Gel is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Voltaren Gel should not be used in combination with other oral NSAIDs or aspirin because of the potential for increased adverse effects. Similarly, combined use of Voltaren Gel with other topical products, such as sunscreens and cosmetics, on the same skin area has not been tested and should be avoided because of the potential to alter local tolerability and absorption.
About Endo
Endo Pharmaceuticals Holdings Inc. is a specialty pharmaceutical company with market leadership in pain management. Through its wholly owned Endo Pharmaceuticals Inc. subsidiary, the company is engaged in the research, development, sale and marketing of branded and generic prescription pharmaceuticals used primarily to treat and manage pain. More information, including this and past press releases of Endo Pharmaceuticals Holdings Inc., is available at http://www.endo.com.
Forward-Looking Statements
This press release contains information that includes or is based on “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act. These statements, including estimates of future net sales, future expenses, future net income and future earnings per share, are subject to risks and uncertainties. Forward-looking statements include the information concerning the company’s possible or assumed results of operations. Also, statements including words such as “believes,” “expects,” “anticipates,” “intends,” “estimates,” “plan,” “will,” “may” or similar expressions are forward-looking statements. Endo has based these forward-looking statements on its current expectations and projections about the growth of its business, its financial performance and the development of its industry. Because these statements reflect Endo’s current views concerning future events, these forward-looking statements involve risks and uncertainties. Investors should note that many factors could affect Endo’s future financial results and could cause its actual results to differ materially from those expressed in forward-looking statements contained in this press release. Important factors that could cause its actual results to differ materially from the expectations reflected in the forward-looking statements in this press release include, but are not limited to: its ability to successfully develop, commercialize and market new products; timing and results of pre-clinical or clinical trials on new products; its ability to obtain regulatory approval of any of its pipeline products; competition for the business of its branded and generic products, and in connection with its acquisition of rights to intellectual property assets; market acceptance of its future products; government regulation of the pharmaceutical industry; its dependence on a small number of products; its dependence on outside manufacturers for the manufacture of its products; its dependence on third parties to supply raw materials and to provide services for certain core aspects of its business; new regulatory action or lawsuits relating to its use of narcotics in most of its core products; its exposure to product liability claims and product recalls and the possibility that the company may not be able to adequately insure itself; its ability to protect its proprietary technology; the successful efforts of manufacturers of branded pharmaceuticals to use litigation and legislative and regulatory efforts to limit the use of generics and certain other products; its ability to successfully implement its acquisition and in-licensing strategy; regulatory or other limits on the availability of controlled substances that constitute the active ingredients of some of its products and products in development; the availability of third-party reimbursement for its products; the outcome of any pending or future litigation or claims by the government; its dependence on sales to a limited number of large pharmacy chains and wholesale drug distributors for a large portion of its total net sales; significant litigation expenses to defend or assert patent infringement claims; any interruption or failure by its suppliers, distributors and collaboration partners to meet their obligations pursuant to various agreements with Endo; a determination by a regulatory agency that Endo is engaging in inappropriate sales or marketing activities, including promoting the “off-label” use of its products; existing suppliers become unavailable or lose their regulatory status as an approved source, causing an inability to obtain required components, raw materials or products on a timely basis or at commercially reasonable prices; the loss of branded product exclusivity periods and related intellectual property; and its exposure to securities that are subject to market risk.
The company does not undertake any obligation to update its forward-looking statements after the date of this Report for any reason, even if new information becomes available or other events occur in the future. You are advised, however, to consult any further disclosures we make on related subjects in our 10-K, 10-Q and 8-K reports to the Securities and Exchange Commission (or SEC). Also note that Endo provides the preceding cautionary discussion of risks, uncertainties and possibly inaccurate assumptions relevant to its business. These are factors that, individually or in the aggregate, the company believes could cause its actual results to differ materially from expected and historical results. Endo notes these factors for investors as permitted by the Private Securities Litigation Reform Act of 1995. You should understand that it is not possible to predict or identify all such factors. Consequently, you should not consider the preceding to be a complete discussion of all potential risks or uncertainties.
References
[1] U.S. Centers for Disease Control and Prevention (CDC). Arthritis Related Statistics. Available here. Accessed on October 17, 2007.
[2] National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, U.S. Department of Health and Human Services. Handout on Health: Osteoarthritis. Available here. Accessed on October 17, 2007.
[3] Arthritis Foundation. Available at: http://www.arthritis.org. Accessed on October 17, 2007.
[4] U.S. Centers for Disease Control and Prevention (CDC). [CDC (2007) Update: National and State Medical Expenditures and Lost Earnings Attributable to Arthritis and Other Rheumatic Conditions-United States, 2003. MMWR Morb Mortal Wkly Rep, 56(01):4-7].
Endo Pharmaceuticals Inc.
Precursors To Bone-Eating Cells Likely Target Of Next-Generation Arthritis Treatments
March 4, 2008
Researchers have learned more about how a leading drug prevents certain types of arthritis from eating away at bone, according to a study published in the March edition of the Annals of the Rheumatic Diseases. The findings may soon enable physicians to tell patients quickly whether or not they will respond to current therapies. In addition, the findings may help with the design of new drugs that prevent arthritis-related bone loss, but with fewer side effects. The work was also presented at the annual meeting of the Orthopaedic Research Society in San Francisco.
Psoriatric arthritis (PsA), like rheumatoid arthritis, is an autoimmune disease, where the body mistakes its own tissues for an infection and attacks them. The attack comes in the form of inflammation, the unleashing of attack cells, chemicals and fluids meant to remove bacteria or viruses, but that also destroy human cells and tissues in too high amounts. Psoriatic arthritis affects about six percent of those suffering from the autoimmune skin condition psoriasis, and can severely damage joints and bones. One study found that, within two years of first diagnosis, almost half of PsA patients experience holes in their bones, visible on X-ray scans, that define erosive arthritis.
While traditional PsA treatments include NSAIDs or steroids to stop inflammation, the recent focus has been on newer drugs that interfere with tumor necrosis factor (TNF), an inflammatory chemical central to both normal immune function and autoimmune disease. Such drugs go beyond reducing inflammation to prevent bone damage, but how they do so has remained unclear. A better understanding is important because, although newer drugs suppress immune attack on joints, they also leave patients vulnerable to infection. The hope is that the next generation of treatments will not.
In the current study, researchers examined the molecular effects of etanercept (Enbrel), a genetically engineered drug produced by Amgen and approved by the U.S. Food and Drug Administration in 1998. Going into the study, researchers knew that Enbrel attaches to TNF and removes it from joints and the bloodstream, reducing inflammation, tenderness and pain. The current study suggests that anti-TNF therapy may work in another way as well.
Human bone must continually recycle itself to maintain its strength. Under the control of signaling molecules, two paired cell types make recycling possible in a careful balance. Osteoclasts “eat” or excavate aging bone to make way for new bone, while osteoblasts build new bone.
“In erosive psoriatic arthritis, mistaken immune signals tell osteoclasts to keep digging, as if they were trying to get at an infection buried inside the bone,” said Edward M. Schwarz, Ph.D., professor of Orthopaedics within the Center for Musculoskeletal Research at the University of Rochester Medical Center, and an author of the study. “Our study confirms that we have two ways of measuring this process, and provides the first clues about how to prevent it.”
As it does with many cell types, the body keeps pools of osteoclast precursors on hand, inactive until needed. In past studies, Schwarz and his team found an increased frequency of osteoclast precursor in the peripheral blood of patients with PsA. Past work has also shown that TNF plays a role in the formation of osteoclast precursors, and that TNF blockers decrease osteoclast precursor frequency.
In 2003, Schwarz and team guessed that osteoclast precursors must come from the bone marrow near affected joints. In the human embryo, one layer of stem cells develops into the common source of cells making up bone marrow, blood and immune cells. One particular stem cell line goes on to form macrophages, immune cells that dissolve any bacteria they encounter. A related stem line becomes osteoclasts, which dissolve any bone they encounter. Something in the bone marrow of PsA patients, an inflammatory signaling molecule perhaps, is directing cells, which would otherwise become macrophages, to turn instead into pockets osteoclast precursors, researchers said.
The current study confirmed their guess by capturing images of another factor closely tied with erosive arthritis: bone marrow edema. Decades ago, using relatively crude imaging technologies, researchers first recognized what looked like water deposits in the otherwise fatty bone marrow near affected joints. The pockets, mistaken for fluid, at that time were labeled edema, another word for swelling. The current study, with access to modern imaging technologies, has proven is that the watery bone marrow pockets seen in PsA patients are filled with, not water, but instead osteoclast precursors, which like most cells, are made mostly of water.
Researchers are excited by the possibility that watery pockets of macrophage-related osteoclast precursors might be taken out of commission by a precise treatment before they start damaging bone. The current work takes advantage of new image analysis technology, developed by Rochester, N.Y.-based VirtualScopics Inc., to show for the first time that the high level of osteoclast precursors seen in erosive arthritis originates in bone marrow lesions near affected joints. The team has started the search for a molecule or mechanism in bone marrow, which they believe must exist, that converts its normal fatty content into osteoclast precursor cell lesions at the behest of inflammatory signaling.
Study Details
Twenty patients with erosive psoriatic arthritis were enrolled to receive etanercept twice weekly for 24 weeks. Biomarkers were measured and clinical assessments performed at baseline, 2, 12 and 24 weeks. Gadolinium-enhanced magnetic resonance images were obtained at baseline and 24 weeks to measure bone marrow edema. All patients were given subcutaneous injections of etanercept, 25 mg twice weekly for 6 months. This study was approved by the Institutional Review Board at the University of Rochester Medical Center, and informed consent was obtained from all patients.
The study found that patients saw improvement in the 68 joints analyzed, including less swelling and pain, according to standard measures of joint function. Secondly, patients treated with anti-TNF therapy saw a dramatic drop in the median level of osteoclastic precursor cells (OCP) in patients’ blood, from 24.5 OCP per million white blood cells to 7 (p = 0.006) after 6 months of treatment. The rapid decline in OCPs after anti-TNF therapy provides one explanation for the anti-erosive effects of TNF blockade in PsA.
A second, related explanation may be seen in the bone marrow edema results, albeit with limitations. Past studies have suggested that bone marrow edema predicts regions where severe bone erosions are soon to develop. To address this hypothesis, Schwarz and colleagues designed a study to assess the impact of anti-TNF therapy on the edema using gadolinium enhanced MR images. The longitudinal images provided researchers with an “unparalleled view” of the psoriatic joint, and the ability to accurately measure the borders of edema lesions in the bone marrow surrounding each joint.
The study found that edema volume decreased in 47 joints, indicating that the inflamed bone marrow was returning to its normal fatty content following therapy. However, the analysis also revealed an increase in edema-like lesions in 31 joints at 6 months. The team believes that those signals were caused by as yet unidentified changes in the bone marrow not related to bone marrow edema and osteoclast precursors, but further studies will be needed to confirm that.
“A simple blood test can determine a person’s osteoclast precursor levels,” Schwarz said. “That should soon change medical practice as we can tell by OCP levels if a person has erosive disease. If those levels fail to drop immediately with anti-TNF therapy, that person is likely among the 30 percent of people who don’t respond to etanercept. We can spare them the side effects and perhaps switch them to drugs like rituximab or abatacept, which are approved for rheumatoid arthritis patients that do not respond to anti-TNF therapy. While the blood test can tell you if you have PsA, it cannot tell which joints are affected. That feat has been achieved in this study for the first time with new MRI technology, which shows which joints have pre-erosive, osteoclast precursor lesions forming in the nearby bone marrow. These two tests, done in serial fashion, should allow for earlier diagnosis and more precise treatment of psoriatic erosive arthritis.”
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Source: Greg Williams
University of Rochester Medical Center
Effect Of Tumor Necrosis Factor A Inhibitors On Heart Failure Risk In RA Patients
February 29, 2008
A chronic autoimmune disease, rheumatoid arthritis (RA) is characterized by persistent inflammation of the synovial membrane and progressive joint destruction. Beyond loss of mobility, sufferers face a high risk of heart failure. An inflammatory cytokine known for contributing to the development of RA, tumor necrosis factor a (TNFa) has also been implicated in cardiovascular disorders. Inhibition of TNFa has opened promising new treatment options for RA patients. Anti-TNF drugs such as infliximab, etanercept, and adalimumab have been shown to not only diminish signs and symptoms of the disease, but also prevent joint damage. However, in cardiac trials, TNFa inhibitors have shown no more positive effects on heart failure risk — and sometimes less — than placebo.
Does TNFa inhibition prevent heart failure in RA patients — or promote it? That’s the critical question Dr. Joachim Listing and a team of specialists with the German Rheumatism Research Centre in Berlin set out to answer. Featured in the March 2008 issue of Arthritis & Rheumatism , their study indicates that anti-TNF therapy does a patient’s heart more good than harm, when it successfully reduces the inflammatory toll of RA.
To clearly assess the role of TNFa inhibitors in heart failure risk, the researchers analyzed a 3-year span of disease activity and cardiovascular incidents in 4,248 RA patients enrolled in an ongoing Germany-wide study of biologic therapy. At the time of enrollment, 2,757 of the subjects had started treatment with an anti-TNF drug — infliximab, etanercept, or adalimumab — and 1,491 had started a new disease-modifying antirheumatic drug (DMARD). Within the study period, several hundred of the patients were also treated with glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or COX-2 inhibitors. Over 78 percent of the patients were women. The mean age at baseline was 53.7 years for the anti-TNF group and 56 years for the DMARD controls.
Recorded at baseline and regular intervals through the 60-month follow-up, data on every patient included C-reactive protein level, duration of morning stiffness, and the number of tender and swollen joints, based on the 28-joint count Disease Activity Score (DAS). Cardiovascular events, whether acute or congestive, were also noted. Researchers used Cox proportional hazards models to investigate the impact of disease-related and treatment-specific risk factors on the development or worsening of heart failure.
At baseline, RA patients in the anti-TNF group had significantly more active disease, more physical limitations, and more heart problems than patients in the control group. Not surprisingly, the incidence rates of heart failure were significantly higher — more than double — for patients with a cardiovascular condition at the start of treatment than for those in good heart health. After adjusting for age, sex, body mass index, and prevalence of cardiovascular events, an increased risk of heart failure was found in patients with low functional capacity and high disease activity. Notably, a 2-point increase in the DAS28 score resulted in a 1.8-fold increase in heart failure risk.
When adjusting for functional capacity and disease activity at follow-up, along with the standard risk factors, the contribution of anti-TNF therapy to heart failure risk was insignificant. The small residual risk was balanced by the treatment’s effectiveness in reducing inflammation, ultimately protecting the heart and other vital organs in addition to the joints. In contrast, COX-2 inhibitors and glucocorticoids, which tend to promote elevated blood pressure and insulin resistance, were associated with an increased risk of heart disease and heart attack.
Confirming the grave risk of heart failure for patients with severe rheumatoid arthritis, especially those with highly active disease, this study also sheds light on the benefits of treatment with TNFa inhibitors to the heart and whole body. “Our data suggests that controlling the inflammatory activity of RA not only leads to better outcome of the rheumatic disorder, but also contributes to a reduction of cardiovascular risk,” Dr. Listing notes. He calls attention to the need for more research to weigh the positive effects of glucocorticoids, such as cellular proliferation, against their harmful effects to the cardiovascular system. Finally, he urges caution in prescribing any drug that may be hazardous to the heart of a vulnerable patient. “Screening for cardiac risk factors and effective treatment of both the rheumatic disorder and the cardiac disease are essential,” Dr. Listing stresses.
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Article: “Does Tumor Necrosis Factor a Inhibition Promote or Prevent Heart Failure in Patients With Rheumatoid Arthritis? Joachim Listing, Anja Strangfeld, J?rn Kekow, Matthias Schneider, Andreas Kapelle, Siegfried Wassenberg, and Angela Zink, Arthritis & Rheumatism , March 2008.
Source: Amy Molnar
Wiley-Blackwell
NICE Launches New Era For Millions With Osteoarthritis, UK
February 28, 2008
In guidelines hailed by Arthritis Care as a giant leap towards more patient-centred services, the National Institute of Health and Clinical Excellence (NICE) today recommends that osteoarthritis (OA) patients needing NHS joint surgery are referred promptly when other treatments have failed them.
For the first time, NICE stipulates that age, obesity, gender, smoking, or people’s other illnesses should not dissuade GPs from referring them for joint replacement surgery where this is clinically appropriate.
Breaking with a past in which people were often kept waiting until their joints had worn out, the new NICE guidelines for England and Wales recommend action before people experience severe pain or prolonged loss of function. This may include consideration for surgery once osteoarthritis starts having a ’substantial impact’ on quality of life.
‘It’s fantastic news for people with OA. Surgery may be the kindest cut when other treatments have failed, especially as modern techniques mean you needn’t wait to lose a joint to save it. The clarity of these guidelines should bring some much-needed consistency’, said Neil Betteridge, chief executive of Arthritis Care, the UK’s leading organisation for people with any form of arthritis.
Some 8.5 million people in the UK have osteoarthritis. Symptoms include pain and stiffness in the joints, often resulting in sleeplessness, fatigue, and depression. Mobility and ability to work may be compromised. With a plummeting income, involvement in sport and social life can diminish, leading to isolation, depression, and a loss of self-esteem.
‘Osteoarthritis can hit you like a truck. Many people develop it quite early. One day you have a life brimming with opportunity, and bustling with activity, the next, you are painfully aware that your skeleton is on strike. You’re wondering how to take your shoes off, do the shopping, lift the kids, get into work. This guidance will help people with OA and doctors work together to take charge of the condition - with the right medical support, having osteoarthritis doesn’t mean you have to lose your get-up-and-go, just find new ways of maximising it,’ said Jo Cumming, Arthritis Care’s helplines manager, who was diagnosed with osteoarthritis in her early 40s and was a patient representative on the NICE osteoarthritis Guideline Development Group.
As well as emphasising the need for surgery referral where joint pain has a ’substantial impact’ on quality of life, NICE has set out a groundbreaking package for the holistic assessment and active management of osteoarthritis.
‘It’s robust, far-sighted, and innovative, a genuine first. Until now, people with OA have had a Cinderella service, and have often felt sidelined by the system. OA has never even featured in the government’s pay-for-performance targets for GPs, making those who live with it feel short-changed. Now millions with OA can demand the treatment to which they are entitled, and which NICE says will boost their ability to live life fully’, said Betteridge.
The new standard recommends a whole-person prescription which may include: exercise, weight management, pain relieving gels and medications, as appropriate, and provision by health professionals of myth-busting information to help people understand their osteoarthritis and the control of its symptoms.
‘It recommends the holistic and can-do approach that Arthritis Care has always promoted. The package means that people should never again be told that “nothing can be done”, that “osteoarthritis is a natural part of getting old”, and something you “just have to put up with,” said Betteridge, whose organisation pioneered arthritis self-management courses in the UK, and provides information, free helplines, and training.
‘These guidelines are a giant leap in the right direction. But they mean little if not supported by the range of services needed in GP’s surgeries, hospitals and the wider community. The real challenge is to ensure that NHS commissioners provide doctors, nurses, and all allied health professionals with resources to put these patient-centred recommendations into action’, he said.
‘If properly implemented, the NICE guidelines can become a framework for the ’smart’ healthcare of the future - partnerships in which health professionals and patients team up to provide active management and effective coping strategies for people with long term conditions like osteoarthritis. With an ageing population, the way forward must be a future not of “patients” but of “people living successfully with arthritis within the family, community and workplace”‘, added Betteridge.
Arthritis is the UK’s biggest single cause of physical disability, affecting around nine million Britons of all ages. Established in 1947, Arthritis Care is the UK’s largest voluntary organisation committed to supporting people with all forms of arthritis. It predates the NHS by one year and pioneered self-management training in the UK, offering free courses all round the country. It works to represent people with arthritis and to lobby decision-makers on their behalf. It has around 350 branches UK-wide, a free information helpline, produces a range of information booklets plus the award-winning Arthritis News, and it actively campaigns locally, nationally and internationally for people with arthritis.
Arthritis Care
Doctors Should Watch For Depression In Arthritis Patients
February 21, 2008
Patients with rheumatoid arthritis are twice as likely to experience depression but are unlikely to talk to a doctor about it, according to researchers at the University of North Carolina at Chapel Hill.
Rheumatoid arthritis (RA) the most common form of chronic inflammatory arthritis is a debilitating disease characterized by inflammation of joint tissues, persistent pain, functional disability, stiffness and fatigue.
Betsy Sleath, PhD, a professor at the UNC School of Pharmacy, said that although depression in primary care settings has been well examined, no previous studies have looked at whether rheumatologists and RA patients discuss depression during medical visits.
In a new study lead by Sleath and published in this month’s issue of Arthritis Care & Research, researchers found that almost 11 percent of RA patients had moderately severe to severe symptoms of depression. Those who were rated as being more restricted in their normal activities were significantly more likely to have these symptoms.
The study also found that only one in five of the patients who showed symptoms of depression discussed it with their rheumatologists. Those who did were always the ones to bring up the topic, not the physician. When depression was brought up, it was often not discussed at any length.
Sleath said when patients visit their specialist, their arthritis is understandably their main focus but rheumatologists should consider addressing both RA and depression when they see their patients.
“Chronic diseases can greatly affect a patient’s psychosocial well-being, and depression can also affect a patient’s adherence to treatment regimens,” Sleath said. “Since many arthritis patients see their rheumatologist more often then their primary-care physician, we recommend that rheumatologists take steps to screen patients for signs of depression.”
Sleath said if physicians are uncomfortable discussing depression with their patients, they should consider having their office staff administer a brief depression screening before the patients’ visits in order to identify problems early on.
In addition to screening for depression, Sleath said it is important for patients to have access to appropriate treatment. Rheumatologists can treat the depression themselves, refer patients to a mental health professional or communicate with the patient’s primary-care physician to coordinate a treatment plan. Also, given how common depression is in these patients, rheumatology training programs should educate physicians about the importance of screening for and treating depression, she said.
The study included 200 arthritis patients from four rheumatology clinics with eight participating doctors. Patient visits were audiotaped, and patients were interviewed after their medical visits using a questionnaire to assess depressive symptoms.
The study is titled “Communication about Depression during Rheumatoid Arthritis Patient Visits.” The other authors of the study are Betty Chewning, PhD, of the University of Wisconsin; Gail Tudor, PhD, from Husson College in Bangor, Maine; Brenda M. De Vellis, PhD, and Robert F. De Vellis, PhD, professors of health behavior and health education in the UNC School of Public Health; Morris Weinberger, PhD, the Vergil N. Slee Distinguished Professor of Healthcare Quality Management and the director of the doctoral program in the UNC School of Public Health’s health policy and administration department; and Ashley Beard, a PhD candidate at the UNC School of Pharmacy.
University of North Carolina at Chapel Hill
210 Pittsboro St. Campus Box 6210
Chapel Hill, NC 27514
United States
http://www.unc.edu
Arthritis Sufferers Fund Arthritis Research
February 18, 2008
The Queensland and Northern New South Wales Lions Medical Research Foundation, long time supporters of the Brisbane research community, have confirmed funding of $1.2 million for scientists at UQ’s Diamantina Institute.
Dr Gethin Thomas will be the inaugural recipient of the $300,000 three-year fellowship, which will fund his research investigating the causes of ankylosing spondylitis (AS).
This is a form of arthritis affecting the spine resulting in joint fusion and immobility, and osteoporosis, a disease characterised by bone loss and frequent fracture.
“This funding will enable us to focus on our longer-term goals of identifying the underlying causes of these diseases and developing new drugs and therapies,” Dr Thomas said.
“There is an urgent need for new therapies in these diseases that will enable reversal of disease damage.
“The current therapies can only prevent progression of AS and osteoporosis but cannot repair already damaged bones and joints.
“Unfortunately sufferers are frequently not diagnosed until fracture or loss of mobility by which time degeneration of the bones or joints is already significant.”
Irene Dunning, Lions Foundation Chairman, said she was pleased Dr Thomas had received the first installment of the new Fellowship.
“I think it’s good to be supporting something which will potentially help a lot of Lions members,” she said.
“Osteoporosis and arthritis are diseases that affect many Lions members and their families and friends.
“Lions members will further contribute to the research by volunteering as participants in the studies providing a valuable resource for our research efforts and creating a mutually beneficial synergy.
The University of Queensland, Brisbane Australia
FDA Agrees To Review Cimzia(R) File For The Treatment Of Rheumatoid Arthritis
February 17, 2008
UCB announced that the U.S. Food and Drug Administration (FDA) agreed to accept, for filing and review, a biologics license application (BLA) for Cimzia(R) (certolizumab pegol) for the treatment of adult patients with active rheumatoid arthritis (RA). Cimzia(R) is an investigational agent. If approved, Cimzia(R) will be the first and only PEGylated anti-TNF (Tumor Necrosis Factor) biologic therapy available for the treatment of rheumatoid arthritis.
“As a new anti-TNF, we believe that Cimzia(R) would provide an important new option for people living with this disease,” said Olav Hellebo, President Inflammation Operations, UCB.
The BLA is based on data from more than 2,367 patients and includes three multi-center, placebo-controlled Phase III trials which were recently presented at the American College of Rheumatology (ACR) Annual Scientific Meeting.
In these studies, Cimzia(R), given with methotrexate, was shown to be significantly more effective than methotrexate alone for the inhibition of joint damage progression in patients with active RA as early as 24 weeks (RAPID 1 and RAPID 2). Cimzia(R) was shown to rapidly reduce the signs and symptoms of active RA with peak ACR50 and 70 responses achieved at 14 and 16 weeks. Improvement in physical function and quality of life measures were also seen for up to one year (RAPID 1). Further, Cimzia(R) administered as monotherapy showed significant improvement in signs and symptoms of RA from week 1, and this benefit was maintained through week 24 (Study 011). The most commonly occurring adverse reactions were headache, nasopharyngitis, and upper respiratory tract infections. Reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma), consistent with findings from other trials in the anti-TNF class.
Preparation for submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) for Cimzia(R) in the treatment of RA is ongoing, with filing planned in the first half of 2008.
In September 2007, Cimzia(R) was approved in Switzerland for the treatment of Crohn’s disease and it was launched in January 2008.
About Rheumatoid Arthritis
RA is a progressive autoimmune disease that causes chronic inflammation of the joints. It is estimated that five million people suffer from RA globally, with 0.3 percent to 1 percent of the population in industrialized countries suffering from the disease. Women are three times more likely to be affected than men. Although it can affect people of all ages, the onset of RA usually occurs between the ages of 35-55.
Traditional treatments for RA include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs), with biological therapies a more recent addition.
About UCB
UCB, Brussels, Belgium (http://www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology. UCB focuses on securing a leading position in severe disease categories. Employing around 12,000 people in over 40 countries, UCB achieved revenue of 3.5 billion euro in 2007 on a pro forma basis. UCB S.A. is listed on Euronext Brussels.
UCB Forward-Looking Statement
This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to the development and commercialization of certolizumab pegol. Among the factors that could cause actual results to differ materially from those indicated by such forward- looking statements are: the results of research, development and clinical trials; the timing and success of submission, acceptance, and approval of regulatory filings; the time and resources UCB devotes to the development and commercialization of certolizumab pegol and the scope of UCB’s patents and the patents of others.
UCB
http://www.ucb-group.com
Rheumatic Complaints Not Just A Problem For The Western World
February 17, 2008
We like to complain about our aches and pains, but rheumatism is not only the preserve of western society. A comprehensive survey of rheumatic diseases in China, published in the open access journal Arthritis Research & Therapy, reveals that rheumatic complaints are also common in China. The survey suggests that the incidence of certain rheumatic diseases in the Chinese population is now becoming more like that of Western countries.
This latest survey is the first of its kind, using data compiled from 38 previously published studies covering over 240,000 adults from 25 provinces and cities. It shows that the prevalence of osteoarthritis (OA) in China is similar to other Asian Pacific and western countries. However, rheumatic diseases in the Chinese appear to affect different sites than that of Caucasian populations. The sites of complaint tended to be the lumbar spine, knee joint and cervical spine, whereas Caucasian populations tend to suffer OA more in the hips and hands. The prevalence of ankylosing spondylitis in China was also similar to Caucasians and similarly linked to certain genetic markers.
The study also shows that elderly people in the north of China suffer the most from these painful and chronic joint complaints including osteoarthritis and rheumatoid arthritis. The prevalence of rheumatoid arthritis (RA) in mainland China ranged from 0.2% to 0.37%, a prevalence similar to most Asian and South American countries, but lower than that in Caucasians. “Interestingly, we found that the prevalence of rheumatoid arthritis in urban and suburban parts of Taiwan was closer to the Caucasians rate,” says Dr Qing Yu Zeng who led the study. “These areas are more developed than mainland China. Apart from genetic factors, it looks as if environmental and socio-economic factors might be important risk factors for RA. That’s something we’d certainly like to investigate further.”
The survey also looked into a number of rarer rheumatic conditions and found evidence that certain ethnic groups might be more susceptible than others.
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1. Rheumatic diseases in China Qing Yu Zeng, Ren Chen, John Darmarwan, Zheng Yu Xiao, Su Biao Chen, Richard Wigley, Shun Le Chen and Nai Zheng Zhang Arthritis Research & Therapy (in press)
Article available at journal website: http://arthritis-research.com/.
All articles are available free of charge, according to BioMed Central’s open access policy.
2. Arthritis Research & Therapy is an international, peer-reviewed online and print journal, publishing original research, reviews, commentaries and reports. Studies relate to the rationale and treatment of arthritis, autoimmune disease and diseases of bone and cartilage. The journal is edited by Prof Peter E Lipsky (USA) and Prof Sir Ravinder N Maini (UK) and has an Impact Factor of 3.8.
3. BioMed Central (http://www.biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
Bone Medical Developing Potentially First Rheumatoid Arthritis Drug To Treat Both IL6 And TNF, Australia
February 17, 2008
New data from the Bone Medical Ltd (ASX: BNE) rheumatoid arthritis (RA) programme shows that its lead drug candidate BN006 is capable not only of down-regulating TNF secretion, but also of inhibiting secretion of IL6.
BN006 has been developed as an inhibitor of secretion of TNF, one of the cytokines involved in the inflammatory process that perpetuates RA. It has now been found that BN006 also inhibits IL6 secretion by macrophage type cells in culture with a clear dose-response relationship. This is significant as IL6 is becoming recognised as an important target alongside TNF in for new therapeutics in treatment of RA.
Although no such products have yet arrived on the market, one therapy targeting IL6 (Roche’s Actemra) is in Phase III clinical trials. Roche recently reported the generation of positive data from its latest studies.
Professor Peter Brooks, Executive Dean of the Faculty of Health Sciences at the University of Queensland and a renowned world expert in arthritis, said “IL6 is one of the agents which is instrumental in creating the vicious cycle of inflammatory events in RA and could be as important in treatment of RA in the future as TNF is at present.”
Both Actemra and the current anti-TNF treatments such as Remicade, Infliximab and Eternacept, are all monoclonal antibodies which need to be injected. Bone’s candidate is a small molecule which could be orally available making the treatment much more patient friendly.
Dr Roger New, Chief Scientific Officer of Bone Medical, pointed out “the current monoclonal antibody treatments all target just one single component in the inflammatory process - either TNF or IL6. To have one molecule which affects both of these cytokines together could make it a much more powerful approach to treatment.”
About Bone Medical Limited
Bone Medical Limited is an international biopharmaceutical development company positioned to exploit the growing market in the treatment of bone disease particularly in osteoporosis and arthritis. Bone has a portfolio of biopharmaceutical development projects for the treatment of bone disease including,
– Osteoporosis
- Capsitonin™ oral calcitonin
- CaPTHymone™ oral parathyroid hormone
- bone cell regulators BN005 & BN008
– Arthritis
- TNF regulators BN006
- joint protection & collagen tolerance BN007
Bone Medical Ltd
Arthritis Foundation Launches Year-Long Recognition Of 60th Anniversary
February 17, 2008
The Arthritis Foundation began a year-long observance of 60 years as the nation’s leading organization dedicated to ending the pain, disability devastation of arthritis. While great strides have been made in the treatment and understanding of arthritis, the disease remains the most common form of disability in the U.S.
“The progress we have made in improving the treatment of arthritis over the past 60 years is truly amazing,” said John H. Klippel, M.D., CEO of the Atlanta-based health organization. “In 1948, we were just beginning to learn about the role of the immune system in causing joint inflammation and damage in diseases like rheumatoid arthritis and juvenile arthritis and knew virtually nothing about the genetic links to diseases like osteoarthritis. The idea of replacing entire joints, now a routine procedure with more than 600,000 total knee and hip replacements done each year, was once more science fiction than science.”
While Dr. Klippel recognizes the progress and is proud of the role played by the Arthritis Foundation, he sees a looming public health crisis in the near future if greater steps are not taken.
“Arthritis now affects 46 million Americans, that’s one in five people, and costs the U.S. economy $128 billion each year,” added Dr. Klippel. “By 2030, it is projected that 67 million Americans will have arthritis and the costs associated with providing care for this many people will have a profound impact on the health care system.”
The Arthritis Foundation sees increased federal funding for arthritis research and public health programs and greater access to early detection and more comprehensive arthritis healthcare as a key means of addressing this pressing issue. The Foundation is currently mobilizing its grassroots network of thousands of volunteers to encourage Congress to pass the Arthritis Prevention, Control, and Cure Act (APCCA).
In recognition of the advancements made over the past 60 years, the Foundation has compiled a list of milestones in the fields of arthritis awareness, advocacy, research and treatment since 1948. Below are a few highlights.
- 1950 - Nobel Prize awarded to Edward Kendall, MD, Philip Hench, MD and Thadeus Reichstein, MD, for investigations of the hormone cortisone in the treatment of rheumatoid arthritis (RA).
- 1968 - Dr. David MacIntosh pioneers knee replacement surgery.
- 1974 - Congress passes the National Arthritis Act, which legislates funding for development of comprehensive arthritis care centers, assistance for medical schools and establishment of a national commission to develop long-range plans related to arthritis.
- 1980 - Researchers funded by the Arthritis Foundation discover evidence thatLyme disease is transmitted by ticks.
- 1986 - National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS) is established.
- 1998 - FDA approved the first biologic (TNF inhibitor) for the treatment of RA.The entire list of “60 Milestones in Arthritis” is available at http://www.arthritis.org.
About the Arthritis Foundation
The Arthritis Foundation is the leading health organization addressing the needs of some 46 million Americans living with arthritis, the nation’s most common cause of disability. Founded in 1948, with headquarters in Atlanta, the Arthritis Foundation has multiple service points located throughout the country.
The Arthritis Foundation is the largest private, not-for-profit contributor to arthritis research in the world, funding more than $380 million in research grants since 1948. Celebrating its 60th anniversary this year, the foundation helps individuals take control of arthritis by providing public health education; pursuing public policy and legislation; and conducting evidence-based programs to improve the quality of life for those living with arthritis. Information is available 24 hours a day, seven days a week at http://www.arthritis.org.
