Sleep Apnea Linked To Insulin Resistance, Independent Of Obesity
In a study that addressed the issue of insulin sensitivity with respect to sleep disordered breathing (SDB), Naresh Punjabi, M.D., Ph.D. sought to examine the relationship between SDB and insulin resistance using the best tools at his disposal to do so.
The results definitively link SDB to pre-diabetic changes in insulin production and glucose metabolism. It was published in the first issue for February of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
“In the past researchers have used body mass index, or BMI, as a proxy measure for body fat, but we know this to be a variable and crude tool to assess the true percentage of body fat,” said Dr. Punjabi. “In addition, previous studies have used surrogate measurements to assess the body’s response to insulin without investigating the interaction that occurs between reduced insulin sensitivity and increased insulin production in the body.”
To address the shortcomings of previous studies, Dr. Punjabi and colleagues used two tools in their investigation into the link between SDB and insulin resistance: dual-energy x-ray absorptiometry (DEXA), a highly precise technique for assessing body fat, and frequently sampled intravenous glucose tolerance test (FSIVGTT), which provides a detailed picture of the subject’s insulin sensitivity over time, rather than a simple snapshot at a specific moment.
They recruited 118 subjects, 39 who had no SDB, and 79 who were newly diagnosed with SDB but who had not been treated. Each subject underwent a sleep study to assess their level of SDB, and then underwent a FSIVGGT to determine their glucose metabolism and insulin sensitivity/production the following day.
“Our major finding was that, as we suspected, SDB was strongly associated with a decrease in the three major metabolic pathways that the body uses to metabolize glucose – insulin sensitivity, glucose effectiveness, and pancreatic cell function – independent of adiposity,” said Dr. Punjabi. “What our research tells us is that SDB is characterized by multiple physiological deficits that increase the predisposition for type 2 diabetes mellitus.”
Sleep Apnea linked to the Progression of Liver Disease
In another study published in the same issue of the Journal, other researchers from Johns Hopkins Bayview Medical Center Bariatric Surgery Clinic found that the chronic intermittent hypoxia that often characterizes OSA, a common form of SDB, is also independently linked to the progression of liver disease.
In this study, researchers recruited 90 severely obese patients presenting for bariatric surgery at without known diagnoses of obstructive sleep apnea. Each patient underwent a sleep study and blood tests for markers of liver function, insulin resistance, and systemic inflammation. And, because standard practice for patients undergoing bariatric surgery is to biopsy the liver, the researchers were able to analyze liver tissue for signs of disease and link it to the severity and type of sleep disordered breathing they observed during the sleep study.
The results validated the link between OSA and insulin resistance, and further linked it to the level of hypoxemia experienced during the night versus simply the number of apneic events. Strikingly, of the patients whose liver tissue was analyzed, those who were observed to have severe nocturnal hypoxemia also exhibited “ballooning” of their hepatocytes and a pericellular fibrosis of the liver, indicating liver injury.
“We demonstrated that the severity of nocturnal oxyhemoglobin desaturation predicted the severity of insulin resistance and might be implicated in the development of liver disease. In contrast, severe obesity was associated with high levels of serum c-reactive protein (CRP), indicating systemic inflammation,” said lead researcher, Vsevolod Y. Polotsky, M.D., Ph.D., of Johns Hopkins’ Asthma and Allergy Center. “Interestingly, there was no relationship between the severity of nocturnal hypoxemia and serum CRP. This suggests that that obesity and OSA have distinct metabolic, inflammatory and hepatic profiles, which act in different detrimental ways on the liver.”
“We hypothesize that severe obesity per se acts as a ‘first hit’ in the progression of liver disease, inducing hepatic steatosis, whereas the presence of the chronic intermittent hypoxemia that often characterizes OSA acts as a ’second hit’. The hypoxic stress of OSA may induce oxidative stress in the livers of patients with severe obesity, leading to further inflammation.”
The clinical implications of the findings are clear: obesity and obstructive sleep apnea exert separate and perhaps additive negative effects on insulin resistance and the liver, and each disorder must be treated concomitantly in order to address the secondary complications.
“Our data suggest that patients with OSA and severe nocturnal hypoxemia should be screened for liver disease and, conversely, patients with liver disease should be screened for OSA,” said Dr. Polotsky.
“We have developed a mouse model of intermittent hypoxia and have demonstrated that a combination of a high-fat diet and intermittent hypoxia leads to liver disease in those mice. We plan on continuing to use the model in future research. We plan to examine whether treatment of OSA with continuous positive airway pressure can improve or reverse liver disease.”
Severity of OSA Linked to Sedentary Lifestyle
Not only is OSA linked to insulin resistance and liver disease independent of obesity, but at least one risk factor is also common to obesity and OSA: prolonged daytime sitting or standing. Even when the sedentary lifestyle does not lead to obesity, it may still lead to OSA and its concomitant health risks, according to another research article in the first issue for February of the American Journal of Respiratory and Critical Care Medicine.
“Overnight fluid displacement from legs, related to prolonged sitting, may play a previously unrecognized role in the pathogenesis of OSA,” wrote principle investigator, T. Douglass Bradley, M.D., professor of medicine and director of the Centre for Sleep Medicine and Circadian Biology at the University of Toronto,
The research also found that the volume of fluid shift was directly linked to the hours in a day that the subject reported sitting or standing and was independent of the excess weight that often accompanies sedentary lifestyles.
“In more recent years, the introduction of modern technologies into the workplace has greatly reduced the need for physical activity and increased the number of jobs requiring prolonged sitting, during which absence of the contraction of calf muscles leads to dependent fluid accumulation in the legs that is proportional to the time spent in that position,” explained Dr. Bradley. “When assuming the recumbent position at bedtime, the fluid retained in the legs during the day in redistributed to the upper body. It is therefore plausible that some of the displaced fluid might reach the neck and predispose to upper airway constriction.”
To determine whether that, in fact, was the case, the researchers recruited 23 nonobese subjects who were being evaluated for suspected OSA and performed standard sleep studies that assessed each subject for sleep stages and number of arousals, as well as oxygen saturation of the blood. The circumferences of their calves and necks were also measured at bedtime and upon awakening, before they got up.
Indeed, they found that the only significant correlate factor with respect to severity of OSA was the overnight change of fluid volume in the leg, which explained 67% of the variance in OSA severity. The change in fluid in the leg was, in turn, directly related to the amount of time the subject reported sitting each day.
“An important implication of our observations is that sedentary living may predispose to OSA not only by promoting obesity, but also by causing dependent fluid accumulation in the legs, which can shift rostrally to the neck overnight,” said Dr. Bradley.
This finding may also help explain why 40 percent of patients with OSA are not obese, and why a reduction in OSA has been described when subjects begin exercise programs, even in the absence of weight loss.
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Article adapted by Medical News Today from original press release.
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Source: Keely Savoie
American Thoracic Society
Tougher Health And Safety Law Demands Tougher Drugs Policies
New legislation that has come into effect this month will introduce tougher penalties on businesses that breach health and safety regulations. According to Concateno, Europe’s leading drug testing company, the new legislation adds a further incentive to businesses considering the introduction of an effective anti-drugs policies and drug testing in the workplace.
The Health and Safety Offences Act 2008, which was announced in last October and came into effect on January 16th 2009, provides courts with increased sentencing powers that could include prison sentences for individuals found responsible for health and safety breaches and increase the maximum fines for offences.
Neil James, head of sales for Concateno’s workplace division said: “Alongside the tougher legislation for corporate manslaughter that has been introduced in recent years, the new Act makes it vital for companies to manage down risks in their businesses, and also to demonstrate that they have undertaken due diligence to indentify and prevent causes of accidents.”
He added: “Employee drug misuse can be a contributory cause of accidents at work and a company’s management could potentially be held responsible if they haven’t taken sufficient action. Businesses have the ability and responsibility to proactively address this situation.”
To be effective, a company’s drug and alcohol policy needs to include deterrents against the inappropriate use of drugs and alcohol – through education; Employee Assistance Programmes that help employee address their drugs problems through appropriate support and treatment; and through testing, whether pre-employment, at random, or following incidents.
An introduction to Concateno
Concateno brings together the leading drug and alcohol testing organisations in Europe to form a global first in the field: a service provider with the facilities and expertise to genuinely deliver test programmes to meet any requirement – from point-of-care instant tests, through to state-of-the-art laboratory analysis for any biological specimen including urine, oral fluids, hair and sweat.
Concateno’s 300 staff support more than 8,000 customers globally, and the group performs approximately eight million tests annually. An integrated network of more than 500 sample collection officers, trained in-house in chain-of-custody procedures, supports clients around the world.
Committed to the highest levels of accreditation and quality assurance, Concateno works actively within the industry to improve existing best practice. This includes ISO 17025 (independently audited by UKAS), ISO9001:2000, Link-Up, and ISO13485:2003. In addition, the company is subject to a range of external and internal quality assurance programmes.
Our strategy
Concateno’s goal is to be the top provider of drug and alcohol testing services in the world, providing the best expertise and testing resources in the field. With our own best-in-class products and facilities that can supply across the whole range of test requirements, our strategy is driven by customer need rather than product benefit.
Concateno has committed significant investment to research and development. Our joint development agreement with Philips (a diversified health and wellbeing company) to develop a new oral fluids system is an example of this commitment.
Excellent pedigree
Concateno is built upon the consolidation of Europe’s strongest and most expert drug testing companies:
Cozart: long-established expertise in oral fluid instant testing (including its pioneering Rapiscan® and DDS® reader devices) and the manufacture of laboratory Reagents and products – largely through its wholly-owned subsidiary Spinreact, headquartered in Spain
Medscreen: Europe’s most experienced workplace testing company with a 20 year track record in providing legally defensible urine testing to employees and the UK government
Altrix Healthcare: largest provider of oral fluids drugs of abuse laboratory testing to the UK healthcare market. Complemented with a blood-borne virus testing service and range of support services focused on client treatment needs
TrichoTech: Europe’s largest hair testing laboratory with unrivalled knowledge and expertise
Euromed: supplies a comprehensive range of point-of-collection testing devices with a proven track record on quality assurance and technical support, underscored by its long-standing contract with HM Prison Service
Concateno
New Biologic STELARA(TM) Receives Approval In Europe For Treatment Of Moderate To Severe Plaque Psoriasis
Janssen-Cilag announced that STELARA(TM) (ustekinumab), the first in a new class of biologics, has been approved by the European Commission for use across Europe. The approved indication of ustekinumab is for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA (psoralen plus ultraviolet A light). With the approval by the European Commission, ustekinumab is approved in 27 countries in the EU. Psoriasis, a chronic skin disease that affects between two and three percent of the European population,(1) is associated with substantial physical and emotional burdens and potentially serious co-morbidities.(2,3)
In clinical studies, treatment with ustekinumab demonstrated significant improvements in patients’ psoriasis, and quality of life, which were sustained with as few as four injections a year (every twelve weeks) following two starter doses at weeks 0 and 4. The approval of ustekinumab offers adults living with moderate-to-severe plaque psoriasis a new therapy which has the potential to make a considerable impact on their daily lives.
The approval is based on data from two large, pivotal Phase III, multi-centre, randomised, double-blind, placebo controlled trials (PHOENIX 1 & 2) involving nearly 2,000 patients in whom the efficacy and safety of ustekinumab in the treatment of moderate-to-severe plaque psoriasis were evaluated.(4,5) Two-thirds or more of patients achieved the primary endpoint of each trial, at least 75% improvement in psoriasis using the Psoriasis Area and Severity Index (PASI 75) at week 12, after receiving just two doses of ustekinumab 45 mg or 90 mg, respectively, at weeks 0 and 4. At week 12, 66 percent to 76 percent of patients receiving ustekinumab 45 mg or 90 mg doses, respectively, achieved PASI 75 compared with 3 to 4 percent of patients receiving placebo (p
Rates of serious adverse events, including serious infections, malignancies and cardiovascular events, were low and consistent with the expected background rates. The most common adverse reactions in Phase III clinical trials were arthralgia, cough, headache, injection site erythema, nasopharyngitis and upper respiratory tract infection. Most were considered to be mild and did not necessitate discontinuation of therapy.
About Psoriasis
Psoriasis is a chronic, immune-mediated inflammatory disease, which results from the over-production of skin cells resulting in their accumulation on the surface of the skin, which causes red, scaly plaques that may itch and bleed. It is estimated that between two and three percent of the European population have psoriasis.(1) Twenty to thirty percent of people with psoriasis have cases that are considered severe.(6)
About STELARA (ustekinumab)
Ustekinumab is a new, human monoclonal antibody with a novel mechanism of action that targets the p40 sub-unit of cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in regulating immune responses and that are thought to be associated with some immune-mediated inflammatory disorders, including plaque psoriasis. In the United States, the Biologics License Application (BLA) for ustekinumab is under regulatory review by the U.S. Food and Drug Administration (FDA).
Centocor Ortho Biotech Inc. discovered STELARA and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies have exclusive marketing rights in all countries outside of the United States.
Important Safety Information
STELARA is a selective immunosuppressant and may have the potential to increase the risk of infections and reactivate latent infections. Serious infections have been observed in patients receiving STELARA in clinical trials. Do not start STELARA during an active infection. If a serious infection develops, monitor patients carefully and stop STELARA until the infection resolves. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment with STELARA.
STELARA is a selective immunosuppressant. Immunosuppressive agents have the potential to increase the risk of malignancy. Malignancies have been observed in patients receiving STELARA in clinical trials. Caution should be exercised when considering the use of STELARA in patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.
References
1. Schafer T. Epidemiology of Psoriasis; Review and the German Perspective. Dermatology. 2006;212:327-337.
2. Dubertret L, Mrowietz U, Ranki A, et al. European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol. 2006;155(4):729-736.
3. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol. 1995;32(6):982-986.
4. Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). The Lancet. 2008;371:1665-74.
5. Papp K, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). The Lancet. 2008;371:1675-84.
6. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005. Br J Dermatol. 2005;153(3):486-497.
Janssen-Cilag
http://www.janssen-cilag.com
Genaera Presents Promising Preclinical Data For Trodusquemine (MSI-1436) At Keystone Symposia
Genaera Corporation (Nasdaq: GENR) announced a poster presentation of preclinical data on trodusquemine (MSI-1436), Genaera’s lead drug candidate for the treatment of type 2 diabetes and obesity, during the Keystone Symposia: Obesity – Novel Aspects of the Regulation of Body Weight in Banff, Alberta.
The poster entitled “Effect of MSI-1436 (Trodusquemine) on Body Weight and Metabolic Profile in Diet-Induced Obese Rats” concluded that a single subcutaneous dose of MSI-1436 leads to marked reductions in body weight, fasting blood glucose, serum triglycerides and cholesterol in diet-induced obese (DIO) rats. In the study, the researchers reported that MSI-1436 induced dose-dependent changes in daily food intake resulting in corresponding decreases in body weight, as well as marked improvements in glucose tolerance and lipid profile.
“The DIO rat is a standard and well-accepted preclinical model for demonstrating anti-obesity impact in this class of drugs. These initial subcutaneous studies of MSI-1436 exhibit dose-related reductions across a wide range of clinical and metabolic outcomes associated with both obesity and diabetes,” commented Jack Armstrong, President and CEO of Genaera. “We are continuing to progress the subcutaneous formulation and are planning our initial human studies with MSI-1436 via this route later this year.”
About Trodusquemine (MSI-1436)
Trodusquemine is the first highly selective inhibitor of protein tyrosine phosphatase 1B (PTP1B), an enzyme central to controlling the function of both the leptin and insulin pathways. By inhibiting both central and peripheral PTP1B, MSI-1436 is expected to decrease appetite and normalize blood sugar. Initial clinical studies of trodusquemine in obese and overweight subjects has provided early indicators of weight loss and improved glucose control. These results confirm previous work in animal models which demonstrated significant weight loss without metabolic rebound, which often limits sustained weight loss during caloric restriction. In addition, trodusquemine has shown the ability to reverse co-morbidities associated with obesity such as abnormal glucose metabolism and cholesterol elevation.
About Genaera
Genaera Corporation is developing trodusquemine (MSI-1436), for type 2 diabetes and obesity currently in phase 1 clinical testing and has a fully out-licensed partnership with MedImmune, Inc. that is in phase 2 clinical testing in asthma. For further information, please see our website at http://www.genaera.com.
This announcement contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks and uncertainties, known and unknown. Forward-looking statements reflect management’s current views and are based on certain expectations and assumptions. You may identify some of these forward-looking statements by the use of words in the statements such as “anticipate,” “believe,” “continue,” “develop,” “expect,” “plan” and “potential” or other words of similar meaning. Genaera’s actual results and performance could differ materially from those currently anticipated and expressed in these and other forward-looking statements as a result of a number of risk factors, including, but not limited to the risks and uncertainties discussed in Genaera’s filings with the U.S. Securities and Exchange Commission, all of which are available from the Commission in its EDGAR database at http://www.sec.gov as well as other sources. You are encouraged to read these reports. Given the uncertainties affecting development stage pharmaceutical companies, you are cautioned not to place undue reliance on any such forward-looking statements, any of which may turn out to be wrong due to inaccurate assumptions, unknown risks, uncertainties or other factors. Genaera does not intend (and it is not obligated) to publicly update, revise or correct these forward-looking statements or the risk factors that may relate thereto.
Genaera Corporation
http://www.genaera.com
Meritage Pharma Initiates Phase 2b Clinical Trial Of Oral Viscous Budesonide For Pediatric Patients With Eosinophilic Esophagitis
Meritage Pharma, Inc. announced that it has initiated a dose-ranging Phase 2b clinical trial to evaluate oral viscous budesonide (OVB) for the treatment of children and adolescents with eosinophilic esophagitis (EoE), an allergic inflammatory condition of the esophagus. EoE can cause difficulty in swallowing and heartburn, and in severe cases it can lead to food impaction (food getting stuck in the esophagus) and in children, a failure to thrive (poor growth or weight loss). The trial is being conducted at multiple U.S. clinical centers that specialize in the treatment of patients with gastrointestinal diseases.
EoE is an emerging disease that has only recently been classified as a separate condition. Most centers of excellence have seen a dramatic rise in the incidence and diagnosis of EoE over the last decade. EoE tends to be a chronic disease with persistent or relapsing symptoms. The disease occurs when eosinophils, a type of white blood cell involved in allergic reactions, infiltrate the surface of the esophagus. This eosinophil infiltration leads to inflammation of the esophagus and is believed to cause the symptoms of EoE. A variety of stimuli may trigger this allergic process including certain foods and environmental allergens. People with EoE commonly have other allergic conditions such as asthma or eczema.
Symptoms of EoE may include nausea, dysphagia (problems swallowing), vomiting, stomach pain, chest pain, heartburn, loss of weight, and food impaction. Other symptoms may include reflux that does not respond to proton pump inhibitor therapy, failure to thrive, poor appetite, malnutrition and difficulty sleeping.
The double-blind, randomized, placebo-controlled 12-week study in up to 80 patients with confirmed EoE aged two to 18 is designed to evaluate three different doses of OVB. Patients will be evaluated by performing biopsies of the esophagus obtained before and after OVB administration as well as their symptomatic response to therapy.
“There has been tremendous interest in Meritage Pharma’s OVB clinical trial due to the increasing number of EoE diagnoses and the lack of an approved therapy for EoE,” states Malcolm R. Hill, Pharm.D., chief scientific officer of Meritage Pharma, Inc. “Patients with EoE struggle with apparent allergies to many foods and other allergens, and it is often difficult to eliminate possible symptom triggers. Meritage Pharma is eager to evaluate OVB as a potential therapy to enable patients to thrive, despite their disease.”
OVB is a proprietary oral formulation of budesonide. Budesonide is the active pharmaceutical ingredient in several products approved by the U.S. Food and Drug Administration (FDA), including products for the treatment of pediatric asthma, allergic rhinitis and Crohn’s disease. Budesonide is a corticosteroid and has an established safety profile in those diseases. It works by decreasing inflammation in the treated area. Meritage Pharma’s proprietary formulation is viscous and is designed to coat the esophagus with budesonide where it can act locally.
The FDA has granted Orphan Drug Status designation to OVB for the treatment of pediatric EoE. FDA designation generally provides Meritage Pharma with market exclusivity for the product for seven years following FDA approval, in addition to other incentives.
About Meritage Pharma
Meritage Pharma is committed to the development of prescription products based on safe and effective molecules for the treatment of gastrointestinal and atopic diseases. Meritage Pharma’s initial product candidate is intended for the treatment of pediatric eosinophilic esophagitis, an allergic inflammation of the gastrointestinal tract and is currently in a Phase 2b study. The management team has an established track record of building successful specialty pharmaceutical companies and in identifying and developing novel products for atopic diseases. The company was founded in March 2008 and has raised over $22.5 million in Series A financing from Domain Associates, Latterell Venture Partners and The Vertical Group. More information about Meritage Pharma is available at http://www.meritagepharma.com.
Meritage(TM) is a trademark of Meritage Pharma, Inc
Forward-Looking Statements
Meritage Pharma cautions you that statements included in this press release that are not a description of historical facts may be forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Meritage Pharma that any of its plans will be achieved. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in Meritage Pharma’s business including, without limitation, statements about: difficulties or delays in developing, obtaining regulatory approval, manufacturing and commercializing its products; unexpected performance or side effects of its products that could delay or prevent development or commercialization; the scope and validity of patent protection for its products; competition from other pharmaceutical companies; and its ability to obtain additional financing to support its operations. All forward-looking statements are qualified in their entirety by this cautionary statement and Meritage Pharma undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.
Meritage Pharma, Inc.
http://www.meritagepharma.com
The Leukemia & Lymphoma Society And Celator Pharmaceuticals Announce Partnership To Accelerate Development Of CPX-351 For AML
The Leukemia & Lymphoma Society (LLS) and Celator Pharmaceuticals, Inc. announced a partnership to support Phase 2 development of Celator’s lead product candidate CPX-351 (Cytarabine:Daunorubicin) Liposome Injection for treatment of adults with acute myeloid leukemia (AML).
Through the partnership, LLS will provide $3.7 million to support Celator’s Phase 2B multicenter, randomized, open-label trial of CPX-351 versus intensive salvage therapy in adult patients less than or equal to 60 years of age with AML in first relapse. Celator expects to start patient enrollment in this study in the first quarter of 2009 in the United States and Canada.
The partnership between Celator and LLS is part of LLS’s Therapy Acceleration Program (TAP), which supports private sector and academic-based projects with the goal of advancing investigational therapies with high prospects for providing near-term benefit to patients with blood cancers.
“Celator has discovered a novel way to deliver and enhance the activity of agents that have been the standard of care in AML for decades,” said Louis DeGennaro, Ph.D., LLS’s chief scientific officer. “There have been many attempts to improve outcomes in this patient population with little success. The data collected on CPX-351 to date, and the enthusiasm of clinical investigators involved in that research, suggest that Celator’s approach holds real promise to advance the treatment of AML.”
“We are very pleased that The Leukemia & Lymphoma Society sees the potential of CPX-351 and is making this substantial investment,” said Scott Jackson, chief executive officer, Celator Pharmaceuticals. “LLS has created a well defined, streamlined process for accessing capital for promising new blood cancer treatments. This commitment enhances our ability to further the clinical development of CPX-351 in patients with AML.”
About CPX-351
CPX-351 represents a new approach to developing combinations of drugs in which drug molar ratios with synergistic anti-tumor activity are encapsulated in a drug delivery vehicle in order to maintain the desired ratio following administration. CPX-351 has been granted orphan drug status by the U.S. Food & Drug Administration (FDA) for the treatment of AML and is currently being studied in a randomized trial comparing CPX-351 versus conventional cytarabine and daunorubicin therapy (“7+3″) in patients 60-75 years of age with untreated AML.
About Acute Myeloid Leukemia (AML)
The National Cancer Institute defines AML as a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow. In 2008, the American Cancer Society’s Cancer Facts and Figures estimates 13,290 new cases of AML and 8,820 deaths.
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society(R), headquartered in White Plains, NY, with 68 chapters in the United States and Canada, is the world’s largest voluntary health organization dedicated to funding blood cancer research and providing education and patient services. LLS’s mission: Cure leukemia, lymphoma, Hodgkin’s disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, LLS has invested more than $600 million in research specifically targeting leukemia, lymphoma and myeloma. Last year alone, LLS made 6.3 million contacts with patients, caregivers and healthcare professionals.
About Celator
Celator(R) Pharmaceuticals, Inc., with locations in Princeton, NJ, and Vancouver, BC, is a privately held pharmaceutical company developing new and more effective therapies to treat cancer. CombiPlex(R), the company’s drug ratio technology platform, represents a novel approach that identifies molar ratios of drugs that will deliver a synergistic benefit, locks the desired ratio in a drug delivery vehicle that maintains the ratio in patients with the goal of improving clinical outcomes. The company pipeline includes: CPX-351 (a liposomal formulation of cytarabine:daunorubicin), currently in Phase 2 in patients with acute myeloid leukemia; CPX-1 (a liposomal formulation of irinotecan:floxuridine), currently in Phase 2 in patients with colorectal cancer; CPX-571 (a liposomal formulation of irinotecan:cisplatin), a preclinical stage compound; and multiple research programs. Based on the applications of CombiPlex, Celator is positioned to advance a broad pipeline of combination therapies involving both previously approved and novel drug agents. For more information, please visit the company’s website at http://www.celatorpharma.com.
Celator Pharmaceuticals, Inc.
http://www.celatorpharma.com
The Leukemia & Lymphoma Society And Celator Pharmaceuticals Announce Partnership To Accelerate Development Of CPX-351 For AML
The Leukemia & Lymphoma Society (LLS) and Celator Pharmaceuticals, Inc. announced a partnership to support Phase 2 development of Celator’s lead product candidate CPX-351 (Cytarabine:Daunorubicin) Liposome Injection for treatment of adults with acute myeloid leukemia (AML).
Through the partnership, LLS will provide $3.7 million to support Celator’s Phase 2B multicenter, randomized, open-label trial of CPX-351 versus intensive salvage therapy in adult patients less than or equal to 60 years of age with AML in first relapse. Celator expects to start patient enrollment in this study in the first quarter of 2009 in the United States and Canada.
The partnership between Celator and LLS is part of LLS’s Therapy Acceleration Program (TAP), which supports private sector and academic-based projects with the goal of advancing investigational therapies with high prospects for providing near-term benefit to patients with blood cancers.
“Celator has discovered a novel way to deliver and enhance the activity of agents that have been the standard of care in AML for decades,” said Louis DeGennaro, Ph.D., LLS’s chief scientific officer. “There have been many attempts to improve outcomes in this patient population with little success. The data collected on CPX-351 to date, and the enthusiasm of clinical investigators involved in that research, suggest that Celator’s approach holds real promise to advance the treatment of AML.”
“We are very pleased that The Leukemia & Lymphoma Society sees the potential of CPX-351 and is making this substantial investment,” said Scott Jackson, chief executive officer, Celator Pharmaceuticals. “LLS has created a well defined, streamlined process for accessing capital for promising new blood cancer treatments. This commitment enhances our ability to further the clinical development of CPX-351 in patients with AML.”
About CPX-351
CPX-351 represents a new approach to developing combinations of drugs in which drug molar ratios with synergistic anti-tumor activity are encapsulated in a drug delivery vehicle in order to maintain the desired ratio following administration. CPX-351 has been granted orphan drug status by the U.S. Food & Drug Administration (FDA) for the treatment of AML and is currently being studied in a randomized trial comparing CPX-351 versus conventional cytarabine and daunorubicin therapy (“7+3″) in patients 60-75 years of age with untreated AML.
About Acute Myeloid Leukemia (AML)
The National Cancer Institute defines AML as a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow. In 2008, the American Cancer Society’s Cancer Facts and Figures estimates 13,290 new cases of AML and 8,820 deaths.
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society(R), headquartered in White Plains, NY, with 68 chapters in the United States and Canada, is the world’s largest voluntary health organization dedicated to funding blood cancer research and providing education and patient services. LLS’s mission: Cure leukemia, lymphoma, Hodgkin’s disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, LLS has invested more than $600 million in research specifically targeting leukemia, lymphoma and myeloma. Last year alone, LLS made 6.3 million contacts with patients, caregivers and healthcare professionals.
About Celator
Celator(R) Pharmaceuticals, Inc., with locations in Princeton, NJ, and Vancouver, BC, is a privately held pharmaceutical company developing new and more effective therapies to treat cancer. CombiPlex(R), the company’s drug ratio technology platform, represents a novel approach that identifies molar ratios of drugs that will deliver a synergistic benefit, locks the desired ratio in a drug delivery vehicle that maintains the ratio in patients with the goal of improving clinical outcomes. The company pipeline includes: CPX-351 (a liposomal formulation of cytarabine:daunorubicin), currently in Phase 2 in patients with acute myeloid leukemia; CPX-1 (a liposomal formulation of irinotecan:floxuridine), currently in Phase 2 in patients with colorectal cancer; CPX-571 (a liposomal formulation of irinotecan:cisplatin), a preclinical stage compound; and multiple research programs. Based on the applications of CombiPlex, Celator is positioned to advance a broad pipeline of combination therapies involving both previously approved and novel drug agents. For more information, please visit the company’s website at http://www.celatorpharma.com.
Celator Pharmaceuticals, Inc.
http://www.celatorpharma.com
ISTA Pharmaceuticals Announces Positive Results For Phase IIb Study Of Ecabet Sodium
ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA), announced positive results from the Company’s Phase IIb clinical study of ecabet sodium, which is being developed as a treatment for dry eye disease. Patients treated with ecabet sodium achieved a strong positive trend in the objective sign of Tear Film Break-Up Time (TFBUT) and a positive trend in the objective sign of quantity of tears produced (Schirmer Test). In contrast, there were no trends seen in the placebo group for either objective sign. In addition, there were no trends seen in either group in subjective symptoms as measured by the Ocular Surface Disease Index (OSDI) or patient’s worst reported symptom. In Phase II tests where observations are not powered to show statistical significance, strong and positive trends are used as indicators of potential efficacy in subsequent Phase III studies.
“The Phase IIb results from this environmental study add further support to our belief that ecabet sodium has the ability to treat signs and symptoms of dry eye syndrome. Ecabet sodium may provide advantages over other products used to treat dry eye and those that are in development, as we believe ecabet sodium not only improves the quality of tears but also increases the quantity of tears,” stated Vicente Anido Jr., Ph.D., President and Chief Executive Officer of ISTA Pharmaceuticals. “After reviewing the guidance from and our discussions with the FDA, we believe that by conducting two successful Phase III environmental clinical trials for improvement in signs and two successful Phase III controlled chamber clinical trials for the improvement of symptoms, we should receive marketing approval. In addition, we are expecting results from a Phase II clinical trial studying the potential of a lower strength of Xibrom to treat the signs and symptoms of dry eye disease in the first half of 2009. Once this lower strength Xibrom trial is completed, we will make a decision on which product or products in our dry eye franchise to move into Phase III trials, which could start as early as 2010.”
ISTA’s previous two Phase II trials of ecabet, which were conducted in a controlled environment chamber, demonstrated positive trends in patient’s symptoms (OSDI and patient’s worst symptom, both trials) and in the signs of corneal staining (one trial) and blink rate (both trials). The Company believes the lack of response to ecabet in symptoms in the most recent trial is not of concern, in part because the OSDI responses to ecabet sodium were strong and predictable in the previous Phase II trials. ISTA believes that given the ability to demonstrate a positive effect on signs in the environment and on symptoms in the controlled environment chamber, there is now a clear path forward to Phase III studies and New Drug Application filing for this product.
Background on ISTA’s Recent Phase IIb Study Results
ISTA’s Phase IIb trial randomized 144 patients to receive either ecabet sodium or placebo four times per day for 43 days. The object of the study was to investigate ecabet sodium’s effects on the objective signs of tear production (Anesthetized and Unanesthetized Schirmer Tests) and tear film quality (TFBUT) and subjective symptoms (OSDI, patient’s worst symptom) in patients with dry eye disease when administered under normal environmental conditions.
In the analysis of responders to both ecabet sodium and placebo, results of the Anesthetized Schirmer Test in the Phase IIb study revealed a strong trend for ecabet sodium, which approached statistical significance versus placebo. This result is important because it indicates an effect on basal tear secretion, which is one of the main factors in the etiology of dry eye disease. In addition, the percentage of patients who responded to ecabet sodium was greater than that seen in the trials that led to the approval of the only currently approved product on the market for dry eye disease. Further, this trend in increased Schirmer Test score was seen as early as day 22 of treatment and continued to trend upwards through day 43. Adverse events were uncommon and similar between the treatment and placebo groups, and there were no serious ocular or systemic adverse events.
Another important finding in this trial was that patients with more severe disease as measured by the Anesthetized Schirmer Test, TFBUT and specific staining attributes were more likely to respond to ecabet sodium than placebo. Thus, in future Phase III trials, these specific attributes can be used for screening of patients who would be most likely to benefit from treatment with ecabet sodium.
About Ecabet Sodium
ISTA acquired U.S. rights to ecabet sodium for the treatment of dry eye syndrome from Senju Pharmaceuticals Co., Ltd., in November of 2004. Ecabet sodium is already marketed in Japan as an oral agent for gastric ulcers and gastritis by Mitsubishi Tanabe Pharma Corporation (formerly Tanabe Seiyaku Co., Ltd.) as an originator of ecabet sodium.
Ecabet sodium represents a new class of molecules that increase the quantity of mucin produced by conjunctival goblet cells and corneal epithelia. Mucin is a glycoprotein component of tear film that lubricates while retarding moisture loss from tear evaporation.
About ISTA Pharmaceuticals
ISTA Pharmaceuticals is an ophthalmic pharmaceutical company. ISTA’s products and product candidates addressing the $4.7 billion U.S. prescription ophthalmic industry include therapies for inflammation, ocular pain, glaucoma, allergy, and dry eye. The Company currently markets three products and is developing a strong product pipeline to fuel future growth and market share, thereby continuing its growth to become the leading niche ophthalmic pharmaceutical company in the U.S. For additional information regarding ISTA, please visit ISTA Pharmaceuticals’ website at http://www.istavision.com.
Any statements contained in this press release referring to future events or other non-historical matters are forward-looking statements. Without limiting the foregoing, but by way of example, statements contained in this press release related to the anticipated design of future ecabet sodium studies, the results of future or ongoing studies with lower strength Xibrom, ISTA’s intention to select one or more products to advance to Phase III in 2010, ISTA’s belief that ecabet sodium not only improves the quality of tears but also increases the quantity of tears, ISTA’s belief that conducting two successful Phase III environmental clinical trials for improvement in signs and two successful Phase III controlled chamber clinical trials for the improvement of symptoms should lead to marketing approval of ecabet sodium and ISTA’s expectation of becoming the leading niche ophthalmic pharmaceutical company are forward-looking statements. Except as required by law, ISTA disclaims any intent or obligation to update any forward-looking statements. These forward-looking statements are based on ISTA’s expectations as of the date of this press release and are subject to risks and uncertainties that could cause actual results to differ materially. Important factors that could cause actual results to differ from current expectations include, among others, delays and uncertainties related to the FDA or other regulatory agency approval or actions; the uncertain nature of clinical research and uncertainties and risks regarding market acceptance of and demand for ISTA’s approved products; and such other risks and uncertainties as detailed from time to time in ISTA’s public filings with the U.S. Securities and Exchange Commission, including but not limited to ISTA’s Annual Report on Form 10-K for the year ended December 31, 2007, and its most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2008.
ISTA Pharmaceuticals, Inc.
http://www.istavision.com
Light Alcohol May Reduce Disability In Healthy Seniors
A new US study found that light to moderate alcohol consumption may reduce the risk of physical disabilities that cause so may seniors to lose
their independence, but this was only the case for healthy older adults, the researchers found no benefit for those in poor health.
The study was the work of lead author, Dr Arun S. Karlamangla, an associate professor of medicine at the David Geffen School of Medicine,
University of California, Los Angeles, and colleagues, and is published in the 1 January 2009 print issue of the American Journal of
Epidemiology.
Some studies have already shown that light to moderate alcohol consumption is linked to lower risk of heart disease, diabetes and death. Karlamangla
and colleagues wanted to investigate if this might be the same for physical disability, such as that which impedes the older person from doing essential
everyday things like getting dressed, preparing and eating meals, going shopping, walking, and so on.
For the study they looked at the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study surveys from 1982
to 1992 and used data for two 5-year periods relating to 4,276 non-institutionalized US adults who were aged 50 or more.
They found that compared to heavy drinking, or not drinking at all, light to moderate drinking (ie fewer than 15 drinks a week with no more than 5 in a
day for men and 4 for women) was linked with a nearly 25 per cent reduced risk of incident disability or death over 5 years.
When they investigated further, by looking at self-reported health status, they found that disability risk went down the more the participants drank, up
to the light to moderate limit, but this was only the case for those who reported being in good or better health, it was not the case for those who
reported being in fair or worse health.
Karlamangla and colleagues concluded that:
“Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor
health.”
Karlamanga told HealthDay of ScoutNews, LLC, that what this finding says to those seniors who only drink a light to moderate amount of
alcohol is:
“Don’t worry, you’re probably in good company, and you’re probably going to get good benefits from this.”
But he added that “if your health is not good, you probably should not be drinking”.
Speculating on the reasons why the not so healthy participants showed no benefit, co-author Dr Alison A Moore, from the David Geffen School of
Medicine, where she is a professor specializing in geriatric medicine, said it could be that alcohol has a bad effect on medications, or that their poor
health was irreversible.
She said the usual recommendation for the older adult was one drink a day, but these findings show there are healthy seniors who can drink more than
this.
“Light to Moderate Alcohol Consumption and Disability: Variable Benefits by Health Status.”
Arun S. Karlamangla, Catherine A. Sarkisian, Deborah M. Kado, Howard Dedes, Diana H. Liao, Sungjin Kim, David B. Reuben, Gail A. Greendale,
and Alison A. Moore.
Am. J. Epidemiol., 1 January 2009; 169: 96 – 104.
doi:10.1093/aje/kwn294
Click here for Abstract.
Sources: Journal Article, HealthDay of ScoutNews, LLC.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
US Approves First Trial Of Embryonic Stem Cells
The US regulators have given the go ahead for a biotech company to carry out the world’s first trial of a treatment using embryonic stem cells, in
this case to treat victims of spinal cord injury that leaves them unable to walk.
Although heralded as an early sign of new US president Obama’s support for embryonic stem cell research, Dr Thomas Okarma, president and CEO of
Geron Corp. of Menlo Park, California, the company that will be carrying out the trial, told Associated Press that strictly speaking it was not so in this
case, since the next phase of the project would have been eligible for federal funds under Bush. It was the earlier development phases that had to
be done with private funds because of funding restrictions on embryonic stem cell research brought in by Bush in 2001, said a report in Times
Online.
Today’s ruling by the US Food and Drug Administration (FDA) allows Geron to give 8 to 10 patients with spinal cord injury a single injection of
cells made from embryonic stem cells. The testing will be done at several medical centres throughout the US and the patients will receive their
injections within 2 weeks of their injury; unfortunately patients whose injuries are older than this are unlikely to benefit from such therapy.
According to a Geron statement, the Phase I trial is designed to establish the safety of the treatment, called GRNOPC1, in patients with “complete”
American Spinal Injury Association (ASIA) grade A subacute thoracic spinal cord injuries.
Okarma told AP that they will also be looking for the possible return of feeling or movement in the legs. Animal studies have shown that injected
embryonic stem cells can turn into specialist cells that replace damaged sheaths around nerves that have suffered “demyelination” and thereby restore
their ability to send signals that control muscle and sense feelings.
Embryonic stem cells are like master cells, they can become virtually any cell of the body, which comprises about 200 types of tissue. There are other
kinds of stem cells too, like adult stem cells, but they are more limited in what types of cell they can become and harder to “coax”, so embryonic stem cells are considered
the “gold standard” in stem cell research. They are however more controversial because harvesting them involves destroying embryos, whereas adult
stem cells can be recovered without harming the donor.
If successful, the trial will lead to therapies with the potential to transform the lives of thousands of people who every year become paralysed from the
chest down, and for whom few treatments exist. Experts predict that if successful, the therapy could be in general use within three to five
years.
Okarma said in a press statement that:
“This marks the beginning of what is potentially a new chapter in medical therapeutics — one that reaches beyond pills to a new level of healing: the
restoration of organ and tissue function by the injection of healthy replacement cells.”
He said that: “the ultimate goal is to achieve restoration of spinal cord function”.
Although the FDA decision is independent of the White House, it is being received as a symbol of a new attitude to embryonic stem cell research and
Obama is expected to start lifting funding restrictions next week, said a Times Online report.
Dr Richard Fessler, professor of neurological surgery at the Feinberg School of Medicine at Northwestern University, said that:
“The neurosurgical community is very excited by this new approach to treating devastating spinal cord injury.”
“Demyelination is central to the pathology of the injury, and its reversal by means of injecting oligodendrocyte progenitor cells would be revolutionary
for the field. If safe and effective, the therapy would provide a viable treatment option for thousands of patients who suffer severe spinal cord injuries
each year,” he added.
Polling figures suggest most Americans are in favour of stem cell research, but it was strong opposition lobbying that persuaded Bush to impose
restrictions on federal funding.
Okarma said that the delay caused by the funding restriction meant there “are people out there who might have benefited, but who now cannot,” he told the press.
Sources: Times Online, Associated Press, Geron.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
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