|
|
Post by GodFather on Sept 24, 2013 14:37:27 GMT 5.5
Targeting memory T-cells in Type 1 diabetes
Encouraging results from the T1DAL study (Targeting effector memory T cells with alefacept in new onset type 1 diabetes), led by Mark R. Rigby M.D., Ph.D. from Indiana University and Riley Hospital for Children in Indianapolis and sponsored by the Immune Tolerance Network (ITN) with additional support from JDRF, are published in The Lancet Diabetes & Endocrinology.
Alefacept, an engineered fusion protein targeting a surface molecule, CD2, found on T-lymphocytes, was the first biologic therapy approved for moderate to severe plaque psoriasis. By binding CD2, alefacept inhibits co-stimulation and induces T-cell depletion. T-cell mediated destruction of insulin producing pancreatic beta cells is a central feature of Type 1 diabetes, but targeting of CD2 has not previously been evaluated in this disease. The T1DAL trial was designed to test whether alefacept would preserve pancreatic beta cell function in newly diagnosed patients.
The Phase II T1DAL study enrolled 49 new-onset type 1 diabetic subjects, ages 12 to 35, who were randomized into two groups: 33 to alefacept and 16 to placebo. Patients received two twelve week courses (separated by a 12 week pause) of either alefacept or placebo. Twelve months from the start of the study, patients underwent a mixed meal tolerance test to measure the C-peptide response (a measure of insulin production). The primary endpoint, a 2-hour C-peptide response, did not show statistically significant differences between treatment and placebo groups; however, a secondary endpoint, a 4-hour C-peptide response, was significantly higher at 12 months in the treatment group compared to the placebo group. Other secondary endpoints including insulin use and rate of hypoglycemic events were significantly lower at 12 months in the alefacept treated group.
Although the primary endpoint was not met, these encouraging results of key secondary endpoints suggest a disease-modifying effect of alefacept. Additional support for alefacept's therapeutic role comes from analysis of T-cell subtypes of treated patients that showed that effector T cells were primarily targeted while sparing protective regulatory T cells. Lead investigator Dr. Mark Rigby suggests, "The T1DAL study is the first to use an agent to specifically deplete the cells which attack the pancreas in type 1 diabetes, the memory and effector T cells. We also found that regulatory T cells are not depleted with this therapy, suggesting that immune re-education can take place."
Longer 24 month follow-up of the subjects in this study is in progress to evaluate the potential for durable efficacy of the alefacept treatment. "Unfortunately our study was not able to enroll the goal number of participants due to drug availability which prevented more definitive conclusions at this point," said Dr. Rigby. "We are eagerly awaiting additional data over the next year which will help us determine if targeting memory T cells will help those with Type 1 diabetes make insulin for extended periods."
About The Immune Tolerance Network
The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system.
|
|
|
|
Post by GodFather on Sept 24, 2013 14:39:17 GMT 5.5
Malaria No More and Novartis launch Power of One, a global digital fundraising campaign to help eliminate malaria deaths
Novartis and Malaria No More announced today the debut of the Power of One campaign, encouraging people around the world to help end child deaths from malaria. Novartis will support the campaign financially and donate up to three million Coartem® Dispersible treatments to match antimalarials funded by the public. The company's commitment to Power of One aligns with its long history in the fight against malaria; the Novartis Malaria Initiative is one of the largest access-to-medicine programs in the healthcare industry.
Malaria is a preventable and treatable disease, but it still kills a child every minute. It is estimated that over 300 million additional treatments will be needed to treat malaria patients across Africa between now and the end of 2015. The Power of One campaign aims to address this treatment gap through direct donations and existing government commitments. Every dollar donated to the campaign will buy and deliver a treatment to a child diagnosed with malaria.
"I am proud of the significant and longstanding commitment Novartis has to the fight against malaria. For all our progress though, there's still more work to do" said Joseph Jimenez, CEO of Novartis. "We need more help to close the treatment gap and Power of One offers everyone a chance to engage and make a difference for children suffering from malaria."
Harnessing social, mobile, and e-commerce technologies, Power of One enables the public to purchase a treatment and track the journey of a treatment. Donors will be able to see the effect of their donation on the ground, share information with their networks and recruit other donors.
"It's unacceptable that a child dies every minute for lack of a dollar's worth of treatment," said Martin EdL@#d, CEO, Malaria No More. "We're urging the world to join the Power of One campaign and to donate and engage their friends in this fight."
Novartis is the exclusive treatment sponsor of the Power of One campaign, joining some of the world's most innovative companies. Additional sponsors include Alere Inc., which will provide malaria rapid diagnostic tests, 21st Century Fox, AHAlife.com, Causes.com, Time Warner, Twitter, Venmo and others. Zambia will be the first country to receive deliveries of treatments and tests as a result of the Power of One campaign.
Novartis reaches 200 million deliveries of Coartem® Dispersible
Since 2009, Novartis has delivered 200 million treatments of its pediatric antimalarial Coartem® Dispersible without profit to more than 50 malaria-endemic countries. Never before have so many pediatric treatments been distributed in such a short time frame for children suffering from malaria. The 200 millionth treatment was delivered to Zambia, which also received the first consignment of Novartis treatments for the Power of One campaign, raised during World Malaria Day on April 25, 2013.
"MMV applauds Novartis on this laudable achievement," said David Reddy, CEO of Medicines for Malaria Venture. "Novartis has done a tremendous job of bringing an innovative drug to the vulnerable young victims of malaria in Zambia and over 50 other countries, giving it global reach. We at MMV are proud to have partnered with Novartis on the development of this important formulation."
The Novartis Malaria Initiative is one of the largest access-to-medicine programs in the healthcare industry. Moving forward, Novartis is committed to malaria elimination by driving the development of the next generation antimalarials, with two new classes of anti-malaria drugs currently in development. The most advanced compound is in Phase II clinical trials.
About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world.
|
|
|
|
Post by GodFather on Sept 25, 2013 18:39:59 GMT 5.5
Warning of potential side effects of a product can increase its sales
Drug ads often warn of serious side effects, from nausea and bleeding to blindness, even death. New research suggests that, rather than scaring consumers away, these warnings can improve consumers' opinions and increase product sales when there is a delay between seeing the ad and deciding to buy or consume the product.
"Messages that warn consumers about potentially harmful side effects - presumably with the intent to nudge them to act more cautiously - can ironically backfire," says psychological scientist Ziv Carmon of INSEAD in Singapore.
Working with Yael Steinhart of Tel Aviv University and Yaacov Trope at New York University, Carmon has been exploring how adding a warning of potential side effects affects consumer decision making. Their new findings are published in the September 2013 issue of Psychological Science, a journal of the Association for Psychological Science.
"We were struck by just how detailed, clear, and scary many warnings had become with regard to potential negative side-effects of products," says Carmon. "It then occurred to us that such warnings might perversely boost rather than detract from the appeal of the risky product."
Carmon and colleagues tested their hypothesis in four experiments. In one experiment, for example, smokers saw an ad for a brand of cigarettes: one version of the ad included a warning that smoking causes lung cancer, heart disease, and emphysema, while another version did not include the warning.
Predictably, participants who had the opportunity to purchase the cigarettes soon after seeing the ad bought less if the ad they saw included the warning.
In contrast, participants who were given the opportunity to purchase the cigarettes a few days later bought more if the ad included the warning. The same outcome emerged when the researchers ran a similar experiment with ads for artificial sweeteners.
According to Carmon and his colleagues, the warnings backfired because the psychological distance created by the delay between exposure to the ad and the customer decision made the side effects seem abstract—participants came to see the warning as an indication of the firm's honesty and trustworthiness.
In fact, participants evaluated drugs for erectile dysfunction and hair loss that had potentially serious side effects more favorably, and as more trustworthy, when they were told the products weren't on the shelves yet.
While conventional wisdom suggests that explicit warnings about dangerous side effect will make people think twice before taking medical risks, these findings suggests otherwise. The researchers believe that their findings are important because these kinds of warnings are so ubiquitous, accompanying many different products or services beyond medications, including medical procedures, financial investments, and sporting activities.
Given how frequently we are exposed to such warnings, Carmon hopes to bring greater attention to their potential to backfire. "This effect may fly under the radar since people who try to protect the public - regulatory agencies, for example - tend to test the impact of a warning shortly after consumers are exposed to it," says Carmon. "By doing so, they miss out on this worrisome delayed outcome."
|
|
|
|
Post by GodFather on Sept 26, 2013 22:11:58 GMT 5.5
Researchers use nanoparticles to deliver vaccines to lungs
Many viruses and bacteria infect humans through mucosal surfaces, such as those in the lungs, gastrointestinal tract and reproductive tract. To help fight these pathogens, scientists are working on vaccines that can establish a front line of defense at mucosal surfaces. Vaccines can be delivered to the lungs via an aerosol spray, but the lungs often clear away the vaccine before it can provoke an immune response. To overcome that, MIT engineers have developed a new type of nanoparticle that protects the vaccine long enough to generate a strong immune response - not only in the lungs, but also in mucosal surfaces far from the vaccination site, such as the gastrointestinal and reproductive tracts.
Such vaccines could help protect against influenza and other respiratory viruses, or prevent sexually transmitted diseases such as HIV, herpes simplex virus and human papilloma virus, says Darrell Irvine, an MIT professor of materials science and engineering and biological engineering and the leader of the research team. He is also exploring use of the particles to deliver cancer vaccines.
"This is a good example of a project where the same technology can be applied in cancer and in infectious disease. It's a platform technology to deliver a vaccine of interest," says Irvine, who is a member of MIT's Koch Institute for Integrative Cancer Research and the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University.
Irvine and colleagues describe the nanoparticle vaccine in the Sept. 25 issue of Science Translational Medicine. Lead authors of the paper are recent PhD recipient Adrienne Li and former MIT postdoc James Moon.
Only a handful of mucosal vaccines have been approved for human use; the best-known example is the Sabin polio vaccine, which is given orally and absorbed in the digestive tract. There is also a flu vaccine delivered by nasal spray, and mucosal vaccines against cholera, rotavirus and typhoid fever.
To create better ways of delivering such vaccines, Irvine and his colleagues built upon a nanoparticle they developed two years ago. The protein fragments that make up the vaccine are encased in a sphere made of several layers of lipids that are chemically "stapled" to one another, making the particles more durable inside the body.
"It's like going from a soap bubble to a rubber tire. You have something that's chemically much more resistant to disassembly," Irvine says.
This allows the particles to resist disintegration once they reach the lungs. With this sturdier packaging, the protein vaccine remains in the lungs long enough for immune cells lining the surface of the lungs to grab them and deliver them to T cells. Activating T cells is a critical step for the immune system to form a memory of the vaccine particles so it will be primed to respond again during an infection.
In studies of mice, the researchers found that HIV or cancer antigens encapsulated in nanoparticles were taken up by immune cells much more successfully than vaccine delivered to the lungs or under the skin without being trapped in nanoparticles.
HIV does not infect mice, so to test the immune response generated by the vaccines, the researchers infected the mice with a version of the vaccinia virus that was engineered to produce the HIV protein delivered by the vaccine.
Mice vaccinated with nanoparticles were able to quickly contain the virus and prevent it from escaping the lungs. Vaccinia virus usually spreads to the ovaries soon after infection, but the researchers found that the vaccinia virus in the ovaries of mice vaccinated with nanoparticles was undetectable, while substantial viral concentrations were found in mice that received other forms of the vaccine.
Mice that received the nanoparticle vaccine lost a small amount of weight after infection but then fully recovered, whereas the viral challenge was 100 percent lethal to mice who received the non-nanoparticle vaccine.
"Giving the vaccine at the mucosal surface in the nanocapsule form allowed us to completely block that systemic infection," Irvine says.
The researchers also found a strong memory T cell presence at distant mucosal surfaces, including in the digestive and reproductive tracts. "An important caveat is that although immunity at distant mucus membranes following vaccination at one mucosal surface has been seen in humans as well, it's still being worked out whether the patterns seen in mice are fully reproduced in humans," Irvine says. "It might be that it's a different mucosal surface that gets stimulated from the lungs or from oral delivery in humans."
The particles also hold promise for delivering cancer vaccines, which stimulate the body's own immune system to destroy tumors.
To test this, the researchers first implanted the mice with melanoma tumors that were engineered to express ovalbumin, a protein found in egg whites. Three days later, they vaccinated the mice with ovalbumin. They found that mice given the nanoparticle form of the vaccine completely rejected the tumors, while mice given the uncoated vaccine did not.
Further studies need to be done with more challenging tumor models, Irvine says. In the future, tests with vaccines targeted to proteins expressed by cancer cells would be necessary.
The research was funded by the National Cancer Institute, the Ragon Institute, the Bill and Melinda Gates Foundation, the U.S. Department of Defense and the National Institutes of Health.
The nanoparticle technology has been patented and licensed to a company called Vedantra, which is now developing infectious-disease and cancer vaccines.
|
|
|
|
Post by GodFather on Sept 26, 2013 22:13:17 GMT 5.5
Amgen and ShanghaiTech University announce plans for Amgen China R&D center
Amgen (NASDAQ: AMGN) and ShanghaiTech University today announced the two organizations have entered into a memorandum of understanding (MOU) to form a strategic partnership for the advancement of biopharmaceutical discovery and translational research in China. This agreement includes plans for Amgen to open a China research and development (R&D) center at ShanghaiTech University.
"Amgen and ShanghaiTech University share mutual goals of scientific excellence and rigor and will benefit from each other's strength and expertise in advancing biopharmaceutical discovery in China," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Expansion into China is a business priority for Amgen and opening this R&D center is another clear and important step forward in Amgen's commitment to the China market."
Under the terms of the MOU, Amgen will co-locate its China R&D center with ShanghaiTech University's two life science institutes: the Shanghai Institute for Advanced Immunochemical Studies (SIAIS) and the iHuman Institute.
"We are pleased to be partnering with Amgen," said Professor Mianheng Jiang, chairman of Executive Committee of ShanghaiTech University. "ShanghaiTech aims to build a research-oriented university that provides a dynamic approach to learning and ultimately solving problems facing society. This partnership is a commitment to develop more effective bio-medicine for the benefits of the patients in China and in the whole world."
"We are excited about this unique opportunity to work with ShanghaiTech University," added Mingqiang Zhang, Ph.D., vice president of China Research and Development at Amgen. "The combination of Amgen's industry-leading expertise in biopharmaceuticals and the world-class academic excellence of scientists at the SIAIS and iHuman institutes of ShanghaiTech will be a very powerful force in advancing drug discovery and development. We aim to address unmet medical needs that are particularly relevant for patients in China."
"We are delighted that Amgen, a key player in the global biologics sector, will be co-locating its China R&D center at ShanghaiTech University," said Professor Richard A. Lerner, founding director of Shanghai Institute for Advanced Immunochemical Studies, an antibody research institute of ShanghaiTech University. "We aim to become one of the world's leading antibody research institutes and the co-location of Amgen's China R&D center with us will help to steer our research to be more applicable and to ultimately help patients in the fight against serious illnesses."
Amgen expects its China R&D center will be fully operational in 2014.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
About ShanghaiTech University
ShanghaiTech University is a research university in the making. Recently endorsed by China's Ministry of Education, it is jointly sponsored and organized by the Shanghai Municipal Government and the Chinese Academy of Sciences (CAS), with the former being responsible for operation.
About SIAIS
Founded by ShanghaiTech University on October 12th, 2012, the Shanghai Institute for Advanced Immunochemical Studies (SIAIS) aims to become a first-class, leading antibody research institute in the world. It focuses on elucidating the most fundamental problems in life science research, particularly in immunochemistry. Its international governing board is comprised of world recognized scientists, including pioneering antibody researchers and Nobel Prize winners in Chemistry.
About iHuman Institute
The iHuman Institute is a new international effort established as a research institute located on the campus of ShanghaiTech University. What makes the iHuman Institute special is that it is focused exclusively on the basic and applied science of human cell signaling, integrating multiple tools for scientific discovery, and bringing together leading researchers throughout the world. Cell surface receptors and their related intracellular proteins are responsible for human cellular communications with each other and their environment, and are involved in a wide range of physiological activities. Such a central role in human biology makes cell signaling the target for intervention for tuning physiological responses and fighting numerous conditions and diseases. These proteins are central to understanding the evolution of mankind and human cognition at a molecular level.
|
|
|
|
Post by GodFather on Sept 27, 2013 15:30:00 GMT 5.5
Study finds steroids may persist longer in the environment than expected
Assessing the risk posed to aquatic organisms by the discharge of certain steroids and pharmaceutical products into waterways is often based on a belief that as the compounds degrade, the ecological risks naturally decline. But there's growing sentiment that once in the environment, some of these bioactive organic compounds may transform in a way that makes their presumed impact less certain.
A new study led by the University of Iowa and published online Thursday in the journal Science found this was the case with the anabolic steroid trenbolone acetate and two other drugs.
Once popular in the bodybuilding and weightlifting communities, trenbolone acetate is now banned for human use. However, it is federally approved for use by the beef industry to promote weight gain and increase feeding efficiency in cattle.
In lab tests followed by field experiments, the researchers found that trenbolone does not fully break down in water as believed, retaining enough of a chemical residue to regenerate itself in the environment under certain conditions, to an extent that the drugs' lives may be prolonged, even in trace amounts.
Researchers says the study is a first step toward better understanding the environmental role and impact of steroids and pharmaceutical products, all of which have been approved by the federal government for various uses and that have been shown to improve food availability, environmental sustainability and human health.
"We're finding a chemical that is broadly utilized, to behave in a way that is different from all our existing regulatory and risk-assessment paradigms," says David Cwiertny, assistant professor in engineering at the University of Iowa and a co-corresponding author on the paper."What our work hopefully will do is help us better understand and assess the environmental fate of emerging contaminant classes. There are a variety of bioactive pharmaceuticals and personal-care products that we know are present in trace amounts in our water supply. We should use what we're learning about trenbolone to more closely scrutinize the fate and better mitigate the impact of these products in the environment."
The team found similar results for dienogest, a hormone used in a birth-control pill called Natazia, and dienedone, a banned anabolic steroid that has been marketed as a body-building supplement.
Trenbolone acetate is implanted in the ears of more than 20 million cattle in the United States, according to studies cited by the researchers in their paper.
The drug is metabolized and then excreted by livestock, and makes its way into waterways mainly through runoff.
The steroid has been considered safe due to its rapid degradation, with studies pointing to an environmental half-life of less than a day. But there has been concern that it and other synthetic drugs, when found in concentrated amounts, can be harmful to aquatic species and the environment generally. Studies have pointed to steroids and other drugs' effects on fish, through fewer eggs produced by females to skewing the sex of some species.
"We rarely see fish kills anymore, and we probably aren't discharging many carcinogens into surface waters anymore. But I don't believe this necessarily means that our water is safe for aquatic organisms," says Edward Kolodziej, associate professor in engineering at the University of Nevada-Reno and the other corresponding author on the Science paper. "It just might be harder to characterize the adverse effects associated with contaminant exposures these days."
Sunlight is one catalyst for breaking down compounds in the environment. But in this study, by simulating day and night in the lab, the research team found that the steroid's chemical compounds never fully disappeared in daylight. Moreover, during a simulated night, under typical surface water conditions, some of the compounds regenerated themselves, to as much as 60 percent of the metabolite's initial mass, when tracked over a 120-hour period.
"We knew something unique was going on," Cwiertny says. "In daylight, it essentially hides in another form, to evade analysis and detection, and then at nighttime it readily grows back."
More of the drug's mass was regenerated - up to 88 percent in one highly acidic state (pH 2) - when water temperature was higher and when it was more acidic or alkaline, the team found.
The researchers validated the lab results with two experiments in the field - one with water culled from the Iowa River in Iowa City, Iowa and the other from samples taken from a collection pond at a cattle rangeland and research operation run by the University of California.
Shen Qu, a post-doctoral researcher at the UI who studied under Cwiertny, is the first author on the paper. Contributing authors from the UI include Sarah Long, graduate research assistant in chemistry; James Gloer, chemistry professor; and Matthew Tarnoff, a senior in engineering. Jonas Baltrusaitis, who earned his doctorate at the UI and is now at the University of Twente, in the Netherlands, is a contributing author. Other contributing authors, all from Nevada-Reno, include Gerrad Jones, Peter Benchetler, Emily Cole and Kaitlin Kimbrough. Eric Patterson, now at Stony Brook University but who worked on the study while at Truman State University, also contributed to the paper.
The U.S. Department of Agriculture (grant numbers: 2010-65102-20425 and 2010-65102-20407), National Institutes of Health (grant numbers: S10-RR025500, UL 1RR024979 and P20 GM103440-11) and the National Science Foundation (grant numbers: CHE-074096, CHE-1039925 and CHE-1044356).
|
|
|
|
Post by GodFather on Sept 27, 2013 15:38:32 GMT 5.5
Bayer's investigational drug Riociguat granted FDA orphan drug designation
Bayer HealthCare today announced that the U.S. Food and Drug Administration’s (FDA) Office of Orphan Products Development has granted two separate orphan drug designations for its investigational, oral medication riociguat for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders.
Bayer submitted a New Drug Application (NDA) for riociguat in February 2013 for two indications: (i) the treatment of PAH (WHO Group 1) to improve exercise capacity, improve WHO functional class and delay clinical worsening; and (ii) the treatment of persistent/recurrent CTEPH (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
Riociguat has been approved under the trade name Adempas® by Health Canada for the treatment of inoperable, or persistent /recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after surgery in adult patients with WHO Functional Class II or III pulmonary hypertension in September.
PAH and CTEPH are both life-threatening forms of pulmonary hypertension that cause significantly increased pressure in the pulmonary arteries. Riociguat is an investigational, oral medication for the treatment of adult patients with PAH or persistent/recurrent CTEPH after surgical treatment or inoperable CTEPH. If approved by the FDA, it would create a new class of drugs available in the U.S. Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide (NO) and insufficient stimulation of soluble guanylate cyclase (sGC). Riociguat stimulates sGC independent of NO and increases the sensitivity of sGC to NO.
About Pulmonary Arterial Hypertension (PAH)
PAH, one of the five types of pulmonary hypertension (PH), is a progressive and life-threatening disease in which the blood pressure in the pulmonary arteries is significantly increased due to vasoconstriction and which can lead to heart failure and death. PAH is characterized by morphological changes to the endothelium of the artery of the lungs causing remodeling of the tissue, vasoconstriction and thrombosis-in-situ. As a result of these changes, the blood vessels in the lungs are narrowed, making it difficult for the heart to pump blood through to the lungs. PAH is a rare disease and affects an estimated 52 people per million globally. It is more prevalent in younger women than men. In most cases, PAH has no known cause and, in some cases, it can be inherited.
Despite the availability and advantages of several approved PAH therapies, the prognosis of patients remains poor and new treatment options are needed. Mortality of PAH patients remains high and is still 15% at 1 year; 32% at 3 years after diagnosis.
About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
CTEPH is a progressive and life-threatening disease and a type of PH, in which it is believed that thromboembolic occlusion (organized blood clots) of pulmonary vessels gradually lead to an increased blood pressure in the pulmonary arteries, resulting in an overload of the right heart. CTEPH is a rare disease and is comparable in terms of population size to PAH, though there are fewer diagnoses made so far. CTEPH may evolve after prior episodes of acute pulmonary embolism, but the pathogenesis is not yet completely understood. The standard and potentially curative treatment for CTEPH is pulmonary endarterectomy (PEA), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar material. However, a considerable number of patients with CTEPH (20%-40%) are not operable and in up to 35% of patients, the disease persists or reoccurs after PEA. To date, no approved pharmacological therapy exists for CTEPH and, as a result, there is an urgent unmet medical need for patients who are unable to undergo surgery or who have persistent or recurrent pulmonary hypertension (PH) after surgery.
About Riociguat
Riociguat (BAY 63-2521) is a soluble guanylate cyclase (sGC) stimulator, the first member of a novel class of compounds, discovered and developed by Bayer as an oral treatment to target a key molecular mechanism underlying PH. Riociguat is being investigated as a new and specific approach to treat different types of PH. sGC is an enzyme found in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme enhances synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). cGMP plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.
PH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of sGC. Riociguat has a unique mode of action - it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat, as a stimulator of sGC, addresses NO deficiency by restoring the NO-sGC-cGMP pathway, leading to increased generation of cGMP.
With its novel mode of action, Riociguat has the potential to overcome a number of limitations of currently approved PAH therapies, including NO dependence, and is the first drug which has shown clinical benefits in CTEPH, where no pharmacological treatment is approved.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.6 billion (2012), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 54,900 employees (Dec 31, 2012) and is represented in more than 100 countries.
|
|
|
|
Post by GodFather on Oct 1, 2013 16:07:52 GMT 5.5
Olivier Brandicourt appointed as new CEO of Bayer HealthCare
Olivier Brandicourt (57) has been appointed Chairman of the Board of Management of Bayer HealthCare and member of the Bayer AG Executive Council effective November 1, 2013. Since March 2013, Professor Wolfgang Plischke has led Bayer HealthCare on an interim basis in addition to his existing duties as a Bayer AG Board Member.
"With Olivier Brandicourt we have found a strong leader with outstanding international experience and a successful track record in the healthcare industry. I am convinced that he can significantly contribute to the further growth of our healthcare business," said Bayer Group CEO Dr. Marijn Dekkers.
Brandicourt has 25 years of international experience in the pharmaceutical industry, including executive responsibilities in France, the United States, Canada and the United Kingdom. He has been a member of the Executive Leadership Team of Pfizer Inc., New York, USA, for the last three years. Until recently he was President and General Manager of the Emerging Markets and Established Products Business Units. Before that he held senior operational positions as President of the Global Specialty Business Unit, and until 2012 he was head of the Global Primary Care Business Unit. Furthermore, he previously held senior regional and country management positions at Pfizer and positions across a range of disciplines including medical and marketing at Warner-Lambert/Parke-Davis.
"I am looking forward to joining the Bayer team. With a clear focus on research and development as well as a passion and dedication to improving people’s lives, Bayer has an excellent track record in bringing innovation to the market," said Olivier Brandicourt.
Olivier Brandicourt holds a medical degree with a subspecialty in infectious diseases and tropical medicine, as well as a master’s degree in biology from Paris 12 University, France. After completing his studies, Brandicourt spent two years in the Republic of Congo as a doctor and eight years with the Institute for Infectious and Tropical Diseases at Pitié-Salpêtrière Hospital in Paris, spending half this time in West and Central Africa working on malaria research. Brandicourt is an Honorary Fellow of the Royal College of Physicians in London, UK, and a member of the Children’s Aid Society's Board of Trustees in New York. He is married with three grown-up children.
Bayer: Science For A Better Life
Bayer is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. As an innovation company, it sets trends in research-intensive areas. Bayer's products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2012, the Group employed 110,000 people and had sales of €39.7 billion. Capital expenditures amounted to €1.9 billion, R&D expenses to €3.0 billion.
|
|
|
|
Post by GodFather on Oct 1, 2013 16:13:05 GMT 5.5
Nintedanib* extended survival beyond one year for advanced adenocarcinoma patients after prior first-line chemotherapy
New analysis of data from the LUME-Lung 1 Phase III clinical trial showed that the novel investigational compound nintedanib*, an oral triple angiokinase inhibitor that targets three receptors crucially involved in angiogenesis and tumour growth, provided a significant and clinically relevant overall survival benefit for advanced non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology.(1) The results were presented at the European Cancer Congress in Amsterdam.
"Adenocarcinoma is the most common form of non-small cell lung cancer and as the majority of patients with an advanced stage of the disease will ultimately progress after initial therapy, effective second-line treatments are vital," said Dr. Anders Mellemgaard, Department of Oncology, Herlev University Hospital, Copenhagen. "Recent treatment advances for this sizeable patient population have been limited, but we have reached an important milestone with nintedanib. LUME-Lung 1 showed that nintedanib, when added to chemotherapy, was effective in extending overall survival by 2.3 months for advanced non-small cell lung cancer patients with adenocarcinoma histology and could become an important second-line option for these patients."
LUME-Lung 1 showed nintedanib* plus docetaxel provided a statistically significant increase in median overall survival from 10.3 months in the placebo arm to 12.6 months in the nintedanib* arm (HR: 0.83, p-value: 0.04).1 In addition, the data demonstrated that the earlier adenocarcinoma patients failed first line chemotherapy, the bigger the benefit that nintedanib* provided.1 Compared to the overall adenocarcinoma patient population, patients with advanced adenocarcinoma who progressed within 9 months after start of their first-line treatment (T<9months) achieved a larger median overall survival benefit of 3 months (10.9 with nintedanib* plus docetaxel vs. 7.9 months with placebo plus docetaxel).(1)
The analysis of the overall survival benefit observed in adenocarcinoma T<9 months patients suggests T<9months to be a predictive clinical biomarker of nintedanib* benefit in second-line, advanced NSCLC patients with adenocarcinoma histology.(1,2)
The most common adverse events (AEs) in LUME-Lung 1 were gastrointestinal side effects and reversible liver enzyme elevations which were manageable by supportive treatment or dose reduction (adverse events placebo vs. nintedanib*: nausea 18% vs. 24%, vomiting 9% vs. 17%, diarrhoea 22% vs. 42% and liver enzyme elevation 8% vs. 29%). Withdrawal due to adverse events was similar in both arms, as were Grade 3, bleeding or thromboembolic events.1 The trial results demonstrated that despite the observed adverse events, patients benefited from the additional efficacy of nintedanib*, when added to docetaxel, without significantly further impacting their quality of life.
Boehringer Ingelheim endeavours to make nintedanib* available to patients around the world. Submissions worldwide are currently under preparation.
About the LUME-Lung 1 trial
LUME-Lung 1 was a randomised, double-blind, Phase III study comparing nintedanib* plus docetaxel in patients with locally advanced/metastatic NSCLC after first-line therapy, with placebo plus docetaxel. The study included 1,314 patients, in Europe, Asia and South Africa, randomised to receive nintedanib* 200 mg twice daily plus docetaxel 75mg/m2 once a day, for 3 weeks (n=655) or placebo plus docetaxel (n=659).
LUME-Lung 1 is part of the wider Boehringer Ingelheim LUME-Lung Phase III programme for nintedanib*, investigating the safety and efficacy of nintedanib* in NSCLC patients after first line chemotherapy treatment. 1,773 patients were enrolled, making this one of the largest Phase III study programmes in this NSCLC patient population to date.
About Nintedanib*
Nintedanib* is an oral triple angiokinase inhibitor that targets three growth factor receptors simultaneously: vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR alpha and beta), and fibroblast growth factor receptors (FGFR 1-3).(3) All three receptors are crucially involved in the formation and maintenance of new blood vessels (angiogenesis); their blockade may lead to the inhibition of angiogenesis, which plays a critical role in tumour growth and spread.(4,5)
Nintedanib* is currently being investigated in patients with various solid tumours including advanced NSCLC, ovarian cancer, liver cancer (hepatic cell carcinoma), kidney cancer (renal cell carcinoma), and colorectal cancer.
About Lung Cancer
Lung cancer is one of the most common and most deadly forms of cancer in the world, it accounts for 1.6 million new cancer cases annually.(6) Because of its poor prognosis, 1.38 million deaths each year are attributable to lung cancer.6 Overall, lung cancer is the cause of 18% of all cancer deaths.(6) Approximately 228,190 (13%) of all new cases of cancer are lung cancers(7) nd smoking is attributed as the main cause.
About Boehringer Ingelheim in Oncology
Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research programme to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world's leading cancer centres, Boehringer Ingelheim's commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumours and haematological cancers.
The current focus of research includes compounds in three areas: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition. In the EU, Taiwan and Mexico, afatinib is approved under the brand name GIOTRIF®, and in the U.S. under the brand name GILOTRIFTM for use in patients with distinct types of NSCLC. Afatinib is under regulatory review by health authorities in Asia and other countries. Nintedanib*, an angiogenesis inhibitor is currently in Phase III clinical development in NSCLC and ovarian cancer. In the area of cell-cycle kinase inhibition, volasertib* is in Phase III development for acute myeloid leukaemia.
Boehringer Ingelheim's oncology pipeline is evolving and demonstrates the company's continued commitment to advance the disease area.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.
In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.
*Nintedanib and volasertib are investigational compounds and are not yet approved. Their safety and efficacy has not yet been fully established.
1. Mellemgaard A, Kaiser R, Douillard J-Y et al. Analysis of overall survival in adenocarcinoma NSCLC patients receiving 2nd line combination treatment with nintedanib (BIBF-1120) + docetaxel in the LUME-Lung 1 trial: a randomised, double-blind, placebo-controlled phase 3 study. Oral presentation on 29 September 2013 at 09.00 at The European Cancer Congress 2013 Abstract. no 3409.
2. Kaiser R, Barrueco J, Reck M et al. Identification of a clinical biomarker for 2nd line combination with nintedanib in adenocarcinoma non-small cell lung cancer (NSCLC) patients in two phase III trials. Poster presentation on 29 September 2013 at 14.00 at The European Cancer Congress 2013. Abstract no. 3479.
3. Hilberg F, Roth GJ, Krssak M, et al. BIBF1120: triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Res 2008;68: 4774-82.
4. Folkman N. Clinical applications of research on angiogenesis. N Engl J Med 1995;333: 1757-63.
5. Bousquet C, Lamande N, Brand M, et al. Suppression of angiogenesis, tumor growth, and metastasis by adenovirus-mediated gene transfer of human angiotensinogen. Mol Ther 2006;14:175-82.
6. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
7. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Bethesda, MD, seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, 2013.
|
|
|
|
Post by GodFather on Oct 1, 2013 16:16:06 GMT 5.5
Cimzia® (certolizumab pegol) approved by the U.S. FDA for treatment of adult patients with active psoriatic arthritis
UCB announced today that the U.S. Food and Drug Administration (FDA) has approved Cimzia® (certolizumab pegol) for the treatment of adult patients with active psoriatic arthritis (PsA). PsA is a chronic, inflammatory condition that causes pain, swelling and stiffness in and around the joints and tendons, and usually occurs in combination with psoriasis.(1,2)
"The FDA's approval of Cimzia® for the treatment of active PsA provides an additional, effective treatment option for those living with the condition. Psoriatic arthritis brings with it a heavy disease burden that often strikes during the prime years of life, impacting health-related quality of life and physical function," said Dr. Philip J. Mease, Director Rheumatology Research, Swedish Medical Center and Clinical Professor, University of Washington School of Medicine, Seattle, WA, U.S.
"UCB has a long heritage in rheumatology, with many years of clinical experience with Cimzia® in moderate-to-severe rheumatoid arthritis. This approval represents the third indication for Cimzia® in the U.S. and reaffirms the value of our commitment to developing medicines that treat serious, chronic diseases, and in turn help those with PsA," said Professor Dr. Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President, UCB.
In most people with PsA, psoriasis develops before joint problems.(1) When hands and feet are affected in PsA, nail changes can occur, as well as swelling in the fingers and toes (dactylitis).(1) PsA affects approximately 0.24 percent of the population worldwide1; up to 30 percent of the estimated 7.5 million psoriasis patients in the U.S. will develop PsA.(3,4) Research suggests that nearly one in four people with psoriasis in the U.S. may have undiagnosed PsA.(2)
FDA approval of Cimzia® for active PsA is based on data from the RAPIDTM-PsA study, an ongoing, Phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of certolizumab pegol in 409 patients with active and progressive adult onset PsA. Patients received a loading dose of Cimzia® 400 mg at Weeks 0, 2 and 4 or placebo, followed by either Cimzia® 200 mg every other week, Cimzia® 400 mg every 4 weeks, or placebo every other week. Patients were evaluated for signs and symptoms of PsA using the ACR20 response at week 12 and for structural damage using the modified Total Sharp Score (mTSS) at Week 24.(5)
ACR20, 50, and 70 response rates at weeks 12 and 24 were higher for each Cimzia® dose group relative to placebo. Patients treated with Cimzia® 200 mg every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at Week 24, as measured by change from baseline in total modified mTSS Score. Patients treated with Cimzia® 400 mg every four weeks did not demonstrate greater inhibition of radiographic progression at Week 24, compared with placebo-treated patients. Treatment with Cimzia® also resulted in improvement in skin manifestations in patients with PsA. However, the safety and efficacy of Cimzia® in the treatment of patients with plaque psoriasis has not been established.(6)
Adverse events occurred in 62% of patients in the certolizumab pegol group (combined dose) compared to. 68% of patients in the placebo group. Serious adverse events occurred in 7% of patients in the certolizumab pegol group (combined dose) compared to 4% of patients in the. placebo group.(7) The safety profile for patients with PsA treated with Cimzia® was similar to the safety profile seen in patients with RA and in patients with previous experience with Cimzia®.6 Please see important safety information at the end of this press release for additional details about adverse events associated with Cimzia®.
In the U.S., Cimzia® is also approved for the treatment of adults with moderately to severely active rheumatoid arthritis. In addition, it is approved for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.(7) The FDA is also reviewing a filing for Cimzia® in the treatment of adults with active axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS).
In the EU, Cimzia® in combination with methotrexate (MTX) is approved for the treatment of moderate to severe active rheumatoid arthritis in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.(8)
The European Medicines Agency is currently reviewing a filing for certolizumab pegol in the treatment of adult patients with active PsA. In September 2013, the European Medicines Agency'
About UCB
UCB, Brussels, Belgium is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With 9000 people in approximately 40 countries, the company generated revenue of EUR 3.4 billion in 2012. UCB is listed on Euronext Brussels (symbol: UCB).
1. Psoriatic Arthritis, Genetics Home Reference. Accessed September 2013 from ghr.nlm.nih.gov/condition/psoriatic-arthritis
2. National Psoriasis Foundation. [Facts about Psoriasis and Psoriatic Arthritis] Accessed September 2013 from www.psoriasis.org/document.doc?id=191
3. About Psoriasis. National Psoriasis Foundation. Accessed September 2013 from www.psoriasis.org/about-psoriasis
4. Psoriatic Arthritis. National Psoriasis Foundation. Accessed September 2013 from www.psoriasis.org/psoriatic-arthritis
5. Mease, P., Fleischmann, R. M. et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomized placebo-controlled study (RAPID-PsA) Ann Rheum Dis 2013;0:1–8. doi:10.1136/annrheumdis-2013-203696. Accessed September 2013 from ard.bmj.com/content/early/2013/08/28/annrheumdis-2013-203696.full.pdf
6. Cimzia® US Prescribing Information. Accessed September 2013 from www.ucb.com/_up/ucb_com_products/documents/Cimzia_COL_11_2012.pdf
7. Mease, P., Fleischmann, R. M. et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis with and without prior anti-TNF exposure: 24 week results of a phase 3 double-blind randomized placebo-controlled study. Arthritis Rheum. 2012;64(Suppl 10);S1107. ACR Meeting & 47th Annual meeting of the Association of Rheumatology Health Professionals (ARHP); Washington; D.C., USA
8. Cimzia® EU Summary of Product Characteristics. Accessed September 2013 from www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf
|
|
