September 9, 2009 (VIVUS) - VIVUS, Inc. (Nasdaq: VVUS) today announced positive results from two final, phase 3 pivotal 56-week studies, EQUIP (OB-302) and CONQUER (OB-303), evaluating the safety and efficacy of Qnexa(TM), an investigational drug, in more than 3,750 patients across 93 sites. The EQUIP and CONQUER studies met all primary endpoints by demonstrating statistically significant weight loss with all three doses of Qnexa, as compared to placebo. Patients taking Qnexa also achieved significant improvements in cardiovascular and metabolic risk factors including blood pressure, lipid levels, and type 2 diabetes.The outstanding results from the EQUIP and CONQUER studies, in addition to the results from EQUATE that were reported late last year, confirm the positive effect of Qnexa and underscore the important role this therapy may play in the lives of patients battling obesity and related co-morbidities, if approved by the FDA," stated Leland Wilson, president and chief executive officer of VIVUS. "The results of the phase 3 program, designed and executed after Special Protocol Assessments were completed by the FDA, exceed the FDA benchmarks for clinically significant weight loss. The results support the company's plan to file a New Drug Application with the FDA by the end of 2009 and submit the results from the studies for publication in peer-reviewed journals. We believe these results may provide a compelling opportunity for global pharmaceutical companies, and we intend to initiate partnering discussions now that we have the full data set in hand."

Wilson added, "We are proud of the results of our Qnexa phase 3 program, and I would like to thank Dr. Thomas Najarian, the inventor of Qnexa, the entire development team at VIVUS, Dr. David Orloff and his staff at Medpace, the clinical research organization that managed these studies, and the clinical investigators and patients who participated in the Qnexa clinical trials."

Qnexa is a proprietary formulation and unique dosing regimen that combines two well known pharmaceutical therapies - phentermine and topiramate - to create a novel, patented therapy. The phase 3 program evaluated three doses of Qnexa (numbers reflect milligrams of phentermine and controlled release topiramate, respectively):

-- Qnexa 15/92 (full dose)
-- Qnexa 7.5/46 (mid dose)

-- Qnexa 3.75/23 (low dose)

"The weight loss observed with Qnexa in these two one-year, double-blind, randomized trials far exceeds the weight loss observed for other agents reported in literature," said Kishore Gadde, MD, director of obesity clinical trials at Duke University and a lead investigator. "The efficacy and safety results confirm the earlier findings of our phase 2 study, which showed a very good efficacy and benefit/risk profile. Importantly, the medical benefits of this treatment in reducing the risk of weight-related co-morbidities such as hypertension, diabetes, and dyslipidemia could establish Qnexa as a major advancement in the management of obesity."

EQUIP (OB-302) Results

The EQUIP study included 1,267 morbidly obese patients (1,050 females and 217 males) across 93 centers in the United States. The average baseline BMI of the study population was 42.1 kg/m(2) and baseline weight was 256 pounds. Patients had a 4-week dose titration period followed by 52 weeks of treatment. The study was a randomized, double-blind, placebo-controlled, 3-arm, prospective trial with patients randomized to receive once-a-day treatment with low-dose Qnexa, full-dose Qnexa or placebo. Patients were asked to follow a hypocaloric diet representing a 500-calorie/day deficit and advised to implement a simple lifestyle modification program. Results from the study are as follows:

-- Average weight loss for Qnexa patients completing the EQUIP study was 37
pounds and 18 pounds with full-dose Qnexa and low-dose Qnexa,
respectively, as compared to 6 pounds in the placebo group;
-- 60% of the full-dose Qnexa patients who completed the study lost at
least 10% of their baseline weight;
-- 43% of the full-dose Qnexa patients who completed the study lost at
least 15% of their baseline weight;
-- Completion rate for EQUIP was 47%, 57%, 59% for patients taking placebo,
low-dose Qnexa and full-dose Qnexa, respectively; and

-- Patients treated with full-dose Qnexa had significant improvements in
blood pressure, triglycerides and cholesterol.

CONQUER (OB-303) Results

The CONQUER study included 2,487 overweight and obese patients (1,737 females and 750 males) with high blood pressure, high cholesterol or type 2 diabetes across 93 centers in the United States. The average baseline BMI of the study population was 36.6 kg/ m2 and baseline weight was 227 pounds. Patients had a 4-week dose titration period followed by 52 weeks of treatment. The study was a randomized, double-blind, placebo-controlled, 3-arm, prospective trial with patients randomized to receive once-a-day treatment with mid-dose Qnexa, full-dose Qnexa or placebo. Patients were asked to follow a hypocaloric diet representing a 500-calorie/day deficit and advised to implement a simple lifestyle modification program. Results from the study are as follows:

-- Average weight loss for Qnexa patients who completed the CONQUER study
was 30 pounds and 24 pounds with full-dose Qnexa and mid-dose Qnexa,
respectively, as compared to 6 pounds in the placebo group.
-- In the CONQUER study subset analysis, higher risk patients, defined as
those in the upper 25th percentile of a specific co-morbidity, who were
treated with full-dose Qnexa for 56 weeks achieved the following changes
in cardiovascular risk factors:
-- Reduction in systolic blood pressure of 20 mmHg from 147 mmHg at
baseline, as compared to a reduction of 14 mmHg in the placebo group
(p<0.0001). This improvement occurred in the presence of a
significant reduction in blood pressure medications in Qnexa-treated
patients as compared to placebo;
-- Reduction in triglyceride levels of 98 mg/dL from 268 mg/dL at
baseline, as compared to a decrease of 42 mg/dL from 262 mg/dL at
baseline in the placebo group (p<0.0001);
-- Reduction in hemoglobin A1c levels of 0.6% from 7.3% at baseline as
compared to a reduction of 0.1% from 7.4% at baseline for the
placebo patients (p<0.0001). These improvements occurred in the
presence of a significant reduction in antidiabetic medications in
Qnexa-treated patients compared with placebo. All patients were
treated to standard of care for type 2 diabetes. 64% of the
full-dose Qnexa patients who completed the study lost at least 10%
of their baseline weight;
-- 39% of the full-dose Qnexa patients who completed the study lost at
least 15% of their baseline weight; and

-- Completion rates for CONQUER were 57%, 69%, 64% for patients taking
placebo, mid-dose Qnexa, and full-dose Qnexa, respectively.

Across both 56-week studies comprised of more than 3,750 patients, the most commonly reported side effects were dry mouth, tingling, constipation, altered taste and insomnia. Monthly assessments using prospective psychometric instruments in accordance with FDA's guidance showed no signal for suicidality risk. There were no suicide attempts or suicidal behaviors, and there was no signal for suicidal ideation across all treatment groups including placebo. Depression or depressed mood adverse events of a moderate to severe nature were less than 2% and were similar among patients in the Qnexa and placebo groups. Overall, depression scores, quality of life including self esteem and general health significantly improved for patients on Qnexa.

"I have seen dramatic and sustained weight loss with Qnexa as well as notable improvements in cardiovascular risk factors, diabetes, emotional well being and quality of life in my patients," commented Michelle Look, M.D., FAAFP, of the San Diego Sports Medicine and Family Health Center and a lead investigator in the studies. "What is so striking for me is how many of my patients were able to achieve weight loss with Qnexa for the first time after many years of battling weight problems without success. The excellent tolerability of Qnexa allowed patients to stay on therapy for a year, as evidenced by the strong completer rates."

Other Safety Studies

VIVUS completed a thorough QT prolongation (TQT) study evaluating subjects taking Qnexa. The study was completed with no signal for QT prolongation. Subjects taking Qnexa also underwent complex and extensive cognitive and psychomotor testing using validated, FDA accepted testing methodologies. There was no clinically significant change in overall cognitive function or effect on psychomotor skills seen in patients taking Qnexa.

"These data are significant, and when coupled with my own experience treating patients with Qnexa, clearly demonstrate that it is one of the promising pharmaceutical therapies in development to assist patients in achieving significant weight loss," stated Louis Aronne, MD, Clinical Professor of Medicine and Director of the Comprehensive Weight Control Program at New York-Presbyterian Hospital/Weill Cornell Medical Center and one of the investigators involved in the clinical trials. "People with weight problems have a truly biologic disease, and we are in desperate need of more options and effective tools to help our patients combat this disease and the other serious medical conditions that arise as a result of weight gain. I am encouraged by the efficacy and safety seen in these late stage Qnexa trials."

October 9, 2009 (Newswise) - According to new research from the Monell Center and the Mount Sinai School of Medicine, certain common herbicides and lipid-lowering fibrate drugs act in humans to block T1R3, a nutrient-sensing taste receptor also present in intestine and pancreas.Commonly used in agriculture and medicine, these chemical compounds were not previously known to act on the T1R3 receptor.

September 30, 2009 (Newswise) - Treating pregnant women for mild gestational diabetes resulted in fewer cesarean sections and other serious birthing problems associated with larger than average babies, according to a study conducted in part at the University of North Carolina at Chapel Hill.'This study is important because it clearly indicates the value to mothers and their newborns of screening for and treatment of diabetes-like conditions provoked by pregnancy," said John M. Thorp, M.D., McAllister distinguished professor of obstetrics and gynecology at the UNC School of Medicine and a co-author of the study.

"Our work resolves a 40-year controversy in women's health and should be immediately helpful to both pregnant women and the clinicians caring for them."

The study is published in the Oct. 1 issue of the New England Journal of Medicine. The lead author and principal investigator is Mark B. Landon, M.D. of Ohio State University. It was conducted at 14 sites that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network.

About 4 percent of all pregnant women in the U.S. develop gestational diabetes, resulting in about 135,000 cases each year, Thorp said. Because these women have high blood sugar levels, their babies receive more blood glucose than they need, and the extra energy is stored as fat. These babies tend to be larger and fatter than average at birth and thus are more likely to be affected by problems associated with larger babies, such as the need for cesarean delivery, damage to their shoulders during birth and a greater risk of becoming obese as children and developing type 2 diabetes as adults.

There has been a longstanding controversy among physicians on the question of whether treating pregnant women with gestational diabetes for their high blood sugar levels would provide worthwhile benefits. Several professional organizations advocate screening, but the 2008 guidelines of the U.S. Preventive Services Task Force concluded there is insufficient evidence to support screening for and treatment of gestational diabetes.

Against this background, the MFMU Network launched a clinical trial to determine if treating mothers for mild gestational diabetes would reduce infant deaths and birth-related complications. A total of 958 women between 24 and 31 weeks of pregnancy were randomized, with 485 receiving treatment (including dietary changes, self blood glucose monitoring and insulin if necessary) and 473 in the untreated group.

There were no infant deaths in the study and no significant differences between the two groups in terms of babies born with problems such as hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia and birth trauma.

However, there were significantly fewer babies in the treatment group to experience unusually large size (7.1 percent vs. 14.5 percent), high birth weight (5.9 percent vs. 14.3 percent), shoulder damage during birth (1.5 percent vs. 4.0 percent) or to require cesarean delivery (26.9 percent vs. 33.8 percent).

In addition, Thorp said, "It's especially intriguing that mothers in the treatment arm gained less weight during pregnancy, experienced fewer preterm births and had fewer cases of preeclampsia than mothers in the untreated group." Preeclampsia is a syndrome marked by a sudden increase in the blood pressure of a pregnant woman after the 20th week of pregnancy, which can be fatal or lead to long-term health problems for mother and baby.

The study concludes that "these findings confirm a benefit to the identification and treatment of women with mild carbohydrate intolerance during pregnancy."

September 29, 2009 (MannKind Corp.) - AFRESA® (insulin human [rDNA origin]) Inhalation Powder is a well-tolerated, ultra rapid acting insulin able to more closely replicate normal glucose suppression than currently available insulins, according to data presented at the 45th Annual Meeting of the European Association for the Study of Diabetes. Results from the open-label, single-dose, three-way crossover study showed thatendogenous glucose production (EGP) was suppressed earlier following AFRESA administration compared with subcutaneous insulin lispro and inhaled Exubera in adult patients with type 2 diabetes. The inability to effectively suppress endogenous glucose production significantly increases the risk of fasting hyperglycemia in individuals with type 2 diabetes."Many people do not appreciate that most of the excess postprandial glucose increase in individuals with diabetes is due to inadequate suppression of endogenous glucose production by the liver," said Jay S. Skyler, M.D., MACP, Professor, Division of Endocrinology, Diabetes, & Metabolism, Associate Director, Diabetes Research Institute, University of Miami Miller School of Medicine. "This study demonstrates that more rapid insulin availability better suppresses EGP."

AFRESA is a novel, ultra rapid acting mealtime insulin therapy with an action profile that mimics meal-related early insulin release. Based on anextensive phase 2/3 clinical program, a New Drug Application (NDA) is currently under review by the U.S. Food and Drug Administration (FDA) requesting approval to market AFRESA Inhalation Powder and the AFRESA Inhaler for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. AFRESA is conveniently administered by oral inhalation.

Study Design and Key Findings
Findings were based on endogenous glucose production (EGP) suppression in 18 insulin-treated subjects with type 2 diabetes mellitus and normal pulmonary function administered 45 U AFRESA administered by inhalation, 12 IU subcutaneous insulin lispro or 4 mg inhaled Exubera. The main study end-point was time to EGP suppression.

EGP suppression occurred earliest with AFRESA, followed by insulin lispro and Exubera (40, 75 and 130 minutes post-dose of the median EGP-time profiles, respectively). Significant differences between insulin lispro and Exubera were observed up to 40 minutes compared with AFRESA (p<0.002) and up to 2 hours for the Exubera-AFRESA comparison (p<0.05). Median total areas over the EGP curve were comparable across groups (1,938, 1,842 and 2,294 µmol/min). Median postprandial blood glucose areas under the curves were 53,343, 50,608 and 54,598 mg/dl·min for AFRESA, insulin lispro and Exubera, respectively.

September 28, 2009 (AADE) - A new study of an extensive database of Medicare and commercial (employee and dependent) member claims revealed that people with diabetes who received diabetes education have lower average health care costs than patients who do not participate in diabetes education. The study is published in the September/October issue of The Diabetes Educator, the journal of the American Association of Diabetes Educators. The study was conducted by Solucia Consulting of Farmington, Conn., and underwritten by a grant from the AADE.Diabetes education is defined as the ongoing process of facilitating the knowledge, skill and ability necessary for diabetes self-care. The diabetes education intervention aims to achieve optimal health status, better quality of life and reduce the need for costly health care. It is most often provided by diabetes educators, who are health care professionals that have specialized training in diabetes care, traditionally drawn from nursing and dietetics and more recently involving pharmacists.

The authors studied three years of claims data (2005-2007) from commercial insurance and Medicare plans that reflect care of 634,645 individuals with diabetes. The researchers compared claims from those who received diabetes education with those who did not.

According to the analysis, commercially insured patients who received diabetes education cost, on average, 5.7 percent less than those who do not receive diabetes education. Medicare patients who participated in diabetes education cost the health care system 14 percent less than Medicare patients who did not participate. Moreover, those who belonged to physician practices that more frequently referred patients for diabetes education had better overall quality care for their diabetes.

To further corroborate these findings, the authors followed 93,674 patients with diabetes for three years--65,191 had private insurance and 28,483 were Medicare recipients. The researchers then separated those who received diabetes education from those who did not and applied a statistical analysis to this group based on the payments each group's claims generated.

In the commercial population, the average cost of the group that did not receive diabetes education increased at 7.9% annually, compared with 3.3% for the group that received diabetes education. Similarly, the Medicare group that did not receive education experienced average annual increases in cost of 18.2%, compared with 14.5% for the group with diabetes education.

"The study shows that collaboration between diabetes educators and physicians yields positive clinical quality and cost savings," said lead researcher Ian Duncan of Solucia. "If referral rates to diabetes educators are increased, both cost and quality will be improved.

"The current discussion around healthcare reform is about bending the cost curve, and what this study has shown is that patients who are using diabetes education are already experiencing a significant bending of the cost curve" Duncan concluded.

September 25, 2009 (FDA) - FDA is revising the prescribing information for Januvia (sitagliptin) and Janumet (sitagliptin/metformin) to include information on reported cases of acute pancreatitis in patients using these products.Sitagliptin, the first in a new class of diabetic drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Eighty-eight post-marketing cases of acute pancreatitis, including two cases of hemorrhagic or necrotizing pancreatitis in patients using sitagliptin, were reported to the Agency between October 16, 2006 and February 9, 2009. Based on these reports, FDA is working with the manufacturer of sitagliptin and sitagliptin/metformin to revise the prescribing information to include:

• Information regarding post-marketing reports of acute pancreatitis, including the severe forms, hemorrhagic or necrotizing pancreatitis.
• Recommending that healthcare professionals monitor patients carefully for the development of pancreatitis after initiation or dose increases of sitagliptin or sitagliptin/metformin, and to discontinue sitagliptin or sitagliptin/metformin if pancreatitis is suspected while using these products.
• Information noting that sitagliptin has not been studied in patients with a history of pancreatitis. Therefore, it is not known whether these patients are at an increased risk for developing pancreatitis while using sitagliptin or sitagliptin/metformin. Sitagliptin or sitagliptin/metformin should be used with caution and with appropriate monitoring in patients with a history of pancreatitis.

This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

September 23, 2009 (EurekAlert) - MIT engineers have designed a retinal implant for people who have lost their vision from retinitis pigmentosa or age-related macular degeneration, two of the leading causes of blindness. The retinal prosthesis would help restore some vision by electrically stimulating the nerve cells that normally carry visual input from the retina to the brain.Why it matters: The chip would not restore normal vision but could help blind people more easily navigate a room or walk down a sidewalk. "Anything that could help them see a little better and let them identify objects and move around a room would be an enormous help," says Shawn Kelly, a researcher in MIT's Research Laboratory for Electronics and member of the Boston Retinal Implant Project.

How it works: Patients who received the implant would wear a pair of glasses with a camera that sends images to a microchip attached to the eyeball. The glasses also contain a coil that wirelessly transmits power to receiving coils surrounding the eyeball. When the microchip receives visual information, it activates electrodes that stimulate nerve cells in the areas of the retina corresponding to the features of the visual scene. The electrodes directly activate optical nerves that carry signals to the brain, bypassing the damaged layers of retina.

Next steps: The research team, led by John Wyatt, MIT professor of electrical engineering and computer science, recently reported a new prototype that they hope to start testing in blind patients within the next three years, after some safety refinements are made. Once human trials begin and blind patients can offer feedback on what they're seeing, the researchers will learn much more about how to configure the algorithm implemented by the chip to produce useful vision.

September 23, 2009 (EurekAlert) - The commercial failure of Exubera® (Pfizer, New York, NY), the first inhaled insulin product to come to market, led other companies such as Eli Lilly-Alkermes to halt studies of similar drug delivery in development intended to compete for a share of the lucrative diabetes market. Does this signal defeat for efforts to deliver insulin via the lungs? The science and circumstances behind the Lilly-Alkermes decision to discontinue trials of the AIR® inhaled insulin product are explored in a special supplement to Diabetes Technology & Therapeutics, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com). The supplement is available free online at www.liebertpub.com/diaThe supplement presents the data on AIR inhaled insulin that has been made available by Eli Lilly (Indianapolis, IN) and Alkermes (Cambridge, MA), co-developers of the drug. Eight articles describe various protocols in which the effectiveness and safety of AIR were compared to traditional insulin injections in patients with type 1 or type 2 diabetes. These studies represent noninferiority trials, in which AIR was evaluated for its potential to be at least as safe and effective as subcutaneous (SC) insulin across a range of parameters.

Satish K. Garg, MD, Professor of Medicine and Pediatrics at the University of Colorado Denver, and Editor-in-Chief of Diabetes Technology & Therapeutics, and colleagues report the results of a 2-year Phase 3 trial conducted in 385 patients, in an article entitled, "Two-Year Efficacy and Safety of AIR Inhaled Insulin in Patients with Type 1 Diabetes: An Open-Label Randomized Controlled Trial." The study found AIR to be inferior to SC insulin (in a noninferiority clinical trial design) in its ability to maintain optimal blood glucose levels over time, based on measurements of glycosylated hemoglobin (HbA1c).

Similarly, Angel L. Comulada, MD, FACE, Instituto de Endocrinología, Diabetes & Metabolismo, Toa Baja, Puerto Rico, and coworkers demonstrated inferiority of AIR in their study of 500 patients with type 1 diabetes over 6 months. They report their findings in the article "Efficacy and Safety of AIR Inhaled Insulin Compared to Insulin Lispro in Patients with Type 1 Diabetes Mellitus in a 6-Month, Randomized, Noninferiority Trial."

"The question now remains whether this route of delivering insulin has been exhausted or if it still remains to be explored," write Satish Garg, MD and William Kelly, BS from the University of Colorado Denver in the Editorial "Insulin Delivery via Lungs-Is It Still Possible?" MannKind Corporation recently filed a New Drug Application with the FDA for Technosphere® Insulin. It offers faster onset of action with lower postprandial blood glucose excursions especially in the first two hours and is weight neutral, according to the Editorial.

September 23, 2009 (EurekAlert) - Insulin resistance, the hallmark of type 2 diabetes and a condition often associated with obesity, is paradoxically also an apparent contributor to muscle wasting and severe fat loss that accompanies some cancers, according to new research.And in an animal study, a diabetes drug that promotes insulin sensitivity slowed the progression of muscle wasting and fat loss, the main consequences of a syndrome called cachexia, in mice with colon cancer tumors.

Though it remains unknown whether that drug, rosiglitazone, has potential to prevent cachexia in humans with cancer, the finding led researchers to believe that curbing insulin resistance in cancer patients could improve their quality of life.

Research suggests that cachexia is responsible for between one-fifth and one-third of all cancer deaths.

The insulin resistance and cachexia both appear to be connected to inflammation induced either by tumors themselves or by secretions from tumors that activate an immune response, the researchers say.

"Insulin resistance usually follows obesity. In this case, it precedes uncontrollable fat loss," said Martha Belury, senior author of the study and a professor of human nutrition at Ohio State University. "The insulin resistance is the process we've identified that occurs soon after tumors form. So if we can change that part of the disease, we might be able to change the progression and trajectory of how fast fat and muscle are lost as well. That's our goal."

The research appears online and is scheduled for future print publication in the International Journal of Cancer.

Belury and colleagues conducted two experiments. In the first, the researchers sought to demonstrate that animals developed insulin resistance shortly after they developed cancer and before muscle and fat loss became evident. In the second, they tested the effectiveness of the insulin sensitizing drug rosiglitazone against that same tendency toward insulin resistance.

The scientists injected mice with colon cancer cells to mimic one of several digestive-system cancers strongly associated with the development of cachexia. Less than two weeks after the cancer started growing, these mice had become insulin resistant. Control mice without tumors had normal insulin sensitivity. Insulin resistance means that the presence of insulin does not initiate the transfer of sugar, or glucose, from the blood into the tissues, where it is used for energy.

Just three days later, the mice with cancer weighed, on average, 20 percent less than control mice with no tumors; weight loss of at least 5 percent is considered to be a sign of cachexia in humans. By day 19, the total muscle weight in mice with cancer decreased by 29 percent and the weight of their fat tissue dropped by 73 percent. Such rapid loss of muscle and fat indicated these mice had indeed developed cachexia.

"These data provide evidence that in mice with colon cancer tumors, insulin resistance may be involved in the development of cachexia rather than occur as a result of cachexia," Belury said. "And the key here is that people and animals with cachexia do not want to be losing weight. They can eat more and it doesn't matter. There's something internally that's driving this fat and muscle loss."

In the second study, the scientists tested whether rosiglitazone could "rescue" the insulin resistance in mice with colon cancer.

In this study, mice were fed a high-fat diet and randomized into three groups: mice with and without tumors receiving a saline solution as a control, and mice with tumors treated with daily injections of rosiglitazone.

Within eight days, the mice with cancer receiving the rosiglitazone showed more sensitivity to insulin than did the mice with tumors that received no medication. The insulin sensitivity of the medicated mice matched that of mice without tumors.

Similarly, the mice receiving rosiglitazone actually gained weight in this study, as did the mice without tumors. The mice with tumors receiving no treatment lost fat tissue, suggesting they were experiencing the onset of cachexia - despite the high-fat diet they were eating.

In addition to stopping fat and muscle loss, the rosiglitazone also dramatically reduced two biological markers present when proteins break down, particularly in muscles, and a third marker that indicates cells are eating their own amino acids in an attempt to survive.

"We found that those markers of protein and muscle degradation are increased in mice with cachexia, and then when we gave them rosiglitazone, that significantly slowed that degradation," Belury said.

It's too soon to know whether the same drug would have the same effect on humans with cancer, Belury noted. Not all people with cancer develop cachexia, and it's difficult to catch cachexia before severe weight loss has already occurred. And by the time muscles begin to break down, the entire body reacts to the release of amino acids, meaning treatment at that time would have to take such reactions into account.

"For this research, we wanted to catch cachexia as it was having an influence on muscle wasting without the wasting muscle having an influence back on the cachexia," Belury said.

In future studies, the scientists plan to further test the timing and dosage of rosiglitazone and other insulin sensitizers to see if the experiments produce a "prominent, universal effect," Belury said.

September 17, 2009 (Novartis) - The US Food and Drug Administration (FDA) has approved Valturna® (aliskiren and valsartan) tablets, the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosterone system (RAAS), an important regulator of blood pressure. This is the first approval for Valturna, which is indicated for the treatment of high blood pressure in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals."This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren," said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. "It offers an important additional treatment option for physicians and hypertension patients, many of whom are not at their blood pressure goal. Valturna builds upon our strong cardiovascular franchise and is consistent with our long-term commitment to developing effective and innovative therapies. It further strengthens our growing portfolio of single-pill combinations to treat high blood pressure."

Valturna combines in a single pill valsartan, the active ingredient in Diovan®, the number one selling blood pressure medication worldwide, and aliskiren, the active ingredient in Tekturna®, the only approved direct renin inhibitor (DRI). Valturna offers significantly greater blood pressure reduction than either valsartan or aliskiren alone.

"When it comes to diagnosing and treating high blood pressure, there is a real need for innovative therapies that help patients get to a healthier blood pressure range," said John Flack, M.D., Valturna investigator, and Chairman of the Department of Internal Medicine, Wayne State University, Detroit. "Now for the first time, we have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients."

This approval was primarily based on a pivotal eight-week randomized, double-blind, placebo-controlled clinical trial in approximately 1,800 patients, which studied aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. The initial doses of aliskiren and valsartan were 150 mg and 160 mg, respectively, and were increased at four weeks to 300 mg and 320 mg, respectively. Blood pressure reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the 8-week primary endpoint. Mean systolic and diastolic blood pressure reductions from baseline were 17.2/12.2 mmHg for aliskiren 300 mg/valsartan 320 mg, compared with 12.8/9.7 mmHg for valsartan 320 mg, 13.0/9.0 mmHg for aliskiren 300 mg, and 4.6/4.1 mmHg for placebo (p<0.05 for aliskiren/valsartan vs monotherapies or placebo).

The single-pill combination Valturna targets the RAAS in two ways. Valsartan blocks, at the receptor level, the action of angiotensin II, a component of the RAAS that causes blood vessels to tighten and narrow. Aliskiren directly inhibits renin, an enzyme produced by the kidneys that starts a process that leads to formation of angiotensin II. An overactive RAAS may contribute to high blood pressure. By targeting two key points within the RAAS, Valturna helps blood vessels relax and widen so blood pressure is lowered.

Research suggests that up to 85% of patients with high blood pressure may need multiple medications to help control their blood pressure, underscoring the need for effective combination treatments.
High blood pressure affects over one billion individuals globally[ and is a major risk factor for cardiovascular disease, the number one leading cause of death worldwide. If left untreated, patients with high blood pressure are at risk of cardiovascular events such as stroke, heart attack and heart failure, and of organ damage including kidney failure and vision problems. Up to 65% of patients with high blood pressure do not have the condition under control.