Alzheimer's Symptoms, Lesions Reduced By Vitamin B3

An over-the-counter vitamin in high doses prevented memory loss in mice with Alzheimer's disease, and UC Irvine scientists now are conducting a clinical trial to determine its effect in humans.



Nicotinamide, a form of vitamin B3, lowered levels of a protein called phosphorylated tau that leads to the development of tangles, one of two brain lesions associated with Alzheimer's disease. The vitamin also strengthened scaffolding along which information travels in brain cells, helping to keep neurons alive and further preventing symptoms in mice genetically wired to develop Alzheimer's.



"Nicotinamide has a very robust effect on neurons," said Kim Green, UCI scientist and lead author of the study. "Nicotinamide prevents loss of cognition in mice with Alzheimer's disease, and the beauty of it is we already are moving forward with a clinical trial."



The study appears online Nov. 5 in the Journal of Neuroscience.



Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions.



Nicotinamide belongs to a class of compounds called HDAC inhibitors, which have been shown to protect the central nervous system in rodent models of Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. Clinical trials are underway to learn whether HDAC inhibitors help ALS and Huntington's patients.



In the nicotinamide study, Green and his colleague, Frank LaFerla, added the vitamin to drinking water fed to mice. They tested the rodents' short-term and long-term memory over time using water-maze and object-recognition tasks and found that treated Alzheimer's mice performed at the same level as normal mice, while untreated Alzheimer's mice experienced memory loss.



The nicotinamide, in fact, slightly enhanced cognitive abilities in normal mice. "This suggests that not only is it good for Alzheimer's disease, but if normal people take it, some aspects of their memory might improve," said LaFerla, UCI neurobiology and behavior professor.



Scientists also found that the nicotinamide-treated animals had dramatically lower levels of the tau protein that leads to the Alzheimer's tangle lesion. The vitamin did not affect levels of the protein beta amyloid, which clumps in the brain to form plaques, the second type of Alzheimer's lesion.



Nicotinamide, they found, led to an increase in proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. When this scaffolding breaks down, the brain cells can die. Neuronal death leads to dementia experienced by Alzheimer's patients.



"Microtubules are like highways inside cells. What we're doing with nicotinamide is making a wider, more stable highway," Green said. "In Alzheimer's disease, this highway breaks down. We are preventing that from happening."







LaFerla and Green are affiliated with the Institute for Brain Aging and Dementia, which is conducting the clinical trial with funding from the Alzheimer's Association.



The institute seeks volunteers who have been diagnosed with Alzheimer's, are 50 or older, and have a friend or relative who can accompany them to clinic visits and answer questions. Study participants will take the vitamin supplement or a placebo twice daily for 24 weeks, with seven visits to the UCI clinic.



UCI scientists Joan Steffan, Hilda Martinez-Coria, Xuemin Sun, Steven Schreiber and Leslie Thompson also worked on the study, which was supported in part by the Alzheimer's Drug Discovery Foundation and the National Institutes of Health.



About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students and nearly 2,000 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.6 billion.

ORVACS Phase II Study Combines Immunomodulatory Intervention With Interleukin-7 And Antiretroviral Intensification With Raltegravir To Attack HIV

ORVACS (Objectif Recherche VACcin Sida) has launched a Phase II study designed to test the hypotheses that combination therapy with potent antiviral agents and immunomodulator can lead to a decrease in the HIV viral reservoirs and, ultimately, to eradication of the virus. The study is currently being conducted at clinical sites in France, Spain, Italy and the United Kingdom.



Known as ERAMUNE 01, the Phase II clinical trial is scientifically coordinated by Christine Katlama as Principal Investigator, Brigitte Autran, Vincent Calvez and Dominique Costagliola from the University Pierre et Marie Curie and will use Cytheris' investigative immunomodulatory agent, recombinant human interleukin-7 (CYT107), in combination with two potent antiretroviral drugs represented by the integrase inhibitor, raltegravir (ISENTRESS(R) - Merck & Co.) and the CCR5 inhibitor, maraviroc (SELZENTRY(TM) - ViiV Healthcare). The main hypothesis of this study is that by combining the most potent and synergistic antiretroviral drugs, coupled with an immunomodulating agent capable of targeting or inducing activation of latently infected cells, the reservoirs of HIV can be decreased and, in the best case scenario, eradication of the virus may be feasible.



ERAMUNE 01 is sponsored by ORVACS and has been designed by the members of its international scientific advisory board. ORVACS is a non-profit organization based in Paris, France, that is supported and funded by the Bettencourt Schueller Foundation. The mission of ORVACS is to promote and conduct research on therapeutic vaccines and immunotherapeutic approaches in the field of AIDS. Created in 2001, ORVACS has a two-fold objective:


- The development of new therapeutic immunization strategies through clinical trials evaluating the safety, immunogenicity and efficacy of new vaccines


- The pre-clinical development of new anti-HIV vaccine approaches


To optimize and further its mission, ORVACS has created a network of international academic research teams that are leaders in the field of immunology and antiretroviral therapy (ART) and on the development of innovative vaccine strategies against HIV. The objective of this vaccine therapy is to stimulate a weakened immune system and to amplify immune response.



The study is under the direction of Prof. Christine Katlama, MD (Principal Investigator), Head of the AIDS Clinical Research Unit, Department of Infectious Diseases, Hopital Pitie-Salpetriere, Paris, France.



"The novelty of the approach in this study is three-fold," said Prof. Katlama. "First, the use of highly potent antiretroviral therapy combining drugs with different HIV enzyme targets or receptors and different penetrations in cells, to suppress the virus to truly undetectable levels; secondly, the addition of immunomodulatory therapy that specifically targets viral reservoirs; and lastly, the rigorous selection of patients already having a low HIV reservoir as measured by peripheral blood HIV DNA content."



Other participants in the study include Bonaventura Clotet, MD, PhD (co-Principal Investigator), Chief of the Internal Medicine HIV Unit, University Hospital Germans Trias i Pujol, Barcelona, Spain. Additional key participants from the Universit?© Pierre et Marie Curie and the Groupe Hospitalier Piti?©-Salp??tri??re include: Prof. Brigitte Autran, MD, PhD (Immunology); Prof Vincent Calvez, MD, PhD (Virology); and, Dominique Costagliola (Methololody).



The ERAMUNE 01 study, "International, multicenter, randomized, non-comparative controlled study of therapeutic intensification plus immunomodulation in HIV-infected patients with long-term viral suppression," is being conducted in Paris, France (Groupe Hospitalier Piti?©-Salp??tri??re); Milan, Italy (San Raffaele Scientific Institute); Badalona, Spain (Fundacio Irsicaixa); Barcelona, Spain (University Hospital Clinic of Barcelona); and London, United Kingdom (Royal Free Hospital).



Additional information about the study can be found here.

Published Study Shows Benefits Of Diachrome For People With Type 2 Diabetes

Nutrition 21, Inc. (NASDAQ: NXXI) has announced the results of a recent placebo controlled, double-blind, randomized, single center study that demonstrated that Diachrome®, a patented combination of chromium picolinate and biotin, safely improves blood glucose levels and cholesterol metabolism in people with type 2 diabetes. Published in the December issue of Diabetes Technology and Therapeutics, the study supports the role of chromium picolinate - the most studied, highly absorbed and efficacious form of chromium - plus biotin as a safe and effective nutritional adjunct therapy in diabetes care.



The 30-day study examined thirty-six overweight or obese poorly controlled patients with type 2 diabetes taking Diachrome who were already receiving oral anti-diabetic drug(s). The results also showed a significantly greater reduction in the total area under the curve for glucose (AUCg) during the oral glucose tolerance test (OGTT) for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%). Mean fructosamine levels, a measure of the average blood glucose level during a period of three weeks, were also significantly reduced in the treatment group (-1.3 mmol/L) compared to the placebo group (0.7 mmol/L).



"Results from this pilot study promote the potential benefits of supplementing chromium picolinate and biotin with one's daily diabetes care regimen," said Gregory Singer, MD, lead author and cardiovascular medicine specialist at Yale University School of Medicine. "Chromium picolinate with biotin represents an adjunctive strategy to conventional oral diabetes therapy for improved blood sugar control and cholesterol metabolism."



A larger 400 patient, 90-day randomized placebo controlled study to determine the effects of chromium picolinate/biotin on hemoglobin A1c and other risk factors in type 2 diabetes is expected to be published next year.



"Previous studies have demonstrated that chromium picolinate can significantly impact A1c and other critical markers in people with type 2 diabetes," said Dr. Singer. "Additional research currently underway may provide us with further understanding of the supplement's role in the management of type 2 diabetes."



Another study released this month at the 19th World Diabetes Congress meeting in Cape Town, South Africa, demonstrated that supplementing with chromium picolinate, an active ingredient in Diachrome, led to significant improvements in blood sugar levels of people with type 2 diabetes over a six-year period. In addition to existing treatments, 1056 patients with diabetes ages 20 to 90 years old were observed among nine sites before and during supplementation with 500 mcg daily of chromium as chromium picolinate for one to six years. A significant decrease in fasting glucose levels of 4.67 mmol/L and postprandial glucose levels of 5.77 mmol/L was seen in patients taking chromium picolinate. The study showed that blood glucose levels continued to improve each year throughout the six years of the study.
















"This study - one of the largest and longest clinical trials measuring chromium picolinate's effects on blood glucose levels - underscores the nutrition supplement's beneficial role in helping manage type 2 diabetes," said lead investigator Nancy Cheng, MD, PhD, Senior Director of Tang-An Diabetic Clinic and Education Center in Beijing.



Chromax® chromium picolinate, found in Diachrome and used in these studies, has been recognized as safe by many of the world's leading government and academic research institutions, including the U.S. Food & Drug Administration, the Institute of Medicine and the UK's Food Standards Agency. In addition, biotin has been deemed safe by the Food and Drug Administration and is also Generally Recognized as Safe (GRAS) for use in foods and supplements.







About Diachrome



Diachrome is a non-prescription nutrient-based therapy formulated to help support blood glucose management in people with diabetes. It is composed of two safe and beneficial nutrients: chromium (as Chromax® chromium picolinate) and biotin (a B-vitamin). A growing body of scientific evidence indicates that Diachrome's unique ingredient combination has positive effects on insulin function, blood glucose, lipid metabolism and cardiovascular health. The nutritional therapy can be found in retail stores nationwide.



About Nutrition 21



Nutrition 21 is a nutritional bioscience company and the maker of chromium-based and omega-3 fish oil-based supplements with health benefits substantiated by clinical research. The company markets Chromax® chromium picolinate, chromax/, which is the most-studied form of the essential mineral chromium. Chromax, a supplement for healthy and pre-diabetic people that promotes insulin health and helps improve blood sugar metabolism, cardiovascular disease, control carbohydrate cravings and fight weight gain, is now available through food, drug and mass retailers nationwide. Nutrition 21 also developed and markets Diachrome®, diachrome/ , a proprietary, non-prescription, insulin sensitizer for people with type 2 diabetes. It is available in select drug retailers nationwide. Nutrition 21 holds 33 patents for nutrition products and uses, 23 of which are for chromium compounds and their uses. The Company is the exclusive importer of Icelandic fish oils, including omega-3 fatty acids, which are manufactured to pharmaceutical standards and sold under the Iceland Health® brand, icelandhealth.info/. More information is available at Nutrition 21.



Sarah Yeager

Nutrition 21



Chad Hyett

Fleishman Hillard

Despite The Guidelines, Lower Blood Pressure Might Be Unhealthy For Kidney Patients

Recent guidelines by The National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI)1 call for lower target blood pressure levels in patients with chronic kidney disease (CKD). But in the absence of high-quality scientific evidence, there's a chance this recommendation could do more harm than good, according to a special article appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN).


"The new low blood pressure goals are not definitively supported by data, would be costly to the healthcare system and potentially harmful to patients," according to Julia B. Lewis, MD (Vanderbilt University, Nashville, TN), who performed a critical review of the research evidence.


Issued last year, updated national guidelines for CKD treatment call for a target blood pressure level of less than 130/80 mm Hg (millimeters of mercury) to help preserve kidney function. The recommendation was based on observational studies showing "a continuous benefit of reducing blood pressure to lower and lower levels."


However, Lewis points out several problems with the research behind the new guidelines. Most importantly, since patients in the observational studies were not randomly assigned to different blood pressure goals, the apparent benefit of lower blood pressures could result from other "confounding" factors. "The data supporting the current blood pressure guidelines for patients with CKD do not meet the standard of a primary outcome of a randomized trial," says Lewis.


She explains that, as kidney disease worsens, blood pressure rises and becomes harder to control. So the data may simply reflect the fact that patients with less severe kidney disease have lower blood pressure. In studies where patients were randomly assigned to treatments, the benefits of lower blood pressure were seen only in a subgroup of patients, or several years after the end of treatment.


"Also there is other evidence to bring into question the widespread application of this costly goal of a blood pressure less than 130/80 mm Hg," Lewis adds. Some studies have even suggested that CKD patients with very low blood pressure could be at increased risk of death.


A new trial sponsored by the National Institutes of Health (NIH) will compare the effects of different blood pressure targets in over 10,000 patients with CKD. Until the results are available, Lewis believes that doctors should make individualized decisions about blood pressure control for their patients with kidney disease.


Lewis emphasizes that no firm conclusions can be drawn from her review, since it was based on different types of studies with conflicting results.


The study author is a consultant for Thervance Pharmaceuticals, Covance Pharmaceuticals, and Amira Pharmaceuticals. She also receives research support from Keryx Pharmaceuticals, Nephrogenix, Eli Lilly, and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK).


The article, entitled "Blood Pressure Control in Chronic Kidney Disease: Is Less Really More?" will appear online at jasn.asnjournals/ on June 24, 2010, doi 10.1681/ASN.2010030236.


The American Society of Nephrology (ASN) does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.


Founded in 1966, the American Society of Nephrology (ASN) is the world's largest professional society devoted to the study of kidney disease. Comprised of 11,000 physicians and scientists, ASN continues to promote expert patient care, to advance medical research, and to educate the renal community. ASN also informs policymakers about issues of importance to kidney doctors and their patients. ASN funds research, and through its world-renowned meetings and first-class publications, disseminates information and educational tools that empower physicians.


1 K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 7: Pharmacological therapy: Use of antihypertensive agents in CKD. National Kidney Foundation.

Organized Phone Therapy For Depression Found Cost-Effective

When people get brief, structured, phone-based cognitive behavioral psychotherapy soon after starting on antidepressant medication, significant benefits may persist two years after their first session, with only modest rises in cost. Over two years, this treatment is cost-effective, according to a randomized trial in the October 2009 Archives of General Psychiatry.



"The most important reason to treat depression is to reduce suffering and improve daily functioning," said Group Health psychiatrist Gregory E. Simon, MD, MPH, also a senior investigator at Group Health Research Institute (formerly called Group Health Center for Health Studies). "But our findings suggest that insurers or health care systems aiming to improve depression treatment in primary care should consider incorporating structured psychotherapy."



The Journal of the American Medical Association (JAMA) reported earlier results from the same 600-person trial, the largest to date of psychotherapy by phone - and one of the largest studies of psychotherapy ever.



Over two years, phone psychotherapy plus care management led to a gain of 46 depression-free days, with only a $397 increase in outpatient health care costs. The incremental net benefit of phone psychotherapy plus care management was positive, even if a day free of depression was valued as low as $9.



By contrast, phone care management alone, with no phone psychotherapy, led to a gain of only 29 days free of depression, with a $676 rise in outpatient health care costs. The incremental net benefit of phone care management alone was negative, even if a day free of depression was valued up to $20.



The trial enrolled 600 Group Health patients whose primary care doctors diagnosed their depression and (as is usual in primary care) prescribed their antidepressants without psychotherapy.



The patients were randomly assigned to receive either:
Usual primary care


Phone care management: usual care plus a phone-based care-management program including three outreach calls from a bachelors-level clinician (assessing patients' symptoms, antidepressant drug use, and side effects and referring to mental health specialty care if needed), with care coordination and feedback to the primary care doctor


Phone psychotherapy: usual care, plus phone care management, plus eight 30-40 minute sessions of structured cognitive-behavioral psychotherapy delivered by phone by a masters-level mental health clinician

The trial excluded people who were already seeing a therapist or intending to do so. The patients and mental health clinicians never met face to face, only over the phone. The mental health clinicians followed a structured protocol for psychotherapy. They encouraged the patients to identify and counter their negative thoughts (cognitive behavioral therapy), pursue activities they had enjoyed in the past (behavioral activation), and develop a plan to care for themselves.



Few of the patients who received phone-based therapy - even fewer than those who did not receive it - sought in-person therapy. Phone-based therapy is more convenient and acceptable to patients than in-person psychotherapy, said Dr. Simon.



Depression symptoms, including feeling discouraged and avoiding other people, can prevent people from seeking help, he added. Nationally, only about half of insured patients receiving depression treatment make any psychotherapy visit, and less than a third make four or more visits. By contrast, in this trial, three in four patients completed at least six phone therapy sessions.



The National Institute of Mental Health funded the trial. The other authors were Evette J. Ludman, PhD, senior research associate, and Carolyn M. Rutter, PhD, senior investigator at Group Health Research Institute.

Steroid Nasal Sprays Relieve Sinusitis Symptoms, Review Finds

Every year, nearly 37 million Americans suffer from the sinus pressure, nasal congestion, cough and postnasal drip that accompany sinusitis.


Doctors often prescribe antibiotics to relieve acute sinusitis, which can develop following a chest cold. However, steroid nasal sprays either alone or with antibiotic therapy may better ease symptoms and speed recovery, suggests a new review by Israeli researchers.


Sinusitis is an inflammation of the mucous membranes that line the sinus cavities. Steroid sprays like Flonase, Nasonex and Rhinocort, which work by reducing inflammation to promote drainage in the sinuses, are often prescribed to treat chronic sinusitis and allergies symptoms.


But the use of steroids sprays for acute sinusitis is not as universally accepted.


In this review, Anca Zalmanovici, a family physician at Rabin Medical Center in Petach Tikva, and her co-author analyzed data from four randomized controlled trials including nearly 2,000 participants, all with clinical symptoms of acute sinusitis.


The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.


Two of the studies evaluated patients at treatment centers in the United States, one took place in Turkey and the other included 71 medical centers in 14 countries.


Study participants, who underwent X-rays or nasal endoscopy to confirm diagnosis, received either a placebo or intranasal corticosteroids for two or three weeks, alone or in combination with antibiotics. Intranasal corticosteroids used included fluticasone propionate (Flonase), mometasone furoate (Nasonex) and budesonide (Rhinocort).


Overall, 73 percent of the patients treated with nasal steroids experienced relief or marked improvement of symptoms during the study period, compared with only 66.4 percent of patients who received the placebo.


"For every 100 patients treated with intranasal corticosteroids, seven additional patients had complete or marked symptom relief," compared to those in the placebo group, the reviewers found.


Researchers pooled data from three of the four studies, excluding the lowest-quality study from the statistical analysis.















None of the studies reported serious side effects, and rates of sinusitis relapse were similar between the treatment and placebo groups.


Stronger doses of nasal steroids appeared to work better. Patients receiving daily doses of 400 micrograms were more likely to experience relief of sinusitis symptoms, than were patients receiving 200-microgram doses.


Although there is not enough evidence to suggest that nasal steroids can stand alone for acute sinusitis treatment, "the results of these studies and reviews support the current clinical rationale of adding an intranasal corticosteroid to antibiotic therapy," reviewers say.


Allen Seiden, M.D., director of the University of Cincinnati Taste and Smell Center, said that more data are required before routine recommendations on intranasal corticosteroids can be made.


"It seems to have been a well-conducted review, with thorough statistical analysis. However, in the end, it analyzed relatively few studies," Seiden said.


He added that the review lacked information about how individual diagnoses were made, and said that even with X-rays and nasal endoscopy, distinguishing between viral and bacterial infections can be difficult, a problem that may influence the choice of treatment.


When it comes to treating sinus infections, "patients vary as to when they will seek medical intervention. Some will come in after only a day or two of symptoms; some not for two to three weeks," Seiden said. Longer waits can make symptoms harder to treat, he said, "while many patients with symptoms for only a few days will in fact have a viral infection."


Although there are few downsides to using nasal steroids such as those in the review they are fairly expensive, Seiden said. According to the National Institute of Allergy and Infectious Diseases, diagnosing and treating sinusitis costs Americans nearly $6 billion every year.


Zalmanovici A, Yaphe J. Steroids for acute sinusitis (Review). Cochrane Database of Systematic Reviews 2007, Issue 2.


The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit cochrane for more information.


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Washington, DC 20009

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View drug information on Flonase Nasal Spray; Nasonex Nasal Spray; Rhinocort Aqua Nasal Spray.

Amgen Highlights Data To Be Presented At American Society Of Hematology Annual Meeting

Amgen (Nasdaq: AMGN) announced that it will present data from several key Nplate® (romiplostim) studies at the 52nd Annual Meeting and Exposition of the American Society of Hematology (ASH), Dec. 4-7, 2010, in Orlando, Fla. Results from six studies evaluating Nplate in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) add to the growing body of data supporting the use of Nplate in this setting, including the final efficacy and safety results from the largest and longest study of Nplate in adult chronic ITP. Amgen will also present data for other marketed products including Neulasta® (pegfilgrastim) and Aranesp® (darbepoetin alfa).


"The complete results from a 5-year open-label extension study of Nplate in the adult chronic ITP setting show that Nplate increases and sustains platelet counts in these patients and that adverse event rates were consistent with those reported in previous studies," said Sean Harper, M.D., senior vice president, Global Development and Chief Medical Officer at Amgen. "This is the largest and longest study of Nplate in this setting, and reinforces the potential of Nplate as a long-term treatment option."


Amgen also announced the expansion of its Neulasta FIRST STEP® Program to its newly established co-pay coupon umbrella program, the Amgen FIRST STEP™ Program for commercially insured patients. The Amgen FIRST STEP™ Program will feature the Nplate FIRST STEP™ Program and Neulasta FIRST STEP® Programs. The Amgen FIRST STEP™ Program is significant among oncology commercial co-pay coupon programs, as it is the first program under the medical benefit with no income eligibility requirement. The program is intended to help eligible patients meet their deductible, co-insurance, and/or co-payment requirements under the medical benefit for Neulasta and Nplate. Under this program, eligible patients will incur no out of pocket costs for their first Nplate or Neulasta treatment associated with a new treatment regimen and will pay a maximum of $25 for subsequent injections.


SELECTED ABSTRACTS OF INTEREST INCLUDE:


Nplate ITP Data



-- Long-Term Efficacy and Safety of Romiplostim Treatment of Adult Patients with Chronic Immune Thrombocytopenia (ITP): Final Report from an Open-Label Extension Study


(Abstract No. 68; Oral Presentation; Sunday, Dec. 5, 4:45 p.m. EST, room 230)



-- The Effects of Romiplostim or Standard of Care (SOC) on Splenectomy and Treatment Failure of Patients Who Had Immune Thrombocytopenia (ITP) for Less Than or Equal to One Year


(Abstract No. 3702; Poster III-481; Monday, Dec. 6, 6:00 p.m.-8:00 p.m. EST, Hall A3/A4)
















-- Analysis of Mortality Rates During Romiplostim Clinical Studies of Patients (Pts) with Immune Thrombocytopenia (ITP)


Abstract No. 3701; Poster III-480; Monday, Dec. 6, 6:00 p.m.-8:00 p.m. EST, Hall A3/A4)



-- Patient Quality of Life (QoL) in Nonsplenectomized Immune Thrombocytopenia (ITP) Patients Receiving Romiplostim or Medical Standard of Care (SOC)


(Abstract No. 569; Oral Presentation; Monday, Dec. 6, 3:45 p.m. EST, Room 340)



-- Evaluation of Romiplostim in a Randomized Placebo-Controlled Phase 3 Study of a Japanese Population with Chronic Immune Thrombocytopenia (ITP)


(Abstract No. 3704; Poster III-483; Monday, Dec. 6, 6:00 p.m.-8:00 p.m. EST, Hall A3/A4)



-- Impact Assessment of Immunogenicity of Romiplostim in Subjects with Immune Thrombocytopenic Purpura (ITP)


Abstract No. 2517; Poster II-397; Sunday, Dec. 5, 6:00 p.m.-8:00 p.m. EST, Hall A3/A4)


Nplate MDS Data



-- Update from an Open-Label Extension Study Evaluating the Long-Term Safety and Efficacy of Romiplostim in Thrombocytopenic Patients (Pts) with Myelodysplastic Syndromes (MDS)


(Abstract No. 1885; Poster I-865; Saturday, Dec. 4, 5:30 p.m.-7:30 p.m. EST, Hall A3/A4)



-- Associations Between Platelet Count and Survival and Disease Progression in Thrombocytopenic Patients with Myelodysplastic Syndromes


Abstract No. 2905; Poster II-785; Sunday, Dec. 5, 6:00 p.m. EST, Hall A3/A4)


Neulasta



-- Pegfilgrastim Use Associated with Lower Risk of Hospitalization Than Filgrastim Use: A Retrospective US Claims Analysis


(Abstract No. 3801; Poster III-580; Monday, Dec. 6, 6:00 PM-8:00 p.m. EST, Hall A3/A4)



-- Underreporting of Myelotoxicity with Emerging Regimens for Selected Hematologic Malignancies


(Abstract No. 1501; Poster I-481; Saturday, Dec. 4, 5:30 p.m.-7:30 p.m. EST, Hall A3/A4)



-- Clinic Staff Time and Labor Costs Associated with Administering Pegfilgrastim as Compared with Filgrastim to Patients Receiving Myelosuppressive Chemotherapy: Results of a Health Economic Model


(Abstract No. 1515; Poster I-495; Saturday, Dec. 4, 5:30 p.m.-7:30 p.m. EST, Hall A3/A4)


Aranesp



-- Real-Life Cost Analysis of Anemia Treatment with Erythropoiesis Stimulating Agents In Cancer Patients Receiving Chemotherapy


(Abstract No. 3811; Poster III-590; Monday, Dec. 6, 6:00 p.m.-8:00 p.m. EST, Hall A3/A4)


About Adult ITP


In patients with ITP, platelets blood elements needed to prevent bleeding are destroyed by the patient's own immune system. Recent data also suggest that low platelet counts in the blood may be caused by the inability of the body's natural processes to produce platelets. Low platelet counts leave adult ITP patients open to sudden serious bleeding events. The risk for serious bleeding events increases when platelet counts drop to less than 30,000 platelets per microliter; normal counts range from 150,000 to 400,000 platelets per microliter. ITP has historically been considered a disease of platelet destruction although recent data suggest that the body's natural platelet production processes in ITP are unable to compensate for low levels of platelets in the blood. Increasing the rate of platelet production may address low platelet levels associated with ITP.


Some other available treatments (e.g., corticosteroids, immunoglobulins) are often unsuitable for long-term use due to tolerability issues and poor predictability of response. Surgical therapy (removal of the spleen) can be an option for many adult patients with chronic ITP, but does not work in all cases, and can be contraindicated in certain cases. Currently, there are approximately 90,000 adult chronic ITP patients in Europe and the United States (U.S.). ITP affects about twice as many adult women as men.


About Nplate


Nplate is the first platelet producer approved in the European Union (EU), Canada, Australia, Russia, Switzerland, Mexico and the U.S. Nplate also has received orphan designation for chronic ITP in the U.S. (2003), the EU (2005), Switzerland (2005), Japan (2006) and Mexico (2010).


Nplate is the first FDA approved treatment specifically for adult chronic ITP. It is also being investigated for potential use in children ages 12 months to 18 years old with persistent severe thrombocytopenia, myelodysplastic syndromes (MDS) and chemotherapy-induced thrombocytopenia (CIT).


In the U.S., Nplate is indicated for the treatment of thrombocytopenia in patients with chronic immune ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding. Nplate should not be used in an attempt to normalize platelet counts.


In the EU, Nplate is indicated for the treatment of splenectomized adult chronic ITP patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Nplate may be considered as a second-line treatment for adult non-splenectomized ITP patients for whom surgery is contraindicated.


Nplate was named as a recipient of the U.S. Prix Galien 2009 "Best Biotechnology Product" award and also received the 2009 Scrip Awards for "Best New Drug." Nplate has also been honored with numerous awards throughout the EU, including a 2010 Prix Galien in France in the category of "Drugs for Rare Diseases." In September 2010, Nplate was awarded the 2010 International Prix Galien Award, an award granted every two years which recognizes the "best of the best" selected from previous national Prix Galien award recipients.


Important U.S. Nplate Safety Information


Serious adverse reactions associated with Nplate in clinical studies were bone marrow reticulin deposition and worsening thrombocytopenia after Nplate discontinuation. Additional risks include bone marrow fibrosis, thrombotic/thromboembolic complications, lack or loss of response to Nplate, and hematological malignancies and progression of malignancy in patients with a pre-existing hematological malignancy or MDS. Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.


In the U.S., Nplate is available only through a restricted distribution program called Nplate® NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program.


In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction.


Important EU Nplate Safety Information


The most common side effects are headache, fatigue, arthralgia, myalgia, injection site bruising, injection site pain, oedema peripheral, dizziness, muscle spasms, nausea, contusion, diarrhea, bone marrow disorder, influenza-like illness, insomnia and pruritus.


Reoccurrence of thrombocytopenia and bleeding after cessation of treatment and increased bone marrow reticulin have been associated with Nplate treatment in the clinical trials. Thrombotic/thromboembolic complications, progression of existing hematopoietic malignancies or MDS, and effects on red and white blood cells are all potential risks associated with Nplate treatment. As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein.


About Neulasta and NEUPOGEN®


Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.


Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.


NEUPOGEN (filgrastim) is indicated to decrease the incidence of infection' as manifested by febrile neutropenia' in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.


Please refer to the Important European Product Safety Information section for approved indications in the EU.


Important U.S. Product Safety Information


Do not administer Neulasta or NEUPOGEN to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim. NEUPOGEN is contraindicated in patients with known hypersensitivity to E. coli-derived proteins, such as filgrastim.


Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta or NEUPOGEN. Permanently discontinue Neulasta or NEUPOGEN in patients with serious allergic reactions.


Splenic rupture, including fatal cases, can occur following the administration of Neulasta and NEUPOGEN.


Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta or NEUPOGEN.


Alveolar hemorrhage, manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization, has been reported in healthy donors undergoing peripheral blood progenitor cell mobilization, an unapproved use of NEUPOGEN. Hemoptysis resolved with discontinuation of NEUPOGEN.


Bone pain and pain in extremity occurred at a higher incidence in Neulasta-treated patients as compared with placebo-treated patients. In clinical trials involving NEUPOGEN, bone pain was most frequently reported adverse event.


Important European Product Safety Information


For full prescribing information please see the Summary of Product Characteristics for each product.


NEUPOGEN is indicated for reduction in duration of neutropenia and incidence of febrile neutropenia after established cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes); reduction in duration of neutropenia in patients undergoing myeloablative therapy followed by bone marrow transplantation considered to be at increased risk of prolonged severe neutropenia. The safety and efficacy of NEUPOGEN are similar in adults and children receiving cytotoxic chemotherapy. NEUPOGEN is indicated for mobilisation of peripheral blood progenitor cells (PBPCs); long-term treatment to increase neutrophil counts and reduce incidence and duration of infection-related events in patients with severe congenital, cyclic, or idiopathic neutropenia treatment of persistent neutropenia in patients with advanced HIV infection.


NEUPOGEN is contraindicated in patients with hypersensitivity to filgrastim or excipients. Not to be used for escalation of cytotoxic chemotherapy doses above established regimens or administered to patients with severe congenital neutropenia (Kostman's Syndrome) with abnormal cytogenetics.


Administer NEUPOGEN with caution in secondary AML. Safety and efficacy of NEUPOGEN not established in de novo AML patients < 55 years with good cytogenetics (t(8;21), t(15;17) and inv(16)). The onset of pulmonary signs (cough, fever, dyspnoea) in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS). Discontinue NEUPOGEN and give appropriate treatment.


Other adverse events of special importance associated with NEUPOGEN include GvHD and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation, very rare cases of splenic rupture reported in healthy donors and patients, and hypersensitivity-type reactions in cancer patients. NEUPOGEN should be permanently discontinued in patients who experience a serious allergic reaction. NEUPOGEN is not recommended in period 24 hours before to 24 hours after chemotherapy. Neulasta is indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).


Neulasta is contraindicated in patients with hypersensitivity to pegfilgrastim or excipients.


Neulasta should not be used in patients with MDS, CML and secondary AML. The safety and efficacy of Neulasta administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established.


Neulasta should be discontinued following preliminary signs of ARDS. Spleen size should be carefully monitored and caution exercised when administering in patients with sickle cell disease. Safety and efficacy of Neulasta for mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated.


Other adverse events of special importance associated with Neulasta include bone pain, allergic-type reactions including anaphylaxis (pegfilgrastim should be permanently discontinued in patients who experience a serious allergic reaction) and very rare cases of splenic rupture including fatal cases. Neulasta should be administered approximately 24 hours after administration of cytotoxic chemotherapy.


About Aranesp


Aranesp was approved by the FDA in 2001 for the treatment of anemia associated with chronic renal failure (CRF) for patients on dialysis and patients not on dialysis. The European Commission granted marketing authorization for the same indication in 2001 and subsequently updated it for CRF patients with symptomatic anemia in 2008.


In 2002, the FDA approved Aranesp for the treatment of anemia caused by concomitantly administered chemotherapy in patients with nonmyeloid malignancies.


The European Commission authorized the treatment of anemia caused by concomitantly administered chemotherapy in patients with non-haematological malignancies in 2002 and extended it to include non-myeloid malignancies in patients receiving chemotherapy in 2003.


Important U.S. Product Safety Information


Aranesp is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for red blood cell transfusions in patients with metastatic, non-myeloid malignancies. Studies to determine whether Aranesp increases mortality or decreases progression-free/recurrence-free survival are ongoing.



-- Aranesp is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.



-- Aranesp is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of Aranesp on progression-free and overall survival.



-- Aranesp use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.


WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE AND INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE


Cancer:



-- ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.



-- To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.




-- Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense Aranesp, EPOGEN® or PROCRIT® to patients with cancer.



-- Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.



-- ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.



-- Discontinue following the completion of a chemotherapy course.



-- ESAs are contraindicated in patients with uncontrolled hypertension.


Important European Product Safety Information


For full prescribing information please see the Summary of Product Characteristics.


Aranesp is indicated for treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.


Aranesp is contraindicated in patients with poorly controlled hypertension.


Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion.


In controlled clinical studies, use of Aranesp and other ESAs have shown:



-- shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target Hb > 14 g/dL; ESAs are not indicated for use in this patient population

-- shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target Hb 12-14 g/dL

-- increased risk of death when administered to target Hb of 12 g/dl (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy; ESAs are not indicated for use in this patient population.


In some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life-expectancy; the environment in which the patient is being treated; and patient preference.


In patients with solid tumours or lymphoproliferative malignancies, if Hb >12 g/dL, the dose should be reduced/held to minimise the potential risk of thromboembolic events.


Discontinue use after the end of chemotherapy.


Forward-Looking Statements


This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Dec. 2, 2010 and expressly disclaims any duty to update information contained in this news release.


No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.


In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments, domestic and international trends toward managed care and health care cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.


The scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the FDA for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.

ViiV Healthcare Presents New Data From HIV/AIDS Portfolio Demonstrating Research Advances And Commitment To Patient Care At Conference On Retroviruses

At the 17th Conference on Retroviruses and Opportunistic Infections (CROI), ViiV Healthcare presented new data across its broad range of investigational and current medicines for the treatment of HIV/AIDS. Highlighted data at the conference included an oral presentation on the investigational integrase inhibitor, S/GSK1349572, as well as data presentations on SELZENTRY® (maraviroc) and EPZICOM® (abacavir/lamivudine).


"ViiV Healthcare is dedicated to the pursuit of new scientific insights that could help solve complex treatment issues for HIV. We hope that our findings on both our investigational compounds and our available medicines will further enable treatments to be better tailored to the individual patient," stated Dr. Dominique Limet, chief executive officer of ViiV Healthcare. "Beyond currently available therapies, there remains a substantial need for new and effective treatment options. We are committed to advancing S/GSK1349572, as integrase inhibitors represent an important new class of medications for treating patients with HIV."


Overall, more than 24 abstracts were presented during the conference relating to ViiV Healthcare's current medicines and pipeline. These presentations underscore the company's commitment to enhancing its knowledge base for its current medicines, tackling major challenges in treating HIV/AIDS, and providing patients and physicians with data that can lead to more informed prescribing decisions. Highlights from the presentations on S/GSK1349572, SELZENTRY, and EPZICOM are described below.


Data Presentations on S/GSK1349572


An oral presentation described the innovative and rational design approach that led to the identification of a potent series of HIV-1 integrase inhibitors, including the lead clinical candidate, S/GSK1349572. In vitro studies of S/GSK1349572 across a range of subtypes suggest that S/GSK1349572 displays potent antiviral activity to wild type-virus and key integrase inhibitor-resistant HIV. S/GSK1349572 was additive or synergistic, with no observed antagonism of antiviral activity with approved drugs from all classes. The preclinical attributes were confirmed in a Phase IIa study during which HIV-infected subjects receiving S/GSK1349572 50mg alone once daily for 10 days had a mean reduction in HIV-1 of 2.5 log10 c/mL.


In vitro data presented on the resistance profile of S/GSK1349572 suggest that S/GSK1349572 demonstrates activity against site-directed molecular clones generated primarily based on raltegravir (RAL) and elvitegravir (ELV) resistant viruses observed in clinical trials. These data suggest that S/GSK1349572 has a resistance profile distinct from raltegravir and elvitegravir. ViiV Healthcare continues to characterize the resistance profile of S/GSK1349572 in clinical studies.















Additionally, data from a Phase I study suggest that S/GSK1349572 administered in combination with atazanavir (ATV) or ATV/ritonavir (RTV) results in S/GSK1349572 exposure levels that do not require dose adjustment and was generally well tolerated in healthy adult subjects. No clinically significant trends in laboratory values, vital signs, or electrocardiograms (ECGs) were observed during study drug dosing. All adverse events (AEs) were mild or moderate, and no subject withdrew from the study due to an AE. The most common drug related AE observed during treatment with S/GSK1349572 alone was nausea (2/24, 8 percent). The most common AE during concomitant therapy was ocular icterus (11/24, 46 percent). Increased bilirubin was observed only during concomitant ATV dosing. Co-administration with ATV or ATV/RTV increased plasma S/GSK1349572 exposure with a more prominent effect from ATV alone.


Further study is necessary to determine conclusively the efficacy, safety, and resistance profile of S/GSK1349572. Phase IIb studies of S/GSK1349572 are currently progressing as planned. ViiV Healthcare expects to begin the Phase III studies by the end of 2010. S/GSK1349572 was jointly discovered by Shionogi & Co., Ltd. and GlaxoSmithKline, and is being developed by ViiV Healthcare and Shionogi & Co., Ltd.


Highlighted Data on SELZENTRY


Several retrospective analyses in both treatment experienced and naive patients were presented evaluating additional approaches for determining tropism and virologic response to maraviroc, including the following:



-- A genotypic analysis of 704 pre-treatment samples from patients in the MERIT study who received maraviroc and had a known virologic outcome using population-based sequencing of the V3 loop, which identified 11R residue as a marker of CXCR4 use.



-- An analysis of data from the MERIT study using population-based sequencing of the V3 loop, in which approximately 8 percent of patients screened as R5 by the original Trofile™ assay were classified as X4 by V3 sequencing and 193/283 (68 percent) classified as R5 by both the enhanced sensitivity Trofile and population-based V3 sequencing had week 48 virologic response (

Study Reveals New Options For People With PKU

For people with the genetic condition known as phenylketonuria (PKU), diet is a constant struggle. They can eat virtually no protein, and instead get their daily dose of this key macronutrient by drinking a bitter-tasting formula of amino acids. Yet drink it they must; deviating from this strict dietary regimen puts them at risk of developing permanent neurological damage.


In the near future, fortunately, a better option may become available.


In April, a team of University of Wisconsin-Madison researchers will publish the second of two key papers showing that a unique protein derived from whey known as glycomacropeptide, or GMP is safe for people with PKU to eat. GMP is the first known natural protein that is safe for this group, and these findings are poised to revolutionize the PKU diet. Already, Cambrooke Foods, a Massachusetts company that specializes in the manufacture of medical foods, is in the process of developing GMP-fortified snack foods for commercial sale.


"It's so important to individuals on the PKU diet to have new options, to have their diet liberalized. It's a quality-of-life issue," says Denise Ney, a professor of nutritional sciences who led the two studies. "Adolescents have an especially difficult time [staying on the diet], but it's so critical that they do."


People with PKU are born without the enzyme responsible for breaking down phenylalanine, one of the 20 major amino acids that form the proteins we eat in everyday foods. While small amounts of phenylalanine are essential for PKU patients, excess amounts stay in their bodies indefinitely and interfere with brain function. Those who go off-diet often suffer from concentration problems and depression. Some even sustain permanent brain damage. The GMP protein isolated from whey, on the other hand, is the only known dietary protein that contains only trace amounts of phenylalanine; absolutely pure GMP, in fact, is completely phenylalanine-free.


The first GMP human feeding trial was published in February in the Journal of Inherited Metabolic Disorders. In it, Ney and her team describe the experience of an individual with PKU who volunteered to consume an all-GMP diet for 10 weeks. As the paper explains, not only did the subject enjoy the GMP-fortified snack bar, pudding and sports beverage that supplied most of his daily protein, but the amount of phenylalanine in his blood actually starting going down after he ate these items for a couple of weeks.


"And because the subject enjoyed the GMP foods, he was more inclined to eat them throughout the day, which helps keep the body's protein metabolism running efficiently all day long," says Ney. "When he went back to the amino acid formula, he went back to drinking it all in one sitting."


Ney's new study, published in the April issue of the American Journal of Clinical Nutrition and appearing online on Feb. 25, describes an 11-person trial of shorter duration involving PKU patients receiving care from UW-Madison's Waisman Center who agreed to spend six days at the University Hospital's Clinical and Translational Research Core. In the study, subjects adhered to the amino acid formula diet for four days, and then switched to the GMP diet for the following four. (Subjects spent the first two days of the study at home.) In the end, no adverse health problems were found, and 10 of 11 subjects claimed to prefer the GMP diet, making the bottom line of this study the same as the first that GMP is safe and acceptable.















In this shorter study, variations were seen among individual subjects, but the overall blood phenylalanine levels measured after meals were comparable in the two diets. Additionally, the GMP diet improved protein metabolism compared to the amino acid formula.


Members of the PKU community have been eagerly monitoring the progress of this research project for nearly a decade, since UW-Madison food engineer Mark Etzel published a key paper describing how to isolate GMP from whey. A few years ago, when things got to the point of starting human feeding trials, the researchers discovered they already had a long list of eager volunteers, including Matt Cortright of Wausau, Wisconsin, who developed seizures and other problems after abandoning the amino acid formula for a few years during early adulthood.


"The main reason I helped out with this study was so that newer generations won't have to go through the things I have. It makes me happy to see how far the studies have come since I was younger, and the choices future generations will have," writes Cortright, now 32, in a letter to Ney. "I just hope that I will also have the opportunity to use these [GMP food] products [in my own daily life] as well."


University of Wisconsin-Madison

500 Lincoln Dr., 27 Bascom Hall

Madison

WI 53706

United States

wisc

ATS Medical Provides Update On Clinical Progress Of ATS 3f Enable Aortic Bioprosthesis

ATS Medical Inc.
(Nasdaq: ATSI), manufacturer and marketer of state-of-the-art cardiac
surgery products and services, announced that a total of 47 patients
have now undergone aortic valve replacement with its sutureless ATS 3f
Enable(TM) Aortic Bioprosthesis at seven investigative sites in Europe
within both the feasibility and pivotal clinical trial phases. Currently,
eight patients have surpassed the two year implant duration.


The ATS 3f Enable Aortic Bioprosthesis is designed to eliminate the
traditional suturing required to replace a patient's diseased aortic heart
valve. If suturing can be eliminated from the procedure, surgeons can
potentially reduce procedure time and offer less invasive options for the
treatment of aortic valve disease. In addition, the elimination of suturing
offers the potential to significantly improve valve related hemodynamics by
allowing the surgeon to provide a replacement valve of a size larger than
what is traditionally possible with conventionally sutured heart valves.



The most recent phase of the clinical trial was designed to evaluate
the effectiveness of the ATS 3f Enable Aortic Bioprostheses "sutureless"
solution with respect to hemodynamics, avoiding peri-valvular leakage, and
valve migration post surgery. After more than 25 consecutive procedures
within the pivotal trial phase utilizing an updated pivotal trial protocol,
the ENABLE 'sutureless' solution has provided excellent clinical outcomes
for peri-valvular leak comparable to conventional surgery. It has been
further established that valve migration has not been a risk with the
ENABLE heart valve.



Prof. Thierry P. Carrel of the University Hospital of Bern, Switzerland
stated, "We are very encouraged by our ATS 3f Enable heart valve
experience. The unique sutureless implantation feature of the ENABLE valve
provides several important clinical benefits for our patients. Notably,
because the valve requires no sutures to implant we are able to put in a
larger valve than would otherwise be possible using a conventionally
sutured heart valve. As a result, the hemodynamic performance observed is
truly outstanding. And unlike with sutureless percutaneous valves, there
has been no trade off or compromise in clinical performance. Specifically,
we have not observed any peri-valvular leaks or migration with the ENABLE
prosthesis. Prof. Friedrich S. Eckstein, also of the University Hospital of
Bern, added, "The ENABLE sutureless implant procedure is remarkably simple.
Because we are able to eliminate the suturing and much of the time that
normally accompanies aortic valve replacement, we have been able to provide
more of our patients a less invasive procedure using smaller incisions
without compromising clinical outcome."



ATS Medical Inc. President and CEO, Michael Dale said, "We are very
pleased with the results from our updated pivotal protocol. The potential
benefits of a sutureless aortic heart valve are many, but up until the
introduction of the ENABLE heart valve, 'sutureless' designs could not
claim equality with conventional surgery outcomes. This was particularly
true with regard to peri-valvular leakage. For less invasive aortic valve
surgery to move forward as a standard of care, clinical outcomes must be at
least equivalent to conventional surgical technique. We believe these
results for ENABLE demonstrate this is possible. Our intellectual property
in this area is comprehensive and we believe our design is practical and
with this milestone we look forward to expanding our enrollment in this
exciting clinical trial."
















Prof. Sven Martens, MD, PhD, of Johann Wolfgang Goethe University
Hospital in Frankfurt, Germany said, "The ATS 3f Enable Aortic
Bioprosthesis has been chosen by us because of the excellent hemodynamics,
especially in patients with a small aortic annulus. The early results are
very promising and while more time is needed, we believe that for these
patients, this device may truly advance the standard of care for aortic
valve surgery."



The ATS 3f Enable Aortic Bioprosthesis is the second product stemming
from the ATS 3f(R) Aortic Bioprosthesis platform. Utilizing the same valve
leaflet design and materials, the company has been able to preserve
excellent product performance and durability. ATS has now expanded into the
sutureless implant procedure and will utilize these base products and
technologies to further advance the standard of heart valve repair and
replacement. ATS' strategy has been to develop and provide an excellent
Aortic Bioprosthesis, to utilize this platform to improve standard aortic
valve replacement surgery through sutureless products and procedures, and
then to provide products and procedures to allow for minimally invasive
heart valve repair and replacement in a safe and effective manner. The
company will proceed with an expanded clinical evaluation at a select
number of international sites as we proceed through the regulatory process
for US IDE and International CE Mark approvals.



About ATS Medical



ATS Medical, Inc. provides innovative products and services focused on
cardiac surgery. The company, global in scope, is headquartered in
Minneapolis, Minnesota. More than 140,000 ATS Open Pivot(R) Heart Valves,
which utilize a unique pivot design resulting in exceptional performance
and low risk profile, have been implanted in patients worldwide. The ATS
3f(R) brand encompasses multiple tissue heart valve product offerings at
varying steps from market introductions to clinical trials to development
projects that incorporate less invasive valve replacement technology. ATS
Medical's focus on serving the cardiac surgery community is further
strengthened by offerings that include ATS Simulus(R) annuloplasty products
for heart valve repair, ATS CryoMaze(TM) surgical ablation products, and
RTI-Cardiovascular for allograft tissue services. The ATS Medical web site
is atsmedical.



Safe Harbor



This Press Release contains forward-looking statements that may include
statements regarding intent, belief or current expectations of the Company
and its management. Actual results could differ materially from those
projected in the forward looking statements as a result of a number of
important factors, including the results of clinical trials, the timing of
regulatory approvals, the integration of 3f Therapeutics and the surgical
cryoablation business of CryoCath Technologies, Inc., regulatory actions,
competition, pricing pressures, supplier actions and management of growth.
For a discussion of these and other risks and uncertainties that could
affect the Company's activities and results, please refer to the Company's
filings with the Securities and Exchange Commission, including its Form
10-K for the year ended December 31, 2006 and its most recent quarterly
report on Form 10-Q.


ATS Medical Inc.

atsmedical

Diphtheria Agent Targets Malignant Cells

Scott & White's Cancer Research Institute (CRI) is conducting a clinical trial that targets malignant T-cell lymphoma, a type of blood cancer.



Lymphoma, which affects the white blood cells that normally protect against illness, is categorized either as B-cell or T-cell. About 85% of lymphomas are of B-cell origin, and 15% of T-cell origin. T-cell lymphomas are primarily chronic, but they do not respond well to chemotherapy.



Therefore, says Arthur E. Frankel, M.D., director of the Cancer Research Institute and director of Scott & White's Division of hematology/oncology, the need exists to find new agents that can selectively target and kill the malignant T-cells. The research agent under study at Scott & White contains diphtheria targeting malignant T-cells.



"This new targeted protein agent is designed to eliminate tumor cells resistant to chemotherapy," said Dr. Frankel. "The short course of treatment may improve quality of life if successful."



To date, 10 people have enrolled in the clinical trial. Scott & White's CRI will enroll up to 40 subjects to participate in this clinical trial to determine the safest doses for treatment of T-cell lymphoma. Eligible subjects for the study must have failed previous treatment options.



T-cell malignant diseases include MF/Sezary Syndrome, T-cell LGL, PTCL, T-cell CLL, T-cell NHL, angioimmunoblastic T-cell lymphoma, T-cell anaplastic large cell lymphoma, nasal extranodal T-cell lymphoma, enteropathy-type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and hepatosplenic T-cell lymphoma.

In The Modern Post-PSA Era, Prostate Cancer Surgery May Not Be Necessary For Some Patients

Investigators at Memorial Sloan-Kettering Cancer Center (MSKCC), along with collaborating teams at the Cleveland Clinic and the University of Michigan, have completed the first large- scale, multi-institutional study of prostate cancer death after standard treatment to remove the prostate since PSA screening has become widely used as a method to screen for the disease.


In the study, published online in the Journal of Clinical Oncology, researchers found that in a group of 12,677 men who had radical prostatectomies between 1987 and 2005, the fifteen-year mortality rate that could be directly linked to prostate cancer was only 12 percent, even though many of the patients' cancers had aggressive features. Comparatively, the rate of non- cancer-related death in this group was 38 percent. A small fraction, 4 percent, of patients treated surgically within the past ten years had a 5 percent or greater risk of dying of prostate cancer within 15 years. It is not clear at this time whether the outcomes may be related to the effectiveness of surgery and any secondary therapy, or to the low lethality of certain types of prostate cancers to begin with.


"The importance of this paper is that it shows a remarkably low risk of dying of prostate cancer within 15 years for treated men, and supports the concept that men with slow-growing cancers may not need immediate treatment," said senior author Peter Scardino, Chair of the Department of Surgery at MSKCC. "Further good news is that surgery was very effective in preventing death in men with aggressive cancers--defined as those with a high PSA, poorly differentiated with a Gleason grade of 8-10, or locally extensive," Dr. Scardino added.


Not all prostate cancers progress the same way. Many cancers pose little or no threat to life and health, while others grow aggressively and are resistant to treatment. The key is to determine which cancers are "favorable" or ones likely to remain relatively dormant. According to Dr. Scardino, "Currently, there are a number of tools physicians have to help determine the probable course of prostate cancer, but more accurate ones are needed."


Dr. Scardino and colleagues have formulated and pioneered the use of validated statistical models, or nomograms, that help predict the natural progression of prostate cancer and how it will respond to treatment. These nomograms help tailor treatment for men according to the specific characteristics of their cancer. The prostate cancer nomograms are currently the most widely used, disease-specific prediction tool in oncology.


In addition to the nomogram, physicians may use PSA testing, Gleason grade, MRI scans, and multiple biopsies to determine which cancers are likely to be favorable and which are not. While there are tools and models available now to help predict survival, Dr. Scardino and his fellow authors encourage future research to pinpoint better markers specifically associated with the biology of lethal prostate cancer.















"In the future, what we'd like is to be able to do a molecular or genetic analysis of prostate tumor cells to see if they have the capacity to spread, so that we can ask, does your tumor have that capacity? If not, it would be safe to watch," said Dr. Scardino.


As part of the study, 12,677 patients treated with radical prostatectomy between 1987 and 2005 were tracked. Of these patients, 6,398 underwent radical prostatectomy for localized prostate cancer at either MSKCC or Baylor College of Medicine, with 809 (13%) receiving neoadjuvant androgen-deprivation therapy for an average of 3.2 months. External validation of the nomogram was performed on 4,103 patients treated at Cleveland Clinic and 2,176 patients treated at University of Michigan during the same period.


Prostate biopsy specimens were reviewed by pathologists at each institution before surgery. In general, patients were followed for disease recurrence post operatively with regular PSA tests and clinical exams at three to six month intervals for the first five years, and then annually. The year of surgery was also a consideration, as methods and effectiveness have changed over the years.
While prostate cancer death rates have been dropping over the past decade, according to the American Cancer Society, it is estimated that there were 186,320 new cases of prostate cancer in the United States in 2008 and 28,660 deaths from the disease.


Researchers from the Cleveland Clinic, University of Michigan, and Baylor College of Medicine contributed to this study. The work was supported by SPORE grants awarded to MSKCC and the University of Michigan by the National Cancer Institute and by the David Koch Foundation and the Prostate Cancer Foundation.


Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of care worldwide.

RAD001 Phase II Trial Results Positive In Patients With Advanced Gastric Cancer After Failure Of One Or More Prior Treatments

Data released show RAD001 (also known as everolimus; proposed brand name Afinitor(R)) halted tumor growth in 55% of patients with advanced gastric cancer, a condition for which there are limited treatment options. In addition, 45% of patients in the study demonstrated some tumor shrinkage(1).


The data will be presented at the American Society of Clinical Oncology's 2009 Gastrointestinal Cancers Symposium on January 15.


The open label, single arm, multi-center Phase II study of 54 patients conducted in Japan, is designed to assess the efficacy and safety of RAD001 in patients with advanced gastric cancer whose disease progressed despite prior treatment. Patients enrolled in the trial were heavily pre-treated. All trial participants were from Japan and of Asian descent (1).


"There are very limited treatment options for patients who progressed despite the standard treatment for this aggressive cancer," said Atsushi Ohtsu, MD, PhD, Director, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan. "The results from this study demonstrate that RAD001 has the potential to provide an effective new option for these patients."


A global Phase III clinical trial program to evaluate the efficacy and safety of RAD001 monotherapy in approximately 500 advanced gastric cancer patients will begin enrollment this year.


"Most advanced gastric cancer patients eventually stop responding to current therapies, demonstrating a considerable need for new treatment options," said Alessandro Riva, MD, Executive Vice President & Global Head of Development, Novartis Oncology. "Early data show RAD001 may benefit these patients and provides the rationale for additional studies. Novartis is committed to further exploring the potential of RAD001 for this hard to treat cancer, as well as studying its role in treating other tumor types."


Gastric cancer, commonly referred to as stomach cancer, was diagnosed in 21,500 Americans in 2008 and claimed the lives of more than 10,000 in the same time period(2). This cancer is highly prevalent among people of Asian descent, with more than half of all new cases occurring in East Asia(3). It is believed that the incidence is high among this population due in part to Helicobacter pylori infection and a diet high in smoked, salted or pickled foods. Among ethnicities in the US, Asians and Pacific Islanders have the highest mortality rates(4).


Study details


The proof-of-concept, Phase II study is designed to assess the efficacy and safety of RAD001 (10 mg) daily in patients with advanced gastric cancer (inoperable, recurrent or metastatic gastric cancer) whose disease progressed despite prior treatment. The primary endpoint of the study is to assess disease control rate (DCR). Secondary endpoints included assessment of objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), and to describe the safety profile of RAD001.















The average duration of therapy was 57 days. There was a DCR (complete response/partial response/stable disease) of 55% at eight weeks (95% Confidence Interval: 40.4 - 68.4%). Of the 53 patients evaluated for the study's primary endpoint, 29 patients (55%) had stable disease, 22 (41%) had progressive disease and 2 (4%) had an unknown response. The ORR was zero. The median PFS was 83 days (95% Confidence Interval: 50 - 91 days), with 29.6% of patients estimated to still be progression-free at four months. Median overall survival was not attained at the time of evaluation.


The most commonly reported adverse events (all grades; >10% patients) in the study included, stomatitis, anorexia, fatigue, rash, nausea, edema peripheral, thrombocytopenia, diarrhea, pruritus, anemia, dysgeusia, vomiting, pyrexia, pneumonitis, constipation and insomnia. Serious adverse events (grade 3 or 4; >3% of patients) included anemia, hyponatremia, raised liver function, fatigue, stomatitis, anorexia, hyperglycemia, hypophosphatemia, ileus and lymphopenia.


About RAD001


RAD001, an oral once-daily inhibitor of mTOR, is an investigational drug being studied in multiple tumor types. In cancer cells, RAD001 provides daily inhibition of mTOR, a protein that acts as a central regulator of tumor cell division, cell metabolism and blood vessel growth.


RAD001 is being studied in multiple cancer types including advanced kidney, breast and neuroendocrine tumors and lymphoma. Currently, RAD001 is under regulatory review in the US and Europe for the treatment of advanced renal cell carcinoma.


The safety and efficacy profile of RAD001 has not yet been established in oncology and there is no guarantee that RAD001 will become commercially available for oncology indications. The active ingredient in RAD001 is everolimus, which is available in different dosage strengths under the trade name Certican(R) for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003. Certican is not approved in the US.


Disclaimer


The foregoing release contains forward-looking statements that can be identified by terminology such as "promising," "will," "potential," "may," "committed," "exploring," "believed," "estimated," "anticipated," or similar expressions, or by express or implied discussions regarding potential regulatory filings or marketing approvals for RAD001 or regarding potential future revenues from RAD001. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with RAD001 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that RAD001 will be approved for sale for any oncology indication in any market. Nor can there be any guarantee that RAD001 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding RAD001 could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.


About Novartis Pharmaceuticals Corporation


Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, GI and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.


Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG which provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs, innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 97,000 full-time associates and operate in over 140 countries around the world. For more information, please visit novartis.


References


(1) Ohtsu, A et al. Multicenter phase II study of RAD001 for previously treated metastatic gastric cancer. Presented at the American Society of Clinical Oncology's 2009 Gastrointestinal Cancers Symposium, January 15, 2008.


(2) American Cancer Society. Detailed Guide: Stomach Cancer. Available at : cancer/docroot/CRI/content


(3) Ohtsu, A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol 2008; 43:256-264.


(4) American Cancer Society. Overview: Stomach Cancer.


Novartis Pharmaceuticals Corporation

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European Commission Grants Full Approval Of HIV Protease Inhibitor, Tipranavir (Aptivus&reg;)

Ingelheim/Germany, 28 April 2008 - Boehringer Ingelheim announced that the European Commission has given the full marketing authorisation to its HIV protease inhibitor (PI), Aptivus® (tipranavir). The Commission has fully approved Aptivus ® for the suppression of HIV in highly treatment experienced patients who have developed resistance to other protease inhibitors.


Resistance to HIV therapies is a considerable problem, with an increasing number of people developing strains of HIV that are resistant to protease inhibitors. For example, in one study in the UK 27% of treatment-experienced patients demonstrated resistance against protease inhibitors 1 and in Spain, 43% of patients treated for more than eight years carry more than five protease resistance mutations. 2


Dr Andreas Barner, Member of the Board of Boehringer Ingelheim and responsible for Research, Development and Medicine said: "We welcome this decision by the EU Commission to grant full marketing authorisation for Aptivus®. This full approval demonstrates the confidence that the authorities have in the benefit of Aptivus® for patients with resistant virus."


Aptivus®, the first non-peptidic protease inhibitor, shows good antiviral activity against viruses that have shown decreased susceptibility to other currently marketed PIs.3


The decision to grant full marketing authorisation was taken on the evidence of two large multicentre pivotal trials (RESIST I and II) demonstrating Aptivus® superiority across several efficacy measures to a group of comparator PIs boosted with ritonavir. Treatment response rates* over 156 weeks were almost three times higher in the Aptivus® arm compared to the comparator arm (20.9% vs. 7.5%) and were markedly higher for those patients who also started a new class of HIV therapy (here: Enfurvitide). 3


With over 1,400 participants 4 the RESIST trials are one of the largest studies ever of treatment-experienced patients. The data demonstrate that Aptivus® enables treatment-experienced patients to achieve and sustain undetectable viral loads, one of the most important goals of therapy. This efficacy, alongside the acceptable safety profile of Aptivus®, as seen in more than 20.000 patient years of use of Aptivus®, prompted European authorities to remove the 'exceptional circumstances' restriction on the marketing authorisation, previously granted in 2005.


Holger P., a patient from Frankfurt, Germany, who has been treated with nearly all the 22 currently available HIV drugs, said: "This full approval is good news for treatment experienced patients like me. It gives us the confidence that our therapies have passed the rigorous tests demanded of them. With drugs like tipranavir available to us, we can, regardless of our treatment experience, aim for an undetectable viral load."















Attaining an undetectable viral load has been shown in several studies to prolong survival and reduce the risk of AIDS or death by more than 80% in people with HIV that have become resistant to multiple therapies and classes of therapies.5,6


About Aptivus®


Aptivus® is a non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.


Based on available clinical and in vitro data, Aptivus® is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors.


Currently, phase II and III studies in paediatric and other populations are fully enrolled and ongoing.


The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking Aptivus® are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred. Elevated transaminase, cholesterol and triglycerides were more frequent in the Aptivus®/r arm than in the ritonavir boosted comparator group but only in a minority of cases treatment discontinuation was necessary.


Aptivus® boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.


Aptivus®-containing HAART regimens have been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH) in some highly treatment-experienced patients. Caution should be used when prescribing Aptivus®/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.


Aptivus ® does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.


Apart from the EU, Aptivus® received U.S. marketing authorization by the FDA and was launched there in June 2005. On Oct 4th, 2007, the FDA granted traditional approval for Aptivus®. Additional marketing authorizations from different countries have been received or are expected.


About Boehringer Ingelheim HIV Clinical Trials


Boehringer Ingelheim is actively conducting clinical trial programs to further evaluate Aptivus® and the non-nucleoside-reverse transcriptase inhibitor (NNRTI) Viramune® for the treatment of HIV-1 infection.


POTENT is a trial comparing the efficacy and safety of Aptivus® (tipranavir) versus darunavir, both with ritonavir as part of combination antiretroviral therapy. POTENT will include 800 treatment-experienced patients in 15 countries. The primary endpoint is time to virologic failure, with a secondary endpoint of virologic response at 48 weeks of treatment.


SPRING study will be one of the largest racially and gender diverse international studies of highly treatment-experienced HIV-1 infected patients. The trial will examine the safety, efficacy and pharmacokinetics of Aptivus® (tipranavir) in a racially diverse group of 200 female and 200 male treatment-experienced patients across eight countries in three continents.


RESIST I, II two large-scale clinical studies on tipranavir involving more than 1,400 patients (RESIST-I and RESIST-II) formed the foundation of the marketing authorization approval by the EMEA. The RESIST clinical trial program is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with multiple combinations of antiretroviral drug regimens.


The Viramune® clinical trial program includes the ArTEN trial, which aims to compare the efficacy and safety of Viramune dosed once or twice daily versus atazanavir boosted with ritonavir in HIV-positive antiretroviral-na??ve patients.


About Boehringer Ingelheim


Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from Aptivus® (tipranavir), Viramune® (nevirapine) is a product of original research done at Boehringer Ingelheim. Viramune® was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.


This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.


References:


1. Pillay D, Green H on behalf of the UK Collaborative Group on HIV Drug Resistance and the UK Register of HIV Seroconverters, 12th International HIV Drug Resistance Workshop


2. Rodes B, Garcia F, Gutierrez C, Martinez-Picado J, Aguilera A, Saumoy M, Vallejo A, Domingo P, Dalmau D, Riera M, Blanco JL, Pedreira J, de Mendoza C, Perez-Elias MJ, Vidal F, Leal M, Soriano V. Prevalence of cross-resistance genotypes in treatment-experienced patients. Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. B12107.


3. Hicks et al. Tipranavir/r (TPV/r) maintains long term virological suppression - Three year follow-up of RESIST; 11th annual European AIDS Conference (EACS); 24-27 October 2007, Madrid, Spain. Abstract number P4.3/70.


4. Hicks CB, Cahn P, Cooper DA, et al on behalf of RESIST investigator group. Durable efficacy of tripanavir-ritonavir in combination with an optimised background regimen of antiretrovital drugs for treatment experienced HIV-1 infected patients at 48 weeks. Lancet 2006;368:466-475


5. Zaccarelli M, Tozzi V, Forbici F, et al. Achieving undetectable HIV viral load after genotypic resistance test dramatically decreases HIV progression and survival even in more advanced patients. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 93.


6. Bracciale L, Colafigli M, Di Giambenedetto S, et al. Reaching undetectable HIV RNA levels is an independent predictor of AIDS-free survival in patients with 3-class resistant HIV-1. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 90.


Boehringer Ingelheim

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