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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: Robert K. who wrote (6796)	7/25/1998 10:00:00 PM
From: aknahow	Respond to of 17367

All sepsis is not Meningococcemia, but as you state, Meningococcemia is sepsis. Great proof of concept. Other types of sepsis are still killers, so if Neuprex helps with one type of sepsis how many think it will not be used for other types. While it would be nice to see an early halt, I think the trial will go through Dec. but December is not that far away.

To: Robert K. who wrote (6796)	7/25/1998 10:16:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Bayers sepsis trial failed. Bayer is aware of Xoma's work in this area. Bayer would be a logical partner, and I think Merck would also. Merck has a vaccine for Meningococcemia as well as an interest in anti infective drugs. Previous Release Return to Index Next Release BAYER AG ANNOUNCES ESTABLISHMENT OF INTERNATIONAL SEPSIS FORUM :: This press release is transmitted on behalf of Bayer AG Brussels, Belgium, March 18 - Bayer AG announced today plans to establish an International Sepsis Forum dedicated to improving the awareness, understanding and clinical management of sepsis and septic shock. Claiming in excess of 200,000 lives each year in the United States alone, septic shock is one of the most common causes of death in hospital intensive care units worldwide. The establishment of the International Sepsis Forum (ISF) was announced at the 17th Annual International Symposium of Intensive Care and Emergency Medicine (ISICEM) by Professor Jean-Louis Vincent, MD, PhD, Chairman of the ISICEM and Clinical Director of Intensive Care at the Erasme University Hospital, Free University in Brussels. The ISICEM is being held March 18-21 at the Congress Centre in Brussels. The ISF will be supported by an unrestricted educational grant from Bayer AG. Directed by an independent Steering Committee made up of international experts on sepsis and its treatment, the ISF will sponsor lectures and symposia and issue a series of publications on sepsis and septic shock management. Additionally, the ISF will develop educational materials to keep physicians and other medical personnel up-to-date on the latest developments relating to the number one infectious killer in intensive care units. ''The establishment of this Forum is precisely what we have needed for some time in order to more successfully coordinate the worldwide battle against sepsis,'' said Professor Vincent, who serves as a member of the ISF Steering Committee. Sepsis is the medical term for a life-threatening, systemic reaction to infection, and its symptoms include elevated temperature, heart rate and respiration. Unless successfully treated, sepsis progresses to septic shock, organ failure, and death. The incidence of sepsis and septic shock has risen substantially in the last decade due to an increase in the number of susceptible individuals including surgical patients, the elderly, AIDS patients, organ transplant recipients, and other immune compromised patients. Although newer antibiotics and intensive care technologies have been helpful in the management of septic shock, death rates have changed little in the past 20 years. Those that survive, generally require about two weeks of intensive-care hospitalisation, at a cost of more than US dollars 5 billion per year in the United States alone. ''The ISF represents a commitment to saving lives,'' said Gordon Bernard, MD, Chairman of the ISF Steering Committee. ''The primary goal of the Forum is to achieve international consensus on key scientific research and clinical issues in sepsis treatment, and to develop practical treatment guidelines for those treating sepsis patients.'' Dr. Bernard, an internationally renowned expert on sepsis, is Professor of Medicine and Director, Medical Intensive Care Unit, Vanderbilt University School of Medicine, in Nashville, Tennessee. ''We expect that the ISF will provide resources and support for new ideas that will help shape the future of the treatment and management of sepsis and septic shock,'' said Professor Dr. Dieter Maruhn, Head of Anti-Infectives Product Development at Bayer. Professor Maruhn also noted that Bayer was among the companies at the forefront of sepsis research and has a promising septic shock treatment in clinical trials. If that treatment is found to be successful, there will be ethical, socio-economic, and treatment issues related to its use which a group such as the ISF will be uniquely situated to deal with. ''We will need guidance on these delicate issues and we believe that the ISF, led by Dr. Bernard and other leaders in the field, is the body to provide that guidance to Bayer,'' Maruhn said. Bayer is an international research-based company with major businesses in life sciences, chemicals and imaging technology. With 142,000 employees worldwide, Bayer recorded a global earnings of DM 2.7 billion after tax on sales of DM 48.6 billion in 1996. Advisory to editors: UNS does not warrant or make any representations regarding the correctness, accuracy or reliability of the contents of the press release. Under no circumstances shall UNS be liable for damages resulting from the use of information contained in the press release. All facts should be independently checked. Media contact details for this story Return to the top of the page c 1997 Two-Ten Communications Limited

To: Robert K. who wrote (6796)	7/25/1998 10:28:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Bob, think RobertS would care about Bayer's estimate of the hospital cost in the U.S. for survivors of present ineffective treatments? Naw, his objective was something else, but just in case one does not read the prior post with care, here it is: "Those that survive, generally require about two weeks of intensive-care hospitalisation, at a cost of more than US dollars 5 billion per year in the United States alone." Gee, think there will be a market for Neuprex if it works?

To: Robert K. who wrote (6796)	7/25/1998 10:41:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Potential for quick diagnosis: Cell Biochemistry Martinsried Risk Assessment for Sepsis and Shock in Intensive Care Unit (ICU) Patients G.Valet, W.Kellermann1) 1) Abt.An„sthesiologie, Krankenhaus-Schwabing der TUM, Munich, Germany SMDC in Research and Medicine Intensive care patients are in life threatening conditions when affected by sepsis or non infectious shock. Granulocytes represent a major defense barrier against these affections. They phagocytose microorganisms or tissue breakdown products, but they also release enzymes or pharmacologically active mediators. In this way they can represent a danger for the organism if their potent functionalities escape inhibitory control mechanisms. It is clinically of utmost importance to recognize the danger of sepsis or shock as early as possible. Unfortunately, this is not readily possible by the determination of humoral biochemical markers in the vascular or other body compartments. The concept of this work was to determine cell function parameters of granulo- and monocytes at a molecular level to obtain predictive (prognostic) indicators of imminent danger to patients. Our earlier flow cytometric work (1,2) using bacterial phagocytosis (6,7), ADB intracellular pH and esterase (1,2) measurements as well as acridine orange as indicator of cellular and bacterial RNA and DNA(7) had shown for the first time that the prediction of imminent danger of sepsis and non infectious shock in intensive care (IC) patients was already possible two to three days in advance to the appearence of clinical symptoms (2). These findings provide a significantly increased therapeutic lead time for the clinician. Although conceptually promising, the use of bacteria in a phagocytosis assay is comparatively complicated e.g. in automatically operated flow cytometers. The concept was therefore to facilitate the practical approach to cell function assays. This was achieved by: 1. the use of humoral stimulators like e.g. cytokines and 2. the development of the very sensitive oxidative burst indicator dye (8,10,11,14) dihydrorhodamine123 (DHR) and of the highly specific rhodamine110 substrates for the determination of protease activity (12,13,17-22,24) in vital cells. These developments have substantially simplified the determination of blood cell functions in infection, sepsis or non infectious shock. Flow cytometric data of such measurements are typically collected as list mode files. They are then evaluated in a standardized and automated way by the CLASSIF1 (4,6) multiparameter data classification program. The analysis of the entire data set by the CLASSIF1 program system reveiled that the incubation of ex-vivo leukocyte preparations: - alone (ex-vivo) - with physiological stimulators such as: suboptimal concentrations of FMLP (formyl-methionyl-leucyl-phenylalanyl bacterial peptide), TNF-alpha (tumor necrosis factor-alpha), FMLP+TNF-alpha and - with phorbol ester (PMA, phorbol-myristate-acetate) as maximum stimulator provides a sufficient amount of predictive information (6) for the early risk determination in septically admitted IC patients e.g. already on the day of admission, similarly as the cytometric determination of proteolytic enzyme activities like: - cysteine proteinases or - serine proteinases The exhaustive optimization of the classification process for the same group of septically admitted IC patients showed (6) that the most discriminant predictive information was contained in only two assays which were the FMLP and TNF-alpha stimulated oxidative burst (DHR123) assays rather than in the unstimulated ex-vivo assay or in the maximum (PMA), in the combined (FMLP+TNF-alpha) stimulation assays or in the protease activity assays. As a practical consequence of the CLASSIF1 multiparameter data analysis, only two out of the seven performed assays were really required for survival prediction in this group of septically admitted IC patients (6). Conclusion: 1. functional parameters of granulocytes and monocytes contain predictive information for disease outcome in septically admitted IC patients already on the day of admission 2. Optimization of multiparameter data classification by CLASSIF1 analysis shows that the most discriminant information is contained in two (FMLP/TNF-alpha) physiologically stimulated oxidative burst (DHR123) assays out of seven cytometrically determined oxidative burst and protease activity assays on vital peripheral blood leukocytes On-line classification of sepsis and shock cases (in preparation) Cell Biochemistry For problems or comments, please contact: G.Valet E-mail: valet@biochem.mpg.de, Max-Planck-Institut fr Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany, Tel: +49/89/8578-2518, -2525, Fax: +49/89/8578-2563, INTERNET address: biochem.mpg.de Last Update: Jun.29, 1998

To: Robert K. who wrote (6796)	7/25/1998 10:58:00 PM
From: aknahow	Read Replies (2) \| Respond to of 17367

So if one finds a cure and can save a good portion of the $5 billion in hospital cost for survivors would one spend $600,000,000 on treatment? Works out to about $1,000 per patient. This is an old report and deals with E5 not Neuprex when XOMA is discussed. Decided not to spend the $900 until the report is revised. <g> Free Summary Page View the description or purchase the publication THE U.S. MARKET FOR SEPSIS THERAPEUTICS AND PREVENTIVE AGENTS Market Size and Growth The first products to prevent or treat sepsis or septic shock are expected in 1998, and the U.S. market could reach $300 million that year in current manufacturers' dollars. By the year 2000, the U.S. sepsis product market may achieve sales of $600 million. Definition The presentation of systemic inflammatory response syndrome (SIRS) ranges from sepsis, to septic shock, to multiple organ failure. When SIRS is the result of a confirmed infectious process, it is termed sepsis. Sepsis is defined as a systemic response to infection by microbes or their products. Product Segments Scores of agents have been suggested for possible prevention or treatment of sepsis. Many are untested, a few have been tried clinically, and a few have been tried clinically and failed. Market Share If Xoma/Pfizer's E5 (edobacomab), a murine monoclonal antibody antisepsis product, enters the U.S. market in 1998 as projected, it would be the greatest contributor to the sepsis product market, which in that year could reach $300 million. Costs It is estimated that the cost of treating sepsis and septic shock averages $16,000 per patient in the United States. Hospital charges range from $5 billion to $10 billion annually. Issues and Trends Resistance to available anti-infectives is increasing at an alarming rate. Overuse and careless use of anti-infectives have resulted in a situation in which resistance is increasing more rapidly than efforts to contain it. The Patient In 1992, 637,597 people in the United States were hospitalized with sepsis. This represents a 7% increase from 1991, when 596,213 patients were diagnosed with the disease. Approximately 45% of patients with sepsis progress to septic shock, and approximately 100,000 Americans die from septic shock annually. Industry Structure Less than 20 companies in 1995 state that they are actively pursuing the development of drugs to prevent or treat sepsis or septic shock. Given the unpopularity of the word "sepsis" on Wall Street, it is believed that many more companies are working on compounds that could be used for this indication, but are being developed for others. Company Profiles Alpha-Beta Technology, Inc. Biogen, Inc. Genentech, Inc. Immunex Corp. T Cell Sciences, Inc. Xoma Corp. Go Home \| Search \| Request Research \| Clients Only \| Send Message \| Keep Me Posted

To: Robert K. who wrote (6796)	7/25/1998 11:18:00 PM
From: aknahow	Respond to of 17367

More sepsis! Neuprex anyone? Bacterial and fungal sepsis-related deaths after liver transplantation M. Ahmed, MD, D. Mirza, FRCS, D. Mayer, FRCS, J. Buckels, FRCS, P. McMaster, FRCS and J. Pirenne, MD, Liver Unit, Birmingham, UK and UZ Gasthuisberg, Leuven, Belgium. Results of liver transplantation (LTx) have dramatically improved over the last decade, but sepsis remains a major cause of mortality. We searched to identify demographics, incidence, timing, and risk factors for deaths directly related to either bacterial sepsis or fungal sepsis after LTx. Methods: Prospectively collected data of consecutive adult (>16 yo) LTx done between 1982-1996 were reviewed. Deaths due to sepsis were analyzed. Septic deaths secondary to Hepatic Artery Thrombosis (HAT), Multiple Organ Failure (MOF), and Primary Non Function (PNF) were not included. Mann-Whitney, Kruskal-Wallis, and Fisher exact tests were used -p< 0.05 was considered as significant (S). Results: 898 adults were transplanted during the study period and the 1, 5, and 10 year patient survival was 77%, 70%, and 63%, respectively. 256 patients (28.5%) died during follow-up (up to 14 years). Mortality due to primary bacterial sepsis and fungal sepsis was 8.5% and 7.8%, respectively. Other causes of deaths included MOF (19.5%), HAT (3.5%), PNF (2.3%), chronic rejection (2%), tumor recurrence (11%), and miscellaneous: hemorrhage, cardiac, disease recurrence, accident etc...(45.4%). Median time to death was 59.5 days (1-1789) after bacterial sepsis and 42.5 days (9-802) after fungal sepsis. Deaths due to: Bacterial Sepsis; n=22 Fungal Sepsis; n=20 Control; n=642 Age 52.5 47.8 49 Days on ventilation 2 4* 1 Poor nutritional status 3/22 (13.6%) 4/20 (20%)* 51/642 (8%) Retransplant 6/22 (27%)* 6/20 (30%)* 44/642 (6.8%) Fulminant liver failure 4/22 (18%) 6/20 (30%)* 84/642 (13%) Blood transfusion-units 8.5 (0-54)* 14 (1-62)* 5 (0-58) Day3 creatinine (um/L) 218 (64-737)* 174 (72-550)* 101 (45-536) significant, compared with survivors. *p=0.07 Conclusions: 1) Primary bacterial and fungal sepsis (unrelated to HAT, MOF, and PNF) represent an important cause of death after LTx (16.3%); 2) Risk factors for both bacterial and fungal sepsis include reTx, intraoperative blood transfusion, and postTx renal dysfunction; and 3) Deaths to fungal sepsis were also associated with poor nutritional status preTx, Tx for fulminant liver failure, and prolonged ventilatory support postTx. To decrease sepsis-related mortality after LTx, more aggressive anti-bacterial and anti-fungal prophylaxis should be adopted in these high-risk recipient categories.

To: Robert K. who wrote (6796)	7/26/1998 12:17:00 AM
From: aknahow	Read Replies (1) \| Respond to of 17367

And for a complete discussion of sepsis: medscape.com

To: Robert K. who wrote (6796)	7/26/1998 12:52:00 AM
From: aknahow	Read Replies (1) \| Respond to of 17367

And like Biostock1 used to say, treatment begins at once even before the exact bateria is identified. "Treatment: Hospitalization is necessary to achieve treatment goals. Intravenous antibiotic therapy should be initiated as soon as the diagnosis is suspected. The therapy is not delayed while determining the causative organism. Sometimes more than one type of antibiotic is given while results of the blood cultures are pending. Antibiotics can then be changed when the culture results are available and the causative organism is known. The source of the infection should be identified if possible, which may mean further diagnostic testing. Sources such as infected intravenous lines or surgical drains can be removed, and sources such as abscesses can be surgically drained. Supportive therapy with oxygen and intravenous fluid and management of complications is important for a good outcome. "