British Biotech Batimastat clinical program revised.OXFORD, England--(BUSINESS WIRE)--Feb. 17, 1995--British Biotech announced today that one of its two clinical programs involving the injectable anti-cancer drug batimastat has been delayed, pending changes to the manufacturing process. This delay affects only the clinical trials in malignant ascites malignant ascites Excess peritoneal fluid evoked by malignancy, which causes subdiaphragmatic lymphatic obstruction–eg, of the thoracic duct and ↑ intraperitoneal fluid production Etiology Ovarian, breast, gastric, pancreatic, hepatic, colorectal CA, , a form of late stage abdominal cancer. In these studies, unexpected side effects Side effects Effects of a proposed project on other parts of the firm. have been encountered in patients receiving batimastat manufactured at the larger batch size required for Phase III trials. Studies in malignant pleural effusion Pleural Effusion Definition Pleural effusion occurs when too much fluid collects in the pleural space (the space between the two layers of the pleura). It is commonly known as "water on the lungs. , a similar late stage cancer occurring in the chest cavity, are not affected and are continuing without interruption. The oral matrix metalloproteinase inhibitor, BB-2516, is a different compound from batimastat and is unaffected by this delay. Revisions made to the manufacturing process during the course of scaling up production of batimastat for Phase III have now been shown to be associated with reduced patient tolerance. All affected supplies of the drug have been recalled and new supplies are currently being manufactured. The final step of manufacture will now be carried out exactly as in the original process. The company expects to have regulatory approval by June 1995 for re-commencement of its malignant ascites clinical program. The first trial will be a dose-rising study. Dr. Keith McCullagh, British Biotech's chief executive, commented: "This interruption is unfortunate and will prevent the company from meeting its objective of submitting a marketing application for batimastat in Europe by the end of the first quarter 1996. However, we have identified the problem as associated with a change in the final stage of the manufacturing process which has now been corrected. As a result, the delay will be limited and the potential of batimastat as a new treatment for certain types of advanced cancer remains unaffected. In that regard, we are encouraged by the opportunity for batimastat in the treatment of malignant pleural effusion where progress has been good. The company's other new drugs under development, including the two cancer drugs, BB-2516 and BB-10010, continue on track." Technical Note Clinical Experience With Batimastat In Malignant Ascites Following a successful Phase II, 40-patient study in malignant ascites, British Biotech began a 150-patient Phase III randomised Adj. 1. randomised - set up or distributed in a deliberately random way randomized irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" controlled trial controlled trial Clinical research A clinical study in which one group of participants receives an experimental drug while the other receives either a placebo or an approved–'gold standard' therapy. See Blinding, Double-blinded. of batimastat versus no drug treatment in November 1994. Malignant ascites is a serious, late stage complication of ovarian and other intra-abdominal cancers and is unresponsive to current therapy, being normally relieved by repeated drainage of ascitic as·ci·tes n. pl. ascites An abnormal accumulation of serous fluid in the abdominal cavity. [Middle English aschites, from Late Latin asc fluid. Batimastat, an inhibitor of matrix metalloproteinases (MMPs), has shown beneficial effect on the rate of fluid reaccumalation in Phase I/II and Phase II studies. In the Phase III trial, which has recently been suspended, a majority of the patients receiving batimastat reported pain and discomfort following intra-peritoneal administration of the drug. Previous experience with batimastat administered by the same route to a total of more than 85 malignant ascites patients in a variety of Phase I/II and Phase II trials had shown the drug to be well tolerated and pain and discomfort following dosing to be minimal. The incidence of side effects encountered in the Phase III malignant ascites trial has therefore been significantly different from previous experience with batimastat in this condition. This has led to a detailed analysis of the formulation used in the Phase III trial. Manufacturing Process New chemical entities under development by British Biotech are manufactured for large scale clinical trials and eventual commercial use by external contractors using British Biotech's proprietary routes of synthesis to closely defined specifications approved by regulatory agencies. A number of changes to the batimastat production process have been made to improve the efficiency of manufacturing as production is increased in scale. All material used in the clinical trials has been made to a closely defined specification using Good Manufacturing Practice Good Manufacturing Practice or GMP (also referred to as 'cGMP' or 'current Good Manufacturing Practice') is a term that is recognized worldwide for the control and management of manufacturing and quality control testing of foods and pharmaceutical products. guidelines. Despite meeting current ICH See Intel Hub Architecture. guidelines, batimastat made by the larger scale process has been significantly more irritant to the peritoneum peritoneum (pĕrətənē`əm), multilayered membrane which lines the abdominal cavity, and supports and covers the organs within it. The part of the membrane that lines the abdominal cavity is called the parietal peritoneum. than material produced by the earlier smaller scale process. After extensive investigation the problem has been identified with changes made to the final step in the manufacturing process. Alterations have now been made to the large scale manufacturing process and to the product specification which will avoid this problem by reverting to the previously successful method of production. Fresh clinical supplies of batimastat made by this revised process are now being manufactured. Batimastat program in malignant pleural effusion British Biotech is also investigating the potential for batimastat in the treatment of malignant pleural effusion, a similar condition to malignant ascites but occurring in the chest cavity. This is a significantly more common condition than malignant ascites, being a relatively frequent complication of primary and secondary lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. . A UK Phase I/II study of batimastat administered by direct injection into the chest cavity is nearing completion in 24 pleural effusion patients. This trial is being supplied with batimastat unaffected by the manufacturing problem described above. Tolerability of batimastat in the pleural effusion patients has been good and the clinical program is continuing. Full results of this study are being presented at the American Society of Clinical Oncology American Society of Clinical Oncology, or ASCO, is an organization that represents all clinical oncologists. Every year, ASCO holds a large symposium where physicians and researchers meet to convey and discuss research and ideas. (ASCO ASCO American Society of Clinical Oncology ASCO Association of Schools and Colleges of Optometry (since 1941; Rockville, Maryland) ASCO Australian Standard Classification of Occupations ASCO Automatic Switch Company ) in May in Los Angeles. Increased emphasis will be given to this indication for batimastat and multicenter dose ranging efficacy studies will be conducted in parallel in Europe and the USA during 1995. Other MMP MMP Matrix Metalloproteinase (enzymes related to tissue healing/remodeling and cancer cell metastasis) MMP Mixed Member Proportional (New Zealand electoral system) MMP Multi-man Publishing Inhibitors under development Batimastat is the first matrix metalloproteinase inhibitor world-wide undergoing clinical trials in cancer patients. The manufacturing problem outlined above is unrelated to the biochemical action of batimastat as an inhibitor of matrix metalloproteinases. In addition, British Biotech has a number of other matrix metalloproteinase inhibitors under development including BB-2516, an oral anti-cancer drug, currently in Phase I volunteer studies and a second oral agent with different activities in preclinical development for arthritis. None of these development programs are affected by the delay to the batimastat ascites Ascites Definition Ascites is an abnormal accumulation of fluid in the abdomen. Description Rapidly developing (acute) ascites can occur as a complication of trauma, perforated ulcer, appendicitis, or inflammation of the colon or other trials announced today. Background British Biotech plc, founded in 1986, combines approaches in molecular biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller and synthetic chemistry to develop new therapeutic agents primarily for the treatment of cancer. In addition, the company is pursuing research in inflammatory, vascular and viral diseases. The company has recently established a new subsidiary, Neures, to investigate the role of metalloproteinase inhibitors in neuro-inflammatory diseases. British Biotech, based in Oxford, England is listed on the London Stock Exchange London Stock Exchange London marketplace for securities. It was formed in 1773 by a group of stockbrokers who had been doing business informally in local coffeehouses. and quoted on NASDAQ NASDAQ in full National Association of Securities Dealers Automated Quotations U.S. market for over-the-counter securities. Established in 1971 by the National Association of Securities Dealers (NASD), NASDAQ is an automated quotation system that reports on under the symbol BBIOY. A US subsidiary, British Biotech Inc., was established in Annapolis, Maryland, in December 1993. CONTACT: British Biotech plc James Noble, Finance Director Katie Arber, Public Relations Manager 011-44-865-748747 or Peter McCann, President 410/266-7909 or G.A. Kraut kraut n. 1. Sauerkraut. 2. often Kraut Offensive Slang Used as a disparaging term for a German. [German; see sauerkraut.] Noun 1. Company Gerard Coffey 212/696-5600 |
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