Gleevec Resistance

Novartis's (NYSE: NVS) Gleevec (imatinib mesylate) was touted as a "magic bullet" for the treatment of chronic myelogenous leukemia (CML). But there is a big difference between magic and medicine. Medicine has limitations. As often occurs with medicines, patients with CML can become resistant to treatment with Gleevec. Approximately 8,000 new cases of CML are diagnosed each year.

Though we began discussing Gleevec resistance in May of last year, many investors are expressing surprise by recent reports of Gleevec failures. This article will review what Gleevec can and cannot accomplish in the treatment of CML, and look at alternatives for Gleevec resistant patients.

At the December 2001 American Society of Hematology (ASH) meeting, presentations demonstrated that complete cytogenetic response rates reported with Gleevec treatment are consistently and significantly higher than those historically documented with other CML therapies over a broad range of clinical circumstances. Elimination of CML cells that harbor the characteristic chromosomal rearrangement seen in the majority of cases of the disease is the ultimate molecular goal of CML treatment. Gleevec studies in CML continue to demonstrate favorable data, including longer term and refined, robust data.

However, the greatest CCR rates are seen with the treatment of newly diagnosed, CML therapy naïve, patients in the chronic phase of CML. A plenary session at ASH demonstrated that Gleevec resistance occurred most commonly in the blast crisis phase of CML. Blast crisis is a phase of CML when cancer cells have not only the hallmark chromosomal translocation associated with CML, but also many other genetic changes that lead to clinical difficulties for patients. In patients with blast crisis, resistance to Gleevec occurs in approximately 60-70% of the patients, whereas resistance is very rare in those in the early, chronic phase.

As with treatment of many types of cancer, these observations point out the need for early identification of CML. For those not fortunate enough to have their disease discovered early, the authors of several well-conceived studies have recommend investigation of combination therapy with Gleevec and other agents as a means to overcoming some cases of resistance. Therefore, Gleevec will continue to be used for patients with all stages of CML, although treatment of blast crisis will be more aggressive.

Gleevec is being tested in combination with standard chemotherapy. In addition, preclinical data was presented at the American Association of Cancer Research meeting last week for Gleevec in combination with various farnesyl transferase inhibitors (Johnson & Johnson's [NYSE: JNJ] Zarnestra is in phase II trials) and in combination with Genta's (NASDAQ: GNTA) Genasense.

Gleevec rescue studies in CML are intense and ongoing. More data will be presented in May at the American Society of Clinical Oncology meeting. These data by no means negate the value of Gleevec; rather they highlight the opportunities for increased use in combination with other anti-cancer agents.

BTECH NEWS
by Leon Henderson, M.D.
Bennett Weintraub, Ph.D.
Christopher Martin
www.btechnews.com
April 18, 2002

RETURN TO INDEX

BTECH NEWS, published by Btech Investor, Inc., highlights selected events in the life sciences sector that the Btech Investor team believes are particularly relevant to biotechnology investors. The Btech Investor team combines scientific, clinical, and business experience to perform comprehensive analysis of the biotechnology industry and to identify future industry leaders.

BTECH INVESTOR REPORTS

The Btech Investor Reports provide in-depth analysis of the biotechnology industry. Recent companies profiled include Vertex, EntreMed, Élan, IDEC Pharmaceuticals, Myriad Genetics, and Abgenix. Recent sector reports include nucleic acid therapeutics, Alzheimer disease, inhaled insulin, recombinant proteins, gene therapy, monoclonal antibodies, neurodegenerative diseases, stem cells, trends in oncology, genomics based drug discovery, and biotech trends.

BTECH DISCLAIMER

Btech Investor aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of Btech Investor may hold positions in some or all of the stocks discussed in this report.

© Copyright 2002, Btech Investor, Inc.

Additional DISCLAIMER
Information transmitted via BioPortfolio has been provided by the original publishers Btech Investor Incorprated ("Btech"). It is not guaranteed as to completeness or accuracy by BioPortfolio, the Btech publishers, or any person. Such Information is neither an offer to sell nor a solicitation to buy the securities of any company. Opinions expressed are subject to change without notice. The Information and views provided by Btech are prepared by Btech employees and in no way reflect the views or efforts of BioPortfolio Limited., any of BioPortfolio's employees or officers. BioPortfolio, and BioPortfolio's employees and officers, as well as Btech’s employees and officers, in no way accept responsibility for any of the Btech content published on www.bioportfolio.com/. 

While all reasonable care has been taken to ensure that the Information contained herein is presented in good faith, and is not untrue or misleading at the time of publication, BioPortfolio, and Btech make no representation as to its accuracy or completeness and it should not be relied upon as such. The Information is supplied on the condition that the reader or any other person receiving the Information will make his or her own determination as to its suitability for any purpose prior to any use of the Information. From time to time, BioPortfolio and any officers or employees of BioPortfolio, as well as Btech, and any officers or employees of Btech, may, to the extent permitted by law, have a position or otherwise be interested in any transactions, in any investments (including derivatives) directly or indirectly the subject of this report. Also BioPortfolio and Btech may, from time to time solicit business from any company mentioned in this report. This report is provided solely for the information of viewers of BioPortfolio and/or viewers and subscribers of Btech and BioPortfolio information services, who are expected to make their own investment decisions without reliance on this report. Neither BioPortfolio nor any officer or employee of BioPortfolio, nor Btech, or any officer or employee of Btech, accepts any liability whatsoever for any direct, indirect, special or consequential damages or loss arising from any use of this report or their contents. This report may not be reproduced, distributed or published by any recipient for any purpose without the prior express consent of the publishers. Nothing contained herein shall be construed as conferring by implication, estoppel or otherwise any license or right under any patent, trademark or copyright of BioPortfolio, Btech or any third party. 

The value of the investment(s) to which this report relates and their income yield(s) may go up or down. The investment(s) referred to in this report may not be suitable for private investors: if you are in any doubt you should seek advice from your investment advisor. Changes in rates of currency exchange may have an adverse effect on the value, price or income of investments. Statements as to past performance of any investment are not a guide to future performance. The levels and bases of taxation can change, and if you are in doubt you should seek independent professional advice. In some cases it may be difficult for you to sell or realize your investment or to obtain reliable information about its value or the extent of the risks to which you are exposed. 

THIS INFORMATION IS PROVIDED "AS IS" AND NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED OF ACCURACY, MERCHANTIBILITY FITNESS FOR A PARTICULAR PURPOSE OR OF ANY OTHER NATURE ARE MADE WITH RESPECT TO THIS INFORMATION OR TO ANY EXPRESSED VIEWS PRESENTED IN THIS INFORMATION.