Is Pure Red-Cell Aplasia Linked to All Epo Products or Just Eprex?

According to a recently published study, treatment with Johnson & Johnson's (NYSE: JNJ) Eprex can, in rare cases, lead to the nearly total shut down of red blood cell production. The study, published last week in the New England Journal of Medicine, found that European patients with chronic renal failure treated with recombinant human erythropoietin are at risk for forming neutralizing anti-erythropoietin antibodies that can result in the development of the inability to make red blood cells, a condition called pure red-cell aplasia.

French investigators identified thirteen chronic dialysis patients who developed severe transfusion-dependent anemia between 1998 and 2000 after taking recombinant human erythropoietin (epo). The diagnosis of pure red-cell aplasia was based on the characteristic appearance of the bone marrow and circulating blood. 12 of the 13 patients had been treated with epoetin-alpha (Eprex), and one with epoetin-beta, (Roche's [Swiss: ROG] NeoRecormon). Their severe anemia developed after 3 to 67 months of treatment. After discontinuing erythropoietin treatment, six patients were able to develop red cell synthetic bone marrow function on their own after being treated with immunosuppressants or a renal allograft, while three remain transfusion-dependent more than 2 years later. Four still require transfusions, but it is not yet clear if they will remain transfusion-dependent.

In all the patients studied, the red-cell aplasia was caused by an immune reaction against the therapeutic epo. The patients made antibodies that neutralized not only the drug, but also their own natural epo. Without epo in their body, they were not able to make red blood cells. Serum concentrations of the antibodies declined after manufactured epo was discontinued.

In December 2001, Johnson & Johnson warned doctors in Europe and Canada that an immune response to Eprex could result in pure red-cell aplasia. At that time, Johnson & Johnson had discovered that 40 patients on Eprex had developed pure red-cell aplasia, and it had revised its warning label on Eprex to reflect these incident cases. The total number of patients that have experienced this complication is now approximately 75. The risk of patients being treated with Eprex developing pure red-cell aplasia appears to be less than one in 10,000. Pure red-cell aplasia is the only serious adverse effect of recombinant epo administered under appropriate medical supervision.

Marketing of epo is complicated: Johnson & Johnson markets recombinant epo as Eprex in Europe and to cancer patients in the U.S. as Procrit. The drug was originally developed by Amgen (NASDAQ: AMGN), who sells it to kidney dialysis and certain other patients in the U.S. as Epogen. It is not clear whether or not pure red-cell aplasia will be an adverse effect of all of these drugs or only Eprex. Although Eprex, Procrit, and Epogen are often considered identical drugs, differences in manufacturing could be responsible for the adverse effect that has been seen mainly with Eprex so far. Further complicating the picture is the entry of Amgen's Aranesp, a longer lasting epo formulation, to the market in both Europe and the U.S.

Until investigators determine exactly what aspect of Eprex causes red-cell aplasia, there is much speculation about the role of the European manufacturing process versus the role of the carbohydrate structure of epo itself. Although the incidence of red-cell aplasia is low enough that it will probably not affect overall sales of epo, a problem with Eprex  manufacturing could significantly benefit Amgen, especially with physicians offered the new choice of using Aranesp. Further boosting the case for Amgen 's products is the fact that, in 12 years of marketing Epogen, there has been only one case of a patient developing pure red-cell aplasia.

On the other hand, if red-cell aplasia is a rare side effect of all epo based products, it could have a negative impact on Aranesp sales. Because Aranesp is longer acting due to the addition of more sugar residues (hyperglycosylation) to the epo protein, it has the potential to be more immunogenic than unmodified recombinant epo (Eprex, Procrit, and Epogen). However, this theoretical possibility has not been seen in real patients - none of the over 6,000 patients receiving Aranesp have had any indication of red-cell aplasia. However, even if Aranesp patients do not develop red-cell aplasia, the fact that this adverse effect has been demonstrated in an epo product may slow future label expansion of Aranesp into anemia of chronic diseases such as lupus, inflammatory bowel disease, or diabetes.

Although signs of red-cell aplasia and other adverse effects should be closely monitored, all indications are that Aranesp is significantly more convenient than other epo products and is being well accepted by physicians. We expect strong sales of Aranesp in both the U.S. and in Europe, with a significant boost in sales after its use in the oncology market picks up, especially after its impending registry for oncology in the United States Pharmacopeia.

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