TKT, Genzyme: Wettbewerb um Fabry-Krankheit - 500 Beiträge pro Seite

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Gegen die bislang medikamentös nicht zu behandelnde Fabry-Krankheit gibt es einen hoffnungsvollen Medikamentenkandidaten: Ein Enzym hat sich bei jüngsten Tests an Patienten als wirkungsvoll erwiesen. 69% der behandelten Personen wiesen dabei signifikante Verbesserungen auf.

Die Fabry-Krankheit geht auf einen genetischen Defekt zurück. Sie führt zu einem erhöhten Anteil von Fetten im Blut, was zu Leberversagen und Herzanfällen führen kann. Durchschnittlich ein Mensch auf 40.000 ist von dieser Krankheit betroffen.

Da mit Genzyme und Transkaryotic Therapies (TKT) zwei Unternehmen ein Medikament auf der Basis des gleichen Enzyms auf den Markt bringen wollen, sind Auseinandersetzungen vorprogrammiert. TKT befindet sich mit Replagal im Zulassungsprozess, Genzym sucht für Fabrazyme die Vermarktungserlaubnis für Europa und die USA.

Wenig überraschend ist, dass beide Companys seit vergangenem Jahr in einem Rechtsstreit liegen. Genzyme hat TKT vorgeworfen, die eigenen Patente auf das heilende Enzym zu verletzen, was seitens der Beklagten zurück gewiesen wird. Der Rechtsstreit ist weiter vor Gericht anhängig. Hierin zeigt sich die Tendenz, patentrechtliche Fragen als strategisches Instrument im Wettbewerb um Marktanteile zu verwenden.

TKT und Genzym spielen im Biotech-Segment in zwei verschiedenen Ligen: Genzym bringt mit einer Marktkapitalisierung von über 11 Mrd. Dollar deutlich mehr auf die Waage als TKT, das mit rund 740 Mio. Dollar bewertet wird. TKT ist eine kleinere Beteiligung im Portfolio von BB Biotech.

[peter.wedemeier1]

Thursday July 5, 2001 09:42 AM
Company Press Release

SOURCE:Genzyme General


Positive Phase 3 Results for Genzyme General``s Fabrazyme(TM) Published in New England Journal of Medicine

CAMBRIDGE, Mass., July 5 /PRNewswire/ -- Genzyme General (Nasdaq: GENZ) reported that a paper published in today`s New England Journal of Medicine shows that Fabrazyme(TM) (agalsidase beta) can clear the lipid globotriaosylceramide (GL-3) from the plasma and the blood vessels of the kidneys, heart and skin in patients with Fabry disease. The results come from Genzyme`s Phase 3 trial of Fabrazyme, an investigational enzyme replacement therapy for patients with Fabry disease.

The results published today show that Fabrazyme addresses the major pathology underlying Fabry disease: the accumulation of GL-3 in the blood vessels of the major affected organs. In patients with Fabry disease, this buildup often leads to reduced blood flow and organ failure, particularly in the kidneys, heart, and brain. The results were achieved in a double-blind, placebo-controlled, multicenter trial that enrolled 58 patients at eight medical centers in Europe and the United States. It was the largest clinical trial ever conducted for Fabry disease or any lysosomal storage disorder.

The pivotal trial`s primary end point was the clearance of GL-3 from the microvascular endothelial cells in the kidney. After 20 weeks of treatment, 20 of 29 patients (69 percent) who received Fabrazyme had achieved complete or almost complete clearance, as compared with none in the placebo group. In addition, Fabrazyme was able to bring about clearance of GL-3 to near-normal levels from the capillaries of the heart, kidney and skin, and a reduction of GL-3 in kidney tissue and urine. Previously elevated plasma GL-3 levels were consistently reduced to undetectable levels in the Fabrazyme-treated group, and plasma levels correlated with the clearance of GL-3 from tissues. A statistically significant decrease from baseline in pain was noted for both treatment groups.

All patients continued therapy in the open-label extension trial. Complete vascular clearance to near normal levels was achieved in 98 percent of patients who underwent a repeat kidney biopsy six months into the extension trial, demonstrating that the clearance achieved in the first five months was maintained, and that the placebo patients could achieve the same response when crossed over to Fabrazyme treatment. Similarly, complete or near complete vascular clearance was seen in 96 percent of the skin biopsies, and 75 percent of the heart biopsies. Of note, kidney function remained essentially normal in these patients during the year of follow-up.

"The results published today offer tremendous hope for meeting the needs of patients with Fabry disease," said Robert J. Desnick, M.D., Ph.D, of Mount Sinai School of Medicine, an author of the study and an eminent leader in the development of therapies for lysosomal storage disorders. "We have shown it is possible to reliably achieve total or near-total clearance of GL-3 through a precise dose of Fabrazyme. This achievement is a validation of our meticulous approach to developing the best possible protein and determining the optimal dose for patients, and the culmination of the work of the many investigators in this trial."

In an editorial accompanying the paper, William A. Gahl, M.D., Ph.D. of the National Institutes of Health, said that "an intimate knowledge" of Fabry disease enabled the study`s investigators to select "an appropriate outcome measure and to perform serial renal biopsies for proof of efficacy. Thus, Fabry`s disease now joins Gaucher`s disease ... as a lysosomal storage disorder that is treatable by enzyme replacement."

The vascular clearance of GL-3 observed in the Phase 3 trial was achieved with a dose of 1 milligram of Fabrazyme per kilogram of patient body weight administered every other week - a dosing level chosen as a result of a prior Phase 1/2 trial comparing the effectiveness of three different doses (0.3 mg/kg 1.0 mg/kg 3.0 mg/kg) over three months. In the earlier trial, a dose of 0.3 mg/kg was shown to reduce GL-3 but not clear it consistently, resulting, for example, in a 75 percent reduction of GL-3 from baseline. The 1 mg/kg dose cleared GL-3 from the plasma and from the blood vessels of the major organs.

Fabry disease is caused by a deficiency of the enzyme alpha-galactosidase. This deficiency results in the body`s inability to break down certain glycolipids -- primarily GL-3 -- which then accumulate in the lining of the blood vessels within the kidney, heart, skin and other organs. Although some accumulation also occurs in other cells, it is the progressive accumulation of these lipids in the blood vessels that results in symptoms such as kidney failure, stroke, cardiovascular disease, severe pain and numbness. These organ complications lead to death on average around age 40 unless patients undergo dialysis or a renal transplant.

These phase 3 data, along with results from the earlier phase 1/2 study, were submitted to regulatory agencies last summer for marketing approval in the U.S. and Europe. Fabrazyme has been recommended for marketing approval in the European Union, and it has been sold in France since late last year. A biologics license application is under regulatory review in the United States.

As Genzyme has presented at two scientific meetings, the Fabrazyme protein is fully sialylated, which reduces non-specific removal by the liver, and it has appropriate levels of mannose-6-phosphate to ensure uptake into the proper compartment (lysosomes) of the target cells.

To create Fabrazyme, Genzyme drew on its extensive experience in the glycobiology of enzyme replacement therapy, including more than a decade of work with Ceradase(R) (alglucerase for injection) and Cerezyme(R) (imiglucerase for injection) for Type 1 Gaucher disease. Genzyme`s broad- based commitment to lysosomal storage disorders also includes programs to develop treatments for MPS 1, Niemann-Pick disease, and Pompe disease.

No additional safety concerns were noted in the Phase 3 trial or its extension compared to the previous Phase 1/2 trial. Many of the patients developed antibodies, but most of these demonstrated a downward trend in antibody titers over the period of observation. No effect of antibodies on the clearance of GL-3 was observed. The most common reported infusion-related events included chills and fever, which were noted at some point in about half of the patients, but did not preclude continued treatment.

Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General has four therapeutic products on the market and a strong pipeline of therapeutic products in development focused primarily on the treatment of genetic diseases and other chronic, debilitating disorders with well-defined patient populations. Genzyme General is a division of the biotechnology company Genzyme Corporation.

This press release contains forward-looking statements based on management`s current expectations, including statements about: the potential receipt of marketing approval for Fabrazyme and expectations concerning the potential to meet the needs of Fabry patients. Actual results may materially differ due to numerous factors, including: the timing and content of decisions made by the European Commission, the FDA and other regulatory authorities with respect to submissions made by Genzyme and its competitors for therapies for Fabry disease the final results of a Phase 4 trial the efficacy of products the long-term efficacy of Fabrazyme and the risks and uncertainties described in reports filed by Genzyme Corporation with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme`s 2000 Annual Report on Form 10-K. Genzyme General Division common stock is a series of common stock of Genzyme Corporation. Therefore, holders of Genzyme General Division common stock are subject to all of the risks and uncertainties described in the aforementioned reports.

Genzyme(R), Ceredase(R) and Cerezyme(R) are registered trademarks and Fabrazyme(TM) is a trademark of Genzyme Corporation. All rights are reserved.