Anaemia drug could endanger kidney patients - The Borneo Post - Monday, 18 February, 2002

LOS ANGELES: A small number of European kidney dialysis patients treated with Johnson &--Johnson's anaemia drug Eprex developed a rare, but potentially deadly, blood disorder, according to a study in the New England Journal of Medicine.

The New Brunswick, New Jersey based company said in December it had warned doctors in Europe and Canada of the risk of an immune response to the injected drug, which could result in pure red-cell aplasia, a condition in which the bone marrow fails to produce vital red blood cells - the opposite of the drug's intended function.

At that time, the company said it discovered 40 patients on Eprex had developed the disorder and it had revised its warning label on Eprex.

The drug, which has been around for 15 years, is marketed in the United States as Procrit.  The number of aplasia patients has since reportedly risen to 75.

In the New England Journal report, Dr. Nicole Casadevall, of the Hopital Hotel-Dieu in Paris, and colleagues observed 13 cases in which patients developed aplasia after three to 67 months of treatment with Eprex.

Eprex is a genetically engineered version of erythropoietin, a hormone that stimulates production of oxygen carrying red blood cells. Rights to the drug outside of the United States, as well as rights for US patients other than those on kidney dialysis, were licensed in 1985 to J J by Amgen Inc. which sells the drug domestically, under the brand name Epogen, in the kidney dialysis market.

J J's combined sales of Eprex and Procrit totalled about $3.8 billion last year.  Amgen's sales of Epogen and Aranesp, a recently launched longerlasting version of the drug, reached $2.2 billion.

The French researchers said that blood tests showed that antibodies to the drug can develop in anaemic patients with chronic kidney failure.  After treatment was discontinued, the antibody levels slowly decreased.

Johnson & Johnson has said in the past that the chance of developing aplasia from being treated with Eprex is less than one in 10,000.

In an accompanying editorial, Dr. H. Franklin Bunn, of Brigham and Women's Hospital in Boston, said the patients with induced aplasia had much more severe anaemia than the anaemia of kidney failure that prompted the treatment.

He said this immune response is the only serious adverse effect of the recombinant human protein that has occurred when it was administered under proper medical supervision.

Bunn said this raises the question of whether the manufacturing process for the European product has altered either the formulation or the carbohydrate structure of the hormone.

He said this is of particular concern following Amgen's recent launch of Aranesp, a version of the drug with a carbohydrate structure designed so that it stays in the body longer.

"It will be important to determine whether darbepoetin alfa (Aranesp) engenders cross-reacting antibodies," he said.

"Aranesp is a different molecule. It was studied in 6,000 people - one of the largest-ever clinical trials for a biologic," said Jeff Richardson, a spokesman for Amgen.-Reuters