Another day, and another story about the ups and downs of US biotech bellwether Amgen, and in particular its top-selling anaemia drug Aranesp (darbepoetin alfa).

In the latest instalment the European Medicines Agency’s Committee for Medicinal Products for Human Use has proposed changing the labelling for Aranesp and other erythropoiesis-stimulating agents (ESAs) to include a warning that using it to boost haemoglobin levels to more than 12 grams/dl should be avoided because this raises the risk of “unexplained excess mortality”.

The CHMP is suggesting that treatment with ESAs should aim to bring haemoglobin into the 10-12 g/dl range, but no higher, and points out that there is no benefit in terms of overall survival or reducing the risk of tumour progression when ESAs are used in anaemia associated with cancer. A final verdict on the label change is not expected until early 2008, and Amgen said it would be in discussion with the EMEA on the final wording.

All companies marketing ESAs, including Johnson & Johnson and Roche, have been through the wringer of late. In March, the US Food and Drug Administration (FDA) changed the labelling of ESAs to warn of an increased risk of death, heart attacks and strokes if haemoglobin levels are pushed above 12g/dl.

Meanwhile, in July the Medicare programme in the US decided it would restrict reimbursement of ESAs used in patients with chemotherapy-associated anaemia if haemoglobin levels topped 10g/dl, although there is pressure on Medicare to reconsider. An intensive lobbying effort by the company was followed earlier this month with a resolution being passed in the Senate seeking a reassessment of the decision.

Amgen has arguably been hit the hardest as ESAs account for such a large proportion (almost half) of its turnover. For example, after its launch in 2001 to treat anaemia associated with chronic renal failure, Aranesp saw sales advance swiftly and hit a peak of $4.1 billion in 2006. But sales slumped around 10% in the first half of this year on the safety concerns and restrictions on reimbursement, and a period of cost-cutting has ensued, with over 2,000 workers to be laid off as part of an effort to trim costs by $1-$1.3 billion in 2008.

Stock barely moved on the news

Amgen’s stock barely moved on the CHMP news, reflecting the conservative use of ESAs in Europe compared to the USA, and suggesting that investors have already factored in the impact on Amgen’s revenues in 2007. One analyst has already suggested that Aranesp could lose 40% of its turnover this year.

But with deliberations on the safety of ESAs now ongoing on both sides of the Atlantic, the biotech has been fighting back, and earlier this week presented new clinical data supporting the safety of Aranesp in the management of cancer patients and finding no evidence to suggest a negative impact on overall survival or progression-free survival between patients receiving chemotherapy with Aranesp and those that did not receive the drug.