Amgen and Johnson & Johnson have received a jolt after US regulators demanded that the firms toughen up the labelling on their big-selling anaemia treatments.

The US Food and Drug Administration says that new safety and dosage information needs to be put on the labels of Amgen’s erythropoiesis-stimulating agents Aranesp (darbepoetin alfa) and Epogen (epoetin alfa) and Johnson & Johnson's Procrit (also epoetin alfa).

The new boxed warnings advise physicians to monitor red blood cell levels and to adjust the ESA dose to maintain the lowest haemoglobin level needed to avoid the need for blood transfusions and physicians and patients are being warned to carefully weigh the risks of these products against transfusion risks.

Increased risk of death

The FDA says it has acted because recently completed studies “describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses.” In other studies, more rapid tumour growth occurred in patients with head and neck cancer who received these higher doses.

The new labelling also needs to note that in studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopaedic surgery.

Amgen responded by noting that it is changing the label and is notifying healthcare professionals of the move. Roger Perlmutter, executive vice president of R&D, said the firm is committed to “providing timely and appropriate communications to physicians and patients whenever we become aware of new safety information that could affect clinical practice."

However he also noted that "the boxed warning includes information from several investigational studies that were previously communicated to the medical community," adding that “the vast majority of oncologists and nephrologists do not appear to be maintaining haemaglobin levels above 12 g/dL in approved indications."

All of the three drugs mentioned by the FDA are currently approved to treat anaemia associated with chronic kidney disease and chemotherapy, while Epogen and Procrit are also approved to treat patients scheduled for major surgery to reduce their chances of needing blood transfusions. In addition, the two are also indicated to treat anaemia associated with zidovudine therapy in HIV patients.

The FDA’s concern is such that its Oncologic Drugs Advisory Committee plans to hold a meeting on May 10 to evaluate the recent studies and decide whether additional labelling might be needed and the news of the agency’s renewed interest in ESAs has hurt Amgen’s shares.

Fourth-quarter sales of Aranesp surged 27% to $1.11 billion, while Epogen, whose growth has been pegged back by conversion of patients to Aranesp, rose 6% to $661 million. The black box warnings are unlikely to help those sales improve and getting approvals in other indications may now prove more difficult. Recently, Amgen shares slipped after preliminary data from an independent study looking at Aranesp for an unapproved use in patients with head and neck cancer undergoing radiotherapy showed the drug fared no better than placebo.