Epoetin beta

Erythropoietin is a hormone which stimulates the production of red blood cells. A recombinant form, epoetin alfa, has been available for several years. Australian clinicians now have the option of prescribing recombinant epoetin beta, a form which has been available in Europe since 1990.

Like epoetin alfa, epoetin beta is genetically engineered using Chinese hamster ovary cells. Its protein sequence is indistinguishable from natural erythropoietin.

Following injection there is a dose-related response in the bone marrow. The dose is adjusted according to the packed cell volume or haemoglobin concentration. In the anaemia of chronic renal failure the regimen consists of a correction phase and then a maintenance phase.

Epoetin beta can be given by subcutaneous injection or by intravenous injection over two minutes. The bioavailability of the subcutaneous injection is less than half that of intravenous doses, but the half-life is longer (8-22 hours vs 4-12 hours) and lower doses can be used. In the correction phase of renal anaemia epoetin is given three times a week, but the subcutaneous injection can be given daily. It may be possible during the maintenance phase to give a subcutaneous dose once every two weeks.

There have been several studies of epoetin beta for the anaemia of chronic renal failure. Most patients reach their target haematocrit after 12 weeks of treatment. Patients can successfully maintain their haematocrit with self-administered injections.¹(This study used a pen injector which is not available in Australia.) While most of the patients will be on dialysis, epoetin beta can be used if patients with chronic renal insufficiency develop a symptomatic anaemia before starting dialysis.

Anaemia is common in patients with cancer particularly if they have been subjected to chemotherapy. In a placebo-controlled study of 349 patients with haematological malignancies, injecting epoetin beta subcutaneously three times a week for 16 weeks significantly reduced the need for blood transfusions. The patients' quality of life improved as their haemoglobin increased.²Another study of 241 patients with lymphoproliferative malignancies found that a once-weekly injection was as effective as three times a week.³

In addition to treating chemotherapy-induced anaemia in non-myeloid malignancies, epoetin beta, like epoetin alfa, is approved for increasing the yield of autologous blood donations, for example when people donate their own blood before undergoing surgery. Epoetin beta is also approved for preventing anaemia in premature babies.

As the packed cell volume increases the patient's blood pressure may rise. The risk of thrombosis may increase, particularly if there is a rise in platelet production. There is also a possibility that epoetin could stimulate tumour growth.

Iron studies and electrolytes should be regularly checked. Most patients will require iron supplements. Neutralising anti-erythropoietin antibodies can develop. If this results in red cell aplasia treatment must stop.

The pain of subcutaneous injections of epoetin beta has been compared with that of epoetin alfa. In a small study patients were injected with both products for four weeks. Pain scores were significantly lower with epoetin beta.⁴Another study compared epoetin beta with buffered formulations of epoetin alfa, and saline, by giving 60 patients four simultaneous injections. Epoetin beta was more acceptable than epoetin alfa and some patients felt it was no more painful than the saline injection.⁵

When indicated, epoetin beta will help to ameliorate the anaemia in most patients, but it may not improve long- term outcomes, at least in malignant disease. During a median follow-up of 27-28 months in 343 patients with lymphoproliferative malignancies, the median survival was 18 months with placebo and 17 months with epoetin beta.6

Manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.