Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Mircera (Roche)
prefilled syringes containing 30, 50, 75, 100, 120, 150, 200 or 250 microgram in 0.3 mL
Approved indication: anaemia associated with chronic kidney disease
Australian Medicines Handbook section 7.5.1

Erythropoietin is a hormone produced by the kidneys which stimulates red blood cell production. Patients with chronic kidney disease may produce less erythropoietin than normal and develop anaemia (Aust Prescr 2009;32:129-31). Recombinant forms of the hormone (darbepoetin alfa, epoetin alfa, epoetin beta) have been available for several years and have been shown to benefit these patients.

Methoxy polyethylene glycol-epoetin beta is also a recombinant product. It has been chemically modified and has different activity to erythropoietin at the receptor level it associates with the receptor more slowly, but dissociates faster. It has a much longer half-life than erythropoietin and does not need to be given as often. After subcutaneous administration, maximum serum concentrations are reached after 72 hours. The elimination half-life is 139 hours after a subcutaneous injection and 134 hours after an intravenous injection. Haemodialysis has no effect on serum concentrations of this drug.

There have been several open-label comparative trials of methoxy polyethylene glycol-epoetin beta for treating anaemia in chronic kidney disease. The main efficacy measure in these trials was correction or maintenance of haemoglobin concentrations. Two of these studies were in patients starting treatment for anaemia. The first was in 181 patients on dialysis. After 24 weeks of treatment, methoxy polyethylene glycol-epoetin beta (given intravenously once every two weeks) seemed to be as effective as epoetin (given three times a week). Following dose titration, 93% of patients receiving methoxy polyethylene glycol-epoetin beta and 91% of patients receiving epoetin alfa or epoetin beta had responded to treatment (haemoglobin increase of at least 10 g/L from baseline and haemoglobin target of at least 110 g/L without a blood transfusion).1 In the second trial of 324 patients not on dialysis, methoxy polyethylene glycol-epoetin beta (given subcutaneously every two weeks) was non-inferior to darbepoetin alfa (given weekly). Almost all patients (98% with methoxy polyethylene glycol-epoetin beta, 96% with darbepoetin alfa) had responded to treatment by 28 weeks.2

In four other trials, the efficacy of methoxy polyethylene glycol-epoetin beta was assessed in patients on dialysis who were either switched to methoxy polyethylene glycol-epoetin beta or remained on epoetin therapy. When given intravenously3,4 or subcutaneously5,6 once every one, two or three weeks, or once a month, methoxy polyethylene glycol-epoetin beta maintained haemoglobin levels as effectively as the original erythropoiesis-stimulating drug.

The adverse effects of methoxy polyethylene glycol-epoetin beta are similar to other erythropoiesis-stimulating drugs, and include an increase in cardiovascular and thrombotic events, and sudden death. The most commonly reported event was hypertension so methoxy polyethylene glycol-epoetin beta should not be given to patients with uncontrolled hypertension. Other common adverse events included diarrhoea, nasopharyngitis and headache. However, the frequency of these events was similar in the comparator groups.

During the trials, methoxy polyethylene glycol-epoetin beta reduced platelet count more than other erythropoiesis stimulating drugs. Thrombocytopenia (less than 100 x 109 platelets/L) occurred in 9% of patients receiving methoxy polyethylene glycol-epoetin beta compared to 6.2% of patients receiving the comparator. Gastrointestinal and urinary bleeding events were also higher with the study drug than with other epoetins. The risk may be increased with co-administration of antiplatelet drugs.

This drug should be used with caution in patients with epilepsy. Care should also be taken in patients with haemoglobinopathies or a platelet count of more than 500 x 109/L.

Pure red cell aplasia can be caused by antibodies to erythropoietin. Patients with these neutralising antibodies should not be switched to methoxy polyethylene glycol-epoetin beta. Like other erythropoiesis-stimulating drugs, methoxy polyethylene glycolepoetin beta increases the risk of death in patients with cancer and should not be used to treat their anaemia.

Methoxy polyethylene glycol-epoetin beta can be given subcutaneously or intravenously. Subcutaneous injections can be given in the abdomen, arm or thigh. The starting dose and the dosing frequency of this drug depend on whether the patient is already receiving erythropoietin or is starting treatment. The product information explains how to calculate the dose if a patient is switching from another erythropoietin. In treatment-nave patients, the recommended dose is 0.6 microgram/kg every two weeks initially. Increases in haemoglobin usually occur after 7-15 days. Haemoglobin should be monitored regularly and the dose should be adjusted to maintain a target of 100-120 g/L. Rises in haemoglobin should not be above 10 g/L in a two-week period. Once the target is reached, methoxy polyethylene glycol-epoetin beta can be given once a month. Concomitant supplementary iron is recommended for all patients with serum ferritin values below 100 microgram/L, or whose transferrin saturation is less than 20%.

Methoxy polyethylene glycol-epoetin beta seems to be as effective as other epoetins for correcting and maintaining haemoglobin concentrations in patients with renal anaemia.

However, evidence of direct clinical benefit such as reduced morbidity and mortality is limited.

Read about The Transparency Score Manufacturer provided the clinical evaluation

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

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).

References

  1. Klinger M, Arias M, Vargemezis V, Besarab A, Sulowicz W, Gerntholtz T, et al. Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomised trial. Am J Kidney Dis 2007;50:989-1000.
  2. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol 2008;3:337-47.
  3. Levin NW, Fishbane S, Canedo FV, Zeig S, Nasar GM, Moran JE, et al. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007;370:1415-21.
  4. Canaud B, Mingardi G, Braun J, Aljama P, Kerr PG, Locatelli F, et al. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study. Nephrol Dial Transplant 2008;23:3654-61.
  5. Locatelli F, Villa G, de Francisco AL, Albertazzi A, Adrogue HJ, Dougherty FC, et al. Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration. Curr Med Res Opin 2007;23:969-79.
  6. Sulowicz W, Locatelli F, Ryckelynck JP, Balla J, Csiky B, Harris K, et al. Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol 2007;2:637-46.