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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/448577/2012

EMEA/H/C/000760

EPAR summary for the public

Silapo

epoetin zeta

This document is a summary of the European Public Assessment Report (EPAR) for Silapo. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Silapo.

What is Silapo?

Silapo is a solution for injection. It is available in prefilled syringes containing between 1,000 and 40,000 international units (IU) of the active substance epoetin zeta.

Silapo is a 'biosimilar' medicine. This means that Silapo is similar to a biological medicine (the 'reference medicine') that is already authorised in the European Union (EU), and contains a similar active substance to the reference medicine. The reference medicine for Silapo is Eprex/Erypo, which contains epoetin alfa. For more information on biosimilar medicines, see the question-and-answer document here.

What is Silapo used for?

Silapo is used in the following situations:

•    to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems;

•    to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions;

•    to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery.

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The medicine can only be obtained with a prescription.

How is Silapo used?

Treatment with Silapo must be started under the supervision of doctors who have experience in the management of patients with the conditions that the medicine is used for.

For patients with kidney problems, Silapo can be injected into a vein or under the skin. For patients receiving chemotherapy, it must be injected under the skin, and for patients about to undergo surgery, it must be injected into a vein over at least one to five minutes. The dose, the frequency of injection and how long Silapo is used for depend on why it is being used and the patient's bodyweight, and are adjusted according to the patient's response. For patients with chronic renal failure or receiving chemotherapy, haemoglobin levels should remain within the recommended range (between 10 and 12 grams per decilitre in adults and between 9.5 and 11 g/dl in children). Haemoglobin is the protein in red blood cells that carries oxygen around the body. The lowest dose that provides adequate control of symptoms should be used.

The iron levels of all patients should be checked before treatment to make sure that they are not too low, and iron supplements should be used throughout treatment. Silapo can be injected under the skin by the patient or their carer if they have been trained appropriately. For full details, see the package leaflet.

How does Silapo work?

A hormone called erythropoietin stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. In these cases, erythropoietin is used to replace the missing hormone or to increase red blood cell counts. Erythropoietin is also used before surgery to increase the number of red blood cells to help patients produce more blood for self-donation.

The active substance in Silapo, epoetin zeta, is a copy of human erythropoietin and works in exactly the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin zeta.

How has Silapo been studied?

Silapo was studied to show that it is comparable with the reference medicine, Eprex/Erypo, in experimental models and in humans.

Silapo, injected into a vein, was compared with the reference medicine in two main studies involving 922 patients who had anaemia associated with chronic renal failure requiring haemodialysis (a technique for removing waste products from the blood). The first study compared the effects of Silapo with those of Eprex/Erypo in correcting red blood cell counts in 609 patients over 24 weeks. The second study compared the effects of Silapo with those of Eprex/Erypo in maintaining red blood cell counts in 313 patients. All of the patients in the second study had been receiving treatment with Eprex/Erypo for at least three months before they were either switched to Silapo or remained on Eprex/Erypo for 12 weeks. After that, the two groups switched to receiving the other medicine for a further 12 weeks. In both studies, the main measures of effectiveness were the levels of haemoglobin during treatment, as well as the dose of epoetin received.

Silapo

The company also presented the results of two studies looking at the effects of Silapo injected under the skin: one involved 261 cancer patients receiving chemotherapy, and the other compared Silapo with Eprex/Erypo in 462 patients with anaemia caused by kidney problems.

What benefit has Silapo shown during the studies?

Silapo was as effective as Eprex/Erypo in correcting and maintaining red blood cell counts. In the correction study, haemoglobin levels were around 11.6 g/dl during the last four weeks of the study, having risen from around 8.0 g/dl before treatment. In the study of patients already being treated with an epoetin, haemoglobin levels were maintained at around 11.4 g/dl when the patients were receiving Silapo and when they were receiving Eprex/Erypo. In both studies, the dose of epoetin received was similar with both medicines.

Silapo was also effective when it was injected under the skin. The study in patients receiving chemotherapy showed that Silapo brought about similar improvements in haemoglobin levels as those reported in the scientific literature for other epoetins. Silapo was also as effective as the reference medicine in patients with kidney problems.

What is the risk associated with Silapo?

As with other medicines containing an epoetin, side effects during treatment are mainly observed in patients with chronic renal failure and cancer. The most common side effects with Silapo are headache and an increase in blood pressure. A severe rise in blood pressure can sometimes be accompanied with symptoms of encephalopathy (brain problems) such as sudden stabbing migraine-like headache. For the full list of all side effects reported with Silapo, see the package leaflet.

Silapo must not be used in people who are hypersensitive (allergic) to epoetin zeta or any of the other ingredients. It must not be used in patients who have developed pure red cell aplasia (reduced or stopped red blood cell production) following treatment with any erythropoietin, patients with hypertension (high blood pressure) that is not controlled, patients about to undergo surgery who have severe cardiovascular (heart and blood vessel) problems including a recent heart attack or stroke, or patients who cannot receive medicines to prevent blood clots.

Why has Silapo been approved?

The CHMP concluded that, in accordance with EU requirements, Silapo has been shown to have a comparable quality, safety and efficacy profile to Eprex/Erypo. Therefore, the CHMP's view was that, as for Eprex/Erypo, the benefit outweighs the identified risks. The Committee recommended that Silapo be given marketing authorisation.

Other information about Silapo:

The European Commission granted a marketing authorisation valid throughout the EU for Silapo on 18 December 2007.

The full EPAR for Silapo can be found here. For more information about treatment with Silapo, read the package leaflet (also part of the EPAR).

This summary was last updated in 07-2012.

Silapo

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