Retacrit is a biosimilar of Eprex/Erypo that contains epoetin zeta and is used to treat anemia. It has the same amino acid structure and glycosylation pattern as epoetin alfa. Studies found Retacrit was as effective as correcting and maintaining red blood cell counts in patients with kidney disease and chemotherapy-induced anemia as Eprex/Erypo. Common side effects include increased blood pressure and rare side effects include cerebral hemorrhage. Retacrit was approved for use in Europe in 2007 and its biosimilar application is under review by the FDA in the U.S.

1. RETACRIT (Epoetin Zeta)

2. • Retacrit (Epoetin zeta) is a derivative of the endogenous protein
erythropoietin and is a biosimilar of the rHuEPO Eprex/Erypo, which
contains epoetin alfa.
• It is made by Hospira, Inc. is a U.S.-based global pharmaceutical and
medical device company with headquarters in Lake Forest, Illinois.

3. Molecular Structure
• As a biosimilar to epoetin alfa, epoetin zeta
has the same 165-amino-acid structure and
comparable carbohydrate composition with
only minor differences in the glycosylation
pattern.
• Epoetin alfa and zeta both have 14 sialic acid
residues, and are short acting drugs with a
half-life of 6–8 hours when administered
intravenously or 19–24 hours if administered
subcutaneously.

4. Drug Product
• The drug product SB309 is provided as a
liquid ready-to-use solution in a single-
dose prefilled syringe. It is formulated
based on epoetin zeta as active
ingredient at concentrations of 3,333
IU/mL, 10,000 IU/mL and 40,000 IU/mL.
• Eleven dosage strengths are provided
from 1,000 IU to 40,000 IU/syringe
dependent of different filling volumes
(0.3 to 1.0 mL).

5. What is Retacrit used for ?
• to treat anaemia that is causing symptoms in patients with chronic
kidney diseases (CKD’s).
• 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.
• to reduce the need for blood transfusions in patients with moderate
anaemia about to undergo major bone surgery (such as a hip or knee
replacement).

6. How is Retracrit used ?
• For patients with kidney problems, Retacrit 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.
• The related dose, the frequency of injection and how long Retacrit is
used for depend on why it is being used, and are adjusted according
to the patient’s response

7. CASE STUDIES
• Retacrit was studied to show that it is comparable with the reference medicine, Eprex / Erypo, in
experimental models and in humans.
• In the first study Retacrit was injected into a vein & compared with the reference medicine in two
main studies involving 922 patients who had anaemia associated with chronic renal failure
requiring haemodialysis. The first study compared the effects of Retacrit with those of Eprex /
Erypo in correcting red blood cell counts in 609 patients over 24 weeks. The second study
compared the effects of Retacrit 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 Retacrit 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.
• RESULTS : Retacrit 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 Retacrit and when they were receiving Eprex / Erypo. In both
studies, the dose of epoetin received was similar with both medicines.

8. • Hospira also conducted two more studies which observed the effects
of Retacrit injected under the skin: one involved 261 cancer patients
receiving chemotherapy, and the other compared Retacrit with Eprex
/ Erypo in 462 patients with anaemia caused by kidney problems.
• RESULTS: Retacrit was also effective when it was injected under the
skin. The study in patients receiving chemotherapy showed that
Retacrit brought about similar improvements in haemoglobin levels
as those reported in the scientific literature for other epoetins.
Retacrit was also as effective as the reference medicine in patients
with kidney problems.

9. Risks associated
• As with other medicines containing epoetin, the most common side effect
with Retacrit is an increase in blood pressure, which can sometimes lead to
symptoms of encephalopathy (brain problems) such as sudden stabbing
migraine-like headache and confusion.
• Retacrit can also lead to skin rash and influenza (flu)-like symptom.
• Retacrit should not be used in people who may be 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), 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.

10. • Uncommon side effect- Cerebral haemorrhage
These may affect 1 to 10 in every 1,000 people using Retacrit.
• Rare side effects- Increased levels of small blood cells (called
platelets), which are normally involved in the formation of a blood
clot may occur. These may affect less than 1 in 10,000 people using
Retacrit.

11. Retracrit Approval
• Both single and multiple-dose pharmacokinetic and
pharmacodynamic studies supported the biosimilar application for
Retacrit & thus it was approved for marketing & use by The
Committee for Medicinal Products for Human Use (CHMP) and the
European Commission, which approves pharmaceuticals for use in
Europe in late 2007.
• Hospira launched the product, the company’s first marketed similar
biologic, in various EU countries beginning in early 2008.

12. Retacrit Approval in U.S.A
• Hospira on Dec 16, 2014 submitted the biosimilar application to FDA,
under the new 351(k) approval pathway created by the Biologics Price
Competition and Innovation Act of 2009.
• The drug is under approval consideration process.

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