Product information

III.5.1 Summary of Product Characteristics

The application concerns an update to the Summary of Product Characteristics (SmPC) of EPREX®/ERYPO® to add the new indication:

EPREX, ERYPO is indicated for the treatment of anaemia (haemoglobin concentration of ≤10 g/dL) in adults with low- or intermediate-1-risk myelodysplastic syndromes (MDS).

This update involves the following proposed changes:

 The addition of a sentence in section 4.1 of the SmPC:

EPREX, ERYPO is indicated for the treatment of anaemia (haemoglobin concentration of ≤10 g/dL) in adults with low- or intermediate-1-risk myelodysplastic syndromes (MDS).

 The addition of a paragraph in section 4.2 of the SmPC:

EPREX, ERYPO should be administered to patients with anaemia (e.g. haemoglobin concentration ≤ 10 g/dL (6.2 mmol/L).

The recommended starting dose is EPREX, ERYPO 450 IU/kg (maximum total dose is 40,000 IU) administered subcutaneously once every week.

It is recommended that response be assessed at week 8. If no erythroid response is achieved after 8 weeks according to IWG 2006 criteria (see section 5.1- Pharmacodynamic properties – Clinical efficacy and safety), and the haemoglobin concentration is below 11 g/dL (6.8 mmol/L), the dose should be increased from 450 IU/kg once every week to 1050 IU/kg once every week (maximum dose is 80,000 IU per week).

Appropriate dose adjustments should be made to maintain haemoglobin concentrations within the target range of 10 g/dL to 12 g/dL (6.2 to 7.5 mmol/L). See diagram below for guidelines for stepwise dose adjustment. Epoetin alfa should be withheld or the dose reduced when the haemoglobin concentration exceeds 12 g/dL (7.5 mmol/L). Upon dose reduction, if haemoglobin concentration drops ≥1g/dL the dose should be increased.

JNJ-7472179 (epoetin alfa)

Myelodysplastic Syndromes / Type II Variation (009-010, 013-014/II/124) Health Authority Response

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A sustained haemoglobin concentration of greater than 12 g/dL (7.5 mmol/L) should be avoided.

In addition, an addition of a sentence relative to method of administration:

EPREX, ERYPO should be administered as a subcutaneous injection.

 The addition of a sentence in section 4.8 of the SmPC:

The safety profile for patients with low- or intermediate-1-risk MDS treated with EPREX, ERYPO was consistent with the known safety profile of EPREX, ERYPO. No new Adverse Drug Reactions were identified in studies in patients with MDS.

 The addition of a paragraph in section 5.1 of the SmPC:

A randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of epoetin alfa in adult anemic subjects with low- or intermediate-1-risk MDS.

Erythroid response was defined according to IWG 2006 criteria as a haemoglobin increase ≥ 1.5 g/dL from baseline or a reduction of RBC units transfused by an absolute number of at least 4 units every 8 weeks compared to the 8 weeks prior to baseline, and a response duration of at least 8 weeks.

Erythroid response during the first 24 weeks of the study was demonstrated by 27/85 (31.8%) of the subjects in the epoetin alfa group compared to 2/45 (4.4%) of the subjects in the placebo group (p<0.001).

Time to first transfusion was statistically significantly longer in the treatment group (p=0.046).

The percentage of subjects who were transfused in the treatment group decreased from 51.8% in the 8 weeks prior to baseline to 24.7% between weeks 16 and 24, compared to the placebo group which increased from 48.9% to 54.1% over the same time period.

Assessor’s comment

Concerning the EPOANE 3021 study, the MAH should mention in section 5.1 that all of the responding subjects were in the strata with serum erythropoietin less than 200 mU/ml during screening and also the higher rate of TVE in the epoietin alfa group than in placebo group in EPOANE 3021 study.

In addition, the MAH should justify the (very short) dosing recommendations proposed for section 4.2, which cover only a part of the dosing recommendations used during the study (CSP

JNJ-7472179 (epoetin alfa)

Myelodysplastic Syndromes / Type II Variation (009-010, 013-014/II/124) Health Authority Response

96 Status: Approved , Date: 27 September 2016

section 6) and are thus considered insufficient and confusing, and align accordingly ( comment).

SmPC section 4.8 should be updated with new data from pivotal study EPOANE3021, i.e.

including information about patients treated for MDS in the introductory paragraph “Of a total 3,262 subjects in 23 randomised,… studies,…” and any further concerned paragraph ( comments).

III.5.2 Package leaflet and user test

The following additions the Patient Information Leaflet (PIL) have been proposed by the MAH:

1. What EPREX is and what it is used for

EPREX is used to treat anaemia in adults with myelodysplastic syndromes. EPREX can reduce the need for a blood transfusion.

3. How to use EPREX

Adults with myelodysplastic syndrome

 Your doctor may initiate treatment with EPREX if your haemoglobin is 10 g/dL or less.

 EPREX is given by injection under the skin.

 The starting dose is 450 IU per kilogram bodyweight once a week.

 Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia responds to EPREX treatment.

 Your doctor will maintain your haemoglobin level between 10 and 12 g/dL as a high

 haemoglobin level may increase the risk of blood clots and death.

Assessor’s comment

The RMS has no comment regarding the sections 1 and 3 of the PIL.

In the section 2: “What do you need to know before you see EPREX”; in the paragraph “Take special care with EPREX”: the MAH should propose some warnings as it was recommended to patients with chronic renal failure.

No user test has been provided by the MAH.

III.5.3 Labelling

The MAH does not propose any modification of labelling.

JNJ-7472179 (epoetin alfa)

Myelodysplastic Syndromes / Type II Variation (009-010, 013-014/II/124) Health Authority Response

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