| Drug name | Repatha®
|
| INN | Evolocumab |
| API type | Monoclonal antibody |
Pharmacotherapeutic group
| Lipid modifying agents, other lipid modifying agents |
ATC code
| C10AX13 |
Target of antibody
| PCSK9 |
| General function | |
| Short description | Evolocumab is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, and in paediatric patients aged 10 years and over with heterozygous familial hypercholesterolaemia, as an adjunct to diet.
It is also indicated in adults and paediatric patients aged 10 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies as well as in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors. |
Pharmacodynamic properties
(Mechanism of action; Source EMA document)
| Evolocumab binds selectively to PCSK9 and prevents circulating PCSK9 from binding to the low density lipoprotein receptor (LDLR) on the liver cell surface, thus preventing PCSK9-mediated LDLR degradation. Increasing liver LDLR levels results in associated reductions in serum LDL-cholesterol (LDL-C). |
| Pharmacodynamic properties (Pharmacodynamic effects; Source EMA document) | In clinical trials, evolocumab reduced unbound PCSK9, LDL-C, TC, ApoB, non-HDL-C, TC/HDL-C, ApoB/ApoA1, VLDL-C, TG and Lp(a), and increased HDL-C and ApoA1 in patients with primary hypercholesterolaemia and mixed dyslipidaemia.
A single subcutaneous administration of 140 mg or 420 mg evolocumab resulted in maximum suppression of circulating unbound PCSK9 by 4 hours followed by a reduction in LDL-C reaching a mean nadir in response by 14 and 21 days, respectively. Changes in unbound PCSK9 and serum lipoproteins were reversible upon discontinuation of evolocumab. No increase in unbound PCSK9 or LDL-C above baseline was observed during the washout of evolocumab suggesting that compensatory mechanisms to increase production of PCSK9 and LDL-C do not occur during treatment.
Subcutaneous regimens of 140 mg every 2 weeks and 420 mg once monthly were equivalent in average LDL-C lowering (mean of weeks 10 and 12) resulting in -72% to -57% from baseline compared with placebo. Treatment with evolocumab resulted in a similar reduction of LDL-C when used alone or in combination with other lipid-lowering therapies. |
Original license holder
| Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands |
Marketing authorisation numbers
| EU/1/15/1016/003
|
Marketing authorisation holder
| Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands |
Name of the manufacturer of the biological active substance
| Amgen Manufacturing Limited
Road 31 km 24.6
Juncos
Puerto Rico, 00777
United States
Immunex Rhode Island Corporation
40 Technology Way
West Greenwich
Rhode Island, 02817
United States
|
| Name and address of the manufacturer(s) responsible for batch release | Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Co Dublin
Ireland
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium
|
Max shelf life
| 36 months |
Storage conditions
| 2°C – 8°C
|
List of excipients
| Proline
Glacial acetic acid
Polysorbate 80
Sodium hydroxide (for pH adjustment)
Water for injections |
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