REPATHA ® ( evolocumab ) BRIEF SUMMARY OF PRESCRIBING INFORMATION Please see package insert for full Prescribing Information
1 . INDICATIONS AND USAGE 1.1 Primary Hyperlipidemia
REPATHA is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia ( HeFH ) or clinical atherosclerotic cardiovascular disease ( CVD ), who require additional lowering of low density lipoprotein cholesterol ( LDL-C ).
1.2 Homozygous Familial Hypercholesterolemia
REPATHA is indicated as an adjunct to diet and other LDL-lowering therapies ( e . g ., statins , ezetimibe , LDL apheresis ) for the treatment of patients with homozygous familial hypercholesterolemia ( HoFH ) who require additional lowering of LDL-C .
1.3 Limitations of Use
The effect of REPATHA on cardiovascular morbidity and mortality has not been determined .
4 . CONTRAINDICATIONS
REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to REPATHA [ see Warnings and Precautions ( 5.1 )].
5 . WARNINGS AND PRECAUTIONS 5.1 Allergic Reactions
Hypersensitivity reactions ( e . g ., rash , urticaria ) have been reported in patients treated with REPATHA , including some that led to discontinuation of therapy . If signs or symptoms of serious allergic reactions occur , discontinue treatment with REPATHA , treat according to the standard of care , and monitor until signs and symptoms resolve .
6 . ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label :
• Allergic Reactions [ see Warnings and Precautions ( 5.1 )] 6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice .
Adverse Reactions in Patients with Primary Hyperlipidemia and in Patients with Heterozygous Familial Hypercholesterolemia
REPATHA is not indicated for use in patients without familial hypercholesterolemia or atherosclerotic CVD [ see Indications and Usage ( 1.1 )].
The data described below reflect exposure to REPATHA in 8 placebo-controlled trials that included 2651 patients treated with REPATHA , including 557 exposed for 6 months and 515 exposed for 1 year ( median treatment duration of 12 weeks ). The mean age of the population was 57 years , 49 % of the population were women , 85 % White , 6 % Black , 8 % Asians , and 2 % other races .
Adverse Reactions in a 52-Week Controlled Trial
In a 52-week , double-blind , randomized , placebo-controlled trial ( Study 2 ), 599 patients received 420 mg of REPATHA subcutaneously once monthly [ see Clinical Studies ( 14.1 )]. The mean age was 56 years ( range : 22 to 75 years ), 23 % were older than 65 years , 52 % women , 80 % White , 8 % Black , 6 % Asian , and 6 % Hispanic . Adverse reactions reported in at least 3 % of REPATHAtreated patients , and more frequently than in placebo-treated patients in Study 2 , are shown in Table 1 . Adverse reactions led to discontinuation of treatment in 2.2 % of REPATHA-treated patients and 1 % of placebo-treated patients . The most common adverse reaction that led to REPATHA treatment discontinuation and occurred at a rate greater than placebo was myalgia ( 0.3 % versus 0 % for REPATHA and placebo , respectively ).
Table 1 . Adverse Reactions Occurring in Greater than or Equal to 3 % of REPATHA-treated Patients and More Frequently than with Placebo in Study 2
Placebo ( N = 302 ) %
REPATHA ( N = 599 ) %
Nasopharyngitis |
9.6 |
10.5 |
Upper respiratory tract infection |
6.3 |
9.3 |
Influenza |
6.3 |
7.5 |
Back pain |
5.6 |
6.2 |
Injection site reactions † |
5.0 |
5.7 |
Cough |
3.6 |
4.5 |
Urinary tract infection |
3.6 |
4.5 |
Sinusitis |
3.0 |
4.2 |
Headache |
3.6 |
4.0 |
Myalgia |
3.0 |
4.0 |
Dizziness |
2.6 |
3.7 |
Musculoskeletal pain |
3.0 |
3.3 |
Hypertension |
2.3 |
3.2 |
Diarrhea |
2.6 |
3.0 |
Gastroenteritis |
2.0 |
3.0 |
† includes erythema , pain , bruising |
|
|
Adverse Reactions in Seven Pooled 12-Week Controlled Trials |
In seven pooled 12-week , double-blind , randomized , placebo-controlled trials , |
993 patients received 140 mg of REPATHA subcutaneously every 2 weeks and |
1059 patients received 420 mg of REPATHA subcutaneously monthly . The mean |
age was 57 years ( range : 18 to 80 years ), 29 % were older than 65 years , 49 % |
women , 85 % White , 5 % Black , 9 % Asian , and 5 % Hispanic . Adverse reactions |
reported in at least 1 % of REPATHA-treated patients , and more frequently than |
in placebo-treated patients , are shown in Table 2 . |
Table 2 . Adverse Reactions Occurring in Greater than 1 % of REPATHA-treated |
Patients and More Frequently than with Placebo in Pooled 12-Week Studies |
Placebo ( N = 1224 ) %
REPATHA †
( N = 2052 ) %
Nasopharyngitis |
3.9 |
4.0 |
Back pain |
2.2 |
2.3 |
Upper respiratory tract infection |
2.0 |
2.1 |
Arthralgia |
1.6 |
1.8 |
Nausea |
1.2 |
1.8 |
Fatigue |
1.0 |
1.6 |
Muscle spasms |
1.2 |
1.3 |
Urinary tract infection |
1.2 |
1.3 |
Cough |
0.7 |
1.2 |
Influenza |
1.1 |
1.2 |
Contusion |
0.5 |
1.0 |
|
†
140 mg every 2 weeks and 420 mg once monthly combined
|
Adverse Reactions in Eight Pooled Controlled Trials ( Seven 12-Week Trials and One |
52-Week Trial ) |
The adverse reactions described below are from a pool of the 52-week trial ( Study 2 ) |
and seven 12-week trials . The mean and median exposure durations of REPATHA in |
this pool of eight trials were 20 weeks and 12 weeks , respectively . |
Local Injection Site Reactions |
Injection site reactions occurred in 3.2 % and 3.0 % of REPATHA-treated and |
placebo-treated patients , respectively . The most common injection site reactions |
were erythema , pain , and bruising . The proportions of patients who discontinued |
treatment due to local injection site reactions in REPATHA-treated patients and |
placebo-treated patients were 0.1 % and 0 %, respectively . |
Allergic Reactions |
Allergic reactions occurred in 5.1 % and 4.7 % of REPATHA-treated and placebotreated |
patients , respectively . The most common allergic reactions were rash ( 1.0 % |
versus 0.5 % for REPATHA and placebo , respectively ), eczema ( 0.4 % versus 0.2 %), |
erythema ( 0.4 % versus 0.2 %), and urticaria ( 0.4 % versus 0.1 %). |
Neurocognitive Events |
In placebo-controlled trials , neurocognitive events were reported in less than or |
equal to 0.2 % in REPATHA-treated and placebo-treated patients . |