How Long Before Repatha Works
Repatha (evolocumab) begins lowering LDL cholesterol within 4 weeks of initiation, with peak LDL-C reduction occurring approximately 1 week after each 140 mg dose (given every 2 weeks) or 2 weeks after each 420 mg dose (given monthly). 1, 2
Onset of Action
The FDA label states that the LDL-lowering effect of Repatha may be measured as early as 4 weeks after initiation. 1
The pharmacodynamic effects on PCSK9 are rapid, with maximum PCSK9 suppression occurring within 4 hours of administration. 2
At steady state, peak LDL-C reduction occurs approximately 1 week after a subcutaneous dose of 140 mg every 2 weeks and 2 weeks after a 420 mg monthly dose. 2
Magnitude of LDL-C Reduction
Evolocumab reduces LDL-C by approximately 59-64% when added to maximally tolerated statin therapy. 3
In the FOURIER trial, baseline median LDL-C of 92 mg/dL was reduced by 59% to a median value of 30 mg/dL at 48 weeks. 3, 4
Both the 140 mg every 2 weeks and 420 mg monthly regimens provide comparable LDL-C reduction (64% and 58% respectively). 3, 5
Peak and Trough Effects
Peak LDL-C reduction is approximately 73% for the 140 mg every 2 weeks regimen and 69% for the 420 mg monthly regimen. 6
LDL-C levels return toward baseline over the dosing interval, with median peak-trough variability of approximately 20.5% for 140 mg every 2 weeks and 21.1% for 420 mg monthly. 6
When monitoring LDL-C for patients receiving 420 mg monthly, the FDA recommends measuring LDL-C just prior to the next scheduled dose, as LDL-C can vary during the dosing interval. 1
Clinical Implications
The rapid onset allows for relatively quick assessment of treatment response, with meaningful LDL-C measurements possible at 4 weeks. 1
The sustained LDL-C reduction with approved doses (140 mg every 2 weeks or 420 mg monthly) provides greater stability compared to lower doses. 6
For patients with homozygous familial hypercholesterolemia, if a clinically meaningful response is not achieved in 12 weeks with 420 mg monthly, the dose can be increased to 420 mg every 2 weeks. 5, 1