Abstract
BackgroundPCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries.MethodsAlirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA.ResultsAverage subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was − 5.8 ± 4.4% (P = 0.005) and − 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and − 9.7 ± 11.8% (P = 0.04) and − 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were − 5.2 ± 2.9% (P = 0.001) and − 2.6 ± 4.9% (P = 0.16) for alirocumab, and − 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab.ConclusionProper drug storage according to manufacturer’s recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.
Highlights
PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels
All 9 study patients were diagnosed with dyslipidemia and were prescribed lipid lowering medications other than PCSK9 monoclonal antibody
Heated-unheated condition Previous study showed that temperature higher than 72 °C for more than 1.5 min resulted in degradation of monoclonal antibodies [13, 14]
Summary
PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8 °C, and not above 25 °C. There is strong evidence that elevated plasma low-density lipoprotein cholesterol (LDL-C) level has a causal relationship with risk of developing atherosclerotic cardiovascular disease (ASCVD) [1]. PCSK9 monoclonal antibody (PCSK9 mAb) lowers plasma PCSK9 levels, which prevents LDLR degradation and increases the number of LDLR available to lower low-density lipoprotein in plasma [3]. Two PCSK9 monoclonal antibodies, alirocumab and evolocumab, are currently commercially available These drugs are indicated as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with familial hypercholesterolemia (FH), with clinical atherosclerotic cardiovascular disease, in those who require additional lowering of plasma LDL-C, or in those who are statin intolerant [1, 9]
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