The Therapeutic Goods Administration (TGA) has approved two novel lipid-lowering agents: evolocumab and alirocumab. Both medications are fully human monoclonal antibodies that inhibit the action of proprotein convertase subtilisin kexin type 9 (PCKS9). PCSK9 is a protease that reduces hepatic low-density lipoprotein (LDL) receptor density, thereby reducing LDL clearance from the blood. Expression of PCSK9 is increased during statin therapy, attenuating treatment efficacy. Inhibition of PCKS9 offers an alternative, and possibly synergistic, pathway for reducing circulating levels of atherogenic lipoproteins in the blood.
When added to statin therapy, PCKS9 inhibitors reduce LDL levels by 40% to 70%. This is in contrast to the 24% reduction demonstrated by ezetimibe. The clinical benefit of this requires more study, although preliminary results indicate significant cardioprotective effects. Major cardiovascular adverse events occurred in 0.95% of evolocumab patients (2.18% placebo) and 1.7% of alirocumab patients (3.3% placebo).
Maximal doses of statins reduce LDL levels by around 60%. Therefore, PCKS9 inhibitors should only be prescribed for patients who are statin-intolerant or who fail to achieve target lipid levels with maximal statin doses. Alirocumab and evolocumab are administered by subcutaneous injection to the thigh, abdomen, or upper arms. Neither medication is currently listed on the Pharmaceutical Benefits Scheme (PBS). However, evolocumab received a positive recommendation at the Pharmaceutical Benefits Advisory Committee (PBAC) meeting in March 2016.
- Praluent® (alirocumab) Australian approved product information. Macquarie Park: Sanofi-Aventis Australia. Approved May 2016.
- Repatha™ (evolocumab) Australian approved product information. North Ryde: Amgen. Approved December 2015.
- Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372(16): 1489-99.
- Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372: 1500-9.
- Sijbrands EJ. Inhibition of PCKS9 in familial hypercholesterolaemia. Lancet. 2012; 380(9836): 6-7.