PCSK9 Inhibitors: Remarkable Drugs, Many Unknowns

November 4, 2015
Veronica Hackethal, MD
Veronica Hackethal, MD

In this short set of slides we review the potential for widespread impact by PCSK9 inhibitors on CV health as well as issues that may keep progress slow.

The remarkable LDL-C-lowering impact of the PCSK9 inhibitors (PCSK9-I) evolocumab and alirocumab and their auspicious safety profile might suggest a blockbuster future for the recently approved monoclonal antibodies. The FDA imprimatur was given, however, amid strong resistance on the grounds that their true test of efficacy, yet to come, will be whether they have a direct and positive impact on cardiovascular outcomes.Other unknowns about the PCSK9-I are reviewed in the slide show above and include: ► Will the indication be expanded to include the statin-intolerant population?  ► What about early reports of neurocognitive impact? ► Can they be made affordable? Will insurance companies negotiate?Are your colleagues discussing the new drugs? What is your prediction about their future?  

References:

1. Four things to know about PSCK9 inhibitors. Accessed October 21 2015 at: https://www.optum.com/thought-leadership/4-things-about-PCSK9-inhibitors.html

2. Everett BM, Smith RJ, Hiatt WR. Reducing LDL with PCSK9 inhibitors-The clinical benefit of lipid drugs. N Engl J Med. 2015;373:1588-1591. DOI: 10.1056/NEJMp1508120 (Free full text)

3. Institute for Clinical and Economic Review. Comparative Effectiveness Public Advisory Council. PSCK9 inhibitors for the control of high cholesterol: effectiveness, value, and value-based bench marks. Technology assessment. September 8, 2015.   

4. Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: Rationale and design of the ODYSSEY Outcomes trial.  Am Heart J. 2014;168:682–689.e1 (Abstract)

5. Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk  ClinicalTrials.gov Identifier: NCT01764633.

6. Li C, Lin L, Zhang W, et al. Efficiency and safety of proprotein convertase subtilisin/kexin 9 monoclonal antibody on hypercholesterolemia: a meta-analysis of 20 randomized controlled trials. J Am Heart Assoc. 2015;4:e001937. doi: 10.1161/JAHA.115.001937. (Free full text)