Update on PCSK9s

Inside Edge Consulting, Princeton

March 31, 2015

The American College of Cardiology (ACC) Scientific Sessions were held last week, at which there were many exciting presentations regarding the PCSK9 inhibitors. Offered were updates on Phase 3 studies for alirocumab and evolocumab, and Phase 2 data was presented on LY3015014. Just following ACC, Phase 2b data was presented on ETC-1002. This category of cholesterol management is definitely heating up.

Those in the industry feel that PCSK9 development has been very rapid and promoted the understanding of LDL-C metabolism. PCSK9 was first identified in 2003 and the first products will be launched in 2015; this is almost unheard of in terms of speed to market.

Overall, the data presented for these three agents show that they are safe and efficacious for the reduction of LDL-C in patients. There are no statistically significant side effects over the standard of care used in these trials. However, questions from the audiences at these presentations did note three concerns for integration of these agents into clinical practice, including:

  • Understanding of any possible neurocognitive side effects as a result of sustained low LDL-C, with some patients reaching LDL-C < 30
  • The ability to define statin intolerant patients who are a key target for these agents. This will be a key factor for payer reimbursement and no standard definition exists at this time
  • Price
  • While the last factor may be the most important concernsurrounding launch of these drugs, the first two are keys to making sure the patients are treated safely and effectively.

    In the coming months we will have the opportunity to learn more about these four agents and their importance to patient health.

    For more information on these agents please view the following links:

  • Alirocumab: http://www.nejm.org/doi/full/10.1056/NEJMoa1501031
  • Evolocumab: http://www.nejm.org/doi/full/10.1056/NEJMoa1500858
  • LY3015014: http://content.onlinejacc.org/article.aspx?articleid=2197797
  • ETC-1002: http://investor.esperion.com/releasedetail.cfm?ReleaseID=901971
  • Market dynamics: http://www.nejm.org/doi/full/10.1056/NEJMe1502192

  • ACC, American College of Cardiology, Cholesterol, Consultant group, Lipids, PSCK9