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Spotlight on: Jay D. Horton, MD & PCSK9 Inhibitors

Jay D. Horton, MD, CMHC keynote speaker and lead researcher among the original teams that cloned the PCSK9 gene before its function was realized, talked with CMHC recently about the rapid development of PCSK9 inhibitors, the first of which, Regeneron/Sanofi?s alirocumab, has just received FDA approval ? just 12 years after the PCSK9 gene was identified. Having the ability to lower LDL-C levels by about 70%, PCSK9 inhibitors are set to be a gamechanger. Phase 3 cardiovascular outcomes trials are ongoing, with completion likely in late 2017.

?The combination of determining how PCSK9 functioned, where it functioned, along with the genetics that proved inhibiting the protein would have a positive benefit down the road on improving cardiovascular outcomes was the reason pharmaceutical companies immediately caught on this was a surefire drug target,? Dr. Horton said. He pointed to a few other key events that allowed for rapid development of the drug as well: the discovery that PCSK9 is secreted in the blood, and functions outside the cell, and binds to the LDL receptors on the cell surface. PCSK9 also did not behave as other proteases typically do by degrading their target protein. Instead, PCSK9 binds to its target: the LDL receptor, which is subsequently taken into the lysosome of the cell and destroyed. ?Because PCSK9 is secreted in the blood and works extracellularly, an opportunity to develop antibodies was created. These antibodies can function in the blood and block the interaction of PCSK9 with the LDL receptor, essentially resulting in an inhibitor of the PCSK9 protein.?

At #CMHC2015, Dr. Horton will deliver the Keynote ?Genetics to Therapeutics: The Role of PCSK9? on Thursday, October 22. Plan on attending to learn more on their fascinating history and development. Join us later that evening for a Deep Dive Symposium titled ?Novel Therapies for LDL-C Lowering in the Fight Against Residual ASCVD Risk? - an in-depth CME session with our expert faculty, including the lead investigator from the ODYSSEY Long-Term Study, Jennifer G. Robinson, MD, MPH.

Stay tuned! Amgen?s evolocumab is up next, later this summer.

Learn more about these important clinical advances at the 10th Annual CMHC.

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