STRAIGHT TALK
STEVEN E. NISSEN, MD
First PCSK9 Inhibitors
Approved: What’s Next?
I
n July 2015, the FDA approved a PCSK9 inhibitor, the first major new class of lipid-modulating
medications since the introduction of the statins
in 1987. During the last 28 years, many promising
therapies entered initial clinical development, but each
failed to demonstrate either safety or efficacy (or both)
during pre-clinical studies or human trials. Some
development programs collapsed dramatically due
to unexpected toxicity (torcetrapib), whereas others
(darapladib, dalcetrapib) simply failed to show evidence of meaningful clinical benefit. Even previously
accepted therapies such as niacin have come under
scrutiny as a consequence of contemporary clinical
trials that showed both lack of effectiveness and significant adverse effects. Arguably, even the PCSK9 inhibitors have yet to demonstrate a reduction in major
cardiovascular events, although most knowledgeable
observers consider a near certainty the likelihood of
favorable conclusions from ongoing clinical trials.
Now that nearly 3 decades of drought has
finally ended, what will the next few years bring?
Are any other major new approaches to treatment
of lipids likely to succeed? Currently available
preclinical and genetic data suggest t H\