Masila,

Thanks for sharing. Great question about whether Amgen's and Regeneron's injectable PCSK9 antibody therapies will also see a similar fate. According to the Pfizer press release "Pfizer has observed an emerging clinical profile that includes an unanticipated attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time, as well as a higher level of immunogenicity and higher rate of injection-site reactions with bococizumab than shown with the other agents in this class.” That implies that this attenuation, immunogenicity and irritation may be specific to bococizumab.

The ongoing cardiovascular outcomes trials for Amgen's Evolocumab (Repatha; FOURIER trial) and Sanofi/Regeneron's Alirocumab (Praluent; Odyssey Trial) are set to read out Q4 2017 to Q1 2018....so we have a while to go for those CVOT results.

As for RVX-208, we are an orally-available small molecule, so we avoid the injection site irritation issue and the immunogenicity issue. Also, we are not an LDL-lowering therapy. However, RVX-208 is a first in class BET bromodomain inhibitor selective for the second bromodomain. There is still the risk of encountering adverse reactions/side effects with prolonged treatment. Dosing started in mid November 2015, so we are almost at the one year point of dosing for the patients that started early. These patients will be dosed for up to 2 years. To the best of my knowledge, we are in unchartered waters in terms of clinical effects of prolonged BET inhibitor administration. I look forward to the next DSMB report.

BearDownAZ