Amgen struck a $300m (€268m) to buy Dezima this week, but could pay much more if the cholesteryl ester transfer protein (CETP) inhibitor achieves certain development and sales milestones.
In Phase II trials, TA-8995 reduced low-density lipoprotein cholesterol (LDL-C) by 45% compared to baseline, both on its own and in combination with statins.
CETP activity is inversely related to cardiovascular mortality, Amgen spokesperson Kristen Davies said, so the candidate inhibits CETP to reduce activity resulting in increased HDL (High-density lipoprotein) and decreased LDL levels.
“The CETP facilitates the transfer of cholesterol from HDL to other lipoproteins including LDL, in exchange for triglycerides,” Davies told in-Pharmatechnologist.com.
“The CETP mediated transfer of cholesterol into LDL particles results into maturation of those LDL particles to more atherogenic LDL particles, which contribute to macrophage foam cell, and eventually plaque formation.”
CETP vs PCSK9
The candidate is the latest in a new class of cholesterol lowering treatments. The US FDA recently approved two PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors including Amgen’s own Repatha (evolocumab).
Despite this, Dezima’s CEO Rob de Ree said in June: “We believe TA-8995 to be well positioned vis-à-vis PCSK9 antibodies in treating dyslipidemia from a perspective of efficacy, price and delivery. Besides requiring frequent injections, PCSK9 antibodies will likely be expensive and have not shown any beneficial effect on cholesterol efflux.”
But with TA-8995, Amgen’ EVP of R&D Sean harper said it will now “be able to offer more treatment options with different mechanisms of action and modes of administration across varying LDL-C levels and risk profiles.”