Re: NIH Halts Large Cardiovascular Inflammation Reduction Trial (CIRT)
in response to
by
posted on
Sep 23, 2018 01:42PM
No problem Tada. I like to discuss these trials before they read out so that the readers here are prepared to put these trial results in proper context when the results do come out.
REDUCE-IT likely reads out top-line data this week (end of September guidance) and CIRT reads out in November at AHA. Those may be the only two CVOTs with any relevance to apabetalone/BETonMACE reading out before BETonMACE top LINE reads out in Q1 2019.
One of apabetalone's many beneficial effects is its anti-inflammatory properties, which creates some overlap with CIRT's methotrexate mechanism of action. In my opinion, success or failure of CIRT will have little bearing on Apabetalone/BETonMACE. CANTOS was a cleaner CVOT that already supported the inflammation hypothesis. If CIRT succeeds, great....more support for the inflammation hypothesis. If CIRT fails, oh well..... it was a crude drug with many side effects concerns anyways.
Although apabetalone hasn't been shown to reduce plasma triglycerides like Amarin's Vascepa in the REDUCE-IT trial, both trials include diabetic/metabolic syndrome patients with hypertriglyceridemia. BETonMACE allows patients with up to 400 mg/dL baseline plasma TG (no minimum TG requirement); REDUCE-IT only allows patients in the 150-500 mg/dL baseline TG range. No overlap in mechanism of action between apabetalone (BD2-selective BET inhibitor) and Vascepa (purified omega 3 EPA). However, if apabetalone does improve insulin sensitivity and/or reduce liver fat accumulation, then apabetalone treated patients may experience a lowering of their plasma triglycerides. Personally, I'm cheering for REDUCE-IT to succeed and validate the TG hypothesis, but success or failure of REDUCE-IT really has no bearing on Apabetalone/BETonMACE.
BETonMACE is unique in that patients are required to have diabetes, required to have low HDL and required to have cardio event within 90 days of first screening. So absolute risk is highest in BETonMACE patients compared to CIRT, REDUCE-IT and most other CVOTs to date. If successful, BETonMACE will make a splash because of its effects on both relative and absolute CVD risk reductions. Plus the renal and cognitive endpoints of BETonMACE are potentially an added bonus.
BearDownAZ