Abbvie has a trial listed on ClinicalTrials.gov for ABBV-744 that is not yet recruiting. First listed December 2017 with anticipated start end of Feb 2018.

A Study Evaluating the Safety and Pharmacokinetics of ABBV-744 in Subjects With Advanced Prostate Cancer (CRPC) and Relapsed/Refractory Acute Myeloid Leukemia (AML) Cancer

To my knowledge, that will be the first cancer trial using a bromodomain-selective BET inhibitor. Abbvie claims in their AACR abstract that ABBV-744 has 300-fold selectivity for BD2 of BRD4 over BD1 of BRD4. The 2013 paper by Picaud et al. investigated the BD2 selectivity of RVX-208. However, without a side by side comparison of ABBV-744 and RVX-208 using the same methodology, I don't think it is fair to compare the two. Safe to say both are BD-2 selective BET inhibitors.

This raises 3 obvious questions:

1) If RVX-208 (apabetalone) proves promising in BETonMACE for reducing cardiovascular events, will Abbvie's ABBV-744 be the first potential competitor for apabetalone? Of course, ABBV-744 would need to prove itself in Phase 1, 2 and 3 trials first.

2) In the ABBV-744 abstract, Abbvie states "In striking contrast to the broad range of cell growth inhibition effected by pan BET inhibitor ABBV-075, the anti-proliferative activity for BDII-selective ABBV-744 was largely but not exclusively restricted to AML and androgen receptor (AR) positive prostate cancer cell line models, including models of Enzalutamide resistance." Does the BD-2 selective RVX-208 have this anti-proliferative activity in cancer cells seen with BD-2 selective ABBV-744?

3) Do any of the non-pan BET inhibitors owned by Resverlogix or Zenith offer anti-proliferative activity in cancer cells? If so, do they circumvent the side-effects/toxicity observed with pan-BET inhibitors?

Side note: Gilead's Phase 1/2 trials in mCRPC and HER2-negative breast cancer with their BET inhibitor GS-5829 are now both in the active but not recruiting stage. So in addition to Zenith, we have Abbvie, Gilead and Incyte all with Phase 1/2 trials for mCRPC. I previously posted a complilation of ongoing BET clinical trials (outdated but still relevant to the most advanced ones). GSK and BMS also seem to have Phase 1/2 trials ongoing, but not explicitly mCRPC. 

The race is on!

BDAZ