Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study (BRD4i)

This will be a 10 patient Phase 1 pilot study in Quebec and Calgary in patients with pulmonary arterial hypertension (PAH). Open label. All patients will get apabetalone for 16 weeks. At baseline and week 16, a cardiac catheterization and MRI will assess changes in pulmonary hemodynamics and RV function. Not yet recruiting. Estimated start date November 2018; estimated completion mid-2020.

https://clinicaltrials.gov/ct2/show/NCT03655704

https://trialbulletin.com/lib/entry/ct-03655704

Recall, Resverlogix has been exploring the benefits of apabetalone on PAH in pre-clinical studies and previously conveyed that 1) the effect of apabetalone on cells and in an animal model of PAH was positive; 2) three universities were collaborating on this work and working on paper now; and 3) there is even discussion about funding for that trial. I think these statements were made at last December's AGM.

An apabetalone/PAH abstract was presented at the American Thoracic Society 2018 International Conference May 18-23, 2018 in San Diego. The research focused on the beneficial effects of apabetalone on PAH endpoints in both human pulmonary artery smooth muscle cells as well as an in vivo rat model of PAH. The work was done in collaboration with the Pulmonary Hypertension Research group, CRIUCPQ, Quebec City, Canada and presented by Eve Tremblay from that institution. Here's a link to the abstract.

Apabetalone (RVX-208) Alone and in Combination with Standard of Care Improves Experimental PAH in Sugen-Hypoxia Rat Model

They observed beneficial effects in both the human cell model and the in vivo rat model. The last sentence is exciting:

"Given that Apabetalone is in a phase 3 trial of MACE outcomes in cardiovascular disease, our study supports the development of an early proof of concept clinical trial in PAH patients"

GSK also recently published in a rat model that their pan-BET inhibitor I-BET151 elicited benefits on pulmonary hypertension and COPD.

Inhibition of BET Proteins Reduces Right Ventricle Hypertrophy and Pulmonary Hypertension Resulting from Combined Hypoxia and Pulmonary Inflammation

https://www.ncbi.nlm.nih.gov/pubmed/30061518

Importantly, pan-BET inhibitors have major side effects and do not seem appropriate for long-term use. In the I-BET151 study cited above, they only dosed for 7 days in rats. Apabetalone is not a pan-BET inhibitor but is a bromodomain-2 selective BET inhibitor. Apabetalone has been shown to be safe for long-term use and some patients have been dosed for over 33 months so far. So a BD2-selective inhibitor like apabetalone would be more amenable to chronic use.

Now the question is, which of the 3 trials (Fabry, Renal, PAH) that are all listed on ClincialTrials.gov but not yet recruiting will start first?

BearDownAZ