Resverlogix Obtains Funding for Phase 2 Trial Testing Apabetalone in PAH

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by Santiago Gisler |

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Resverlogix announced that it has received funding from the Canadian Institutes for Health Research for a Phase 2 clinical study investigating the safety and efficacy of its proprietary therapy apabetalone (RVX-208) as a potential treatment for pulmonary arterial hypertension (PAH).

Resverlogix will match the new funding, including in-kind (not involving money, e.g., goods, services, or transactions) and direct investment.

According to a press release, the company plans to start the Phase 2 study testing apabetalone for the treatment of PAH after the completion of a pilot study starting in the first half of this year. The $2.9 million project will be led by collaborators at Quebec Heart and Lung Institute, part of Laval University, Canada.

The planned Phase 2 trial is based on evidence suggesting the involvement of a group of epigenetic proteins (proteins that control gene activity without changing the genetic codes), called bromodomain and extra-terminal domain (BET) proteins, in the progression of PAH.

BET proteins are so-called epigenetic readers that recognize a specific acetyl group (a chemical compound) tagged on DNA-associated proteins called histones. Upon recognition, BET proteins can recruit other proteins to the genetic location and activate gene expression (activity).

In certain clinical conditions, uncontrolled levels of BET proteins can cause increased production of other proteins contributing to diseases.

Join the PH forums: an online community especially for patients with pulmonary hypertension.

Studies in animal models showed reversed PAH upon inhibition of a specific BET protein called BRD4. According to these studies, BET inhibition resulted in reduced proliferation of arterial smooth muscle cells, and increased apoptosis (programmed cell death).

Importantly, the orally active BET inhibitor apabetalone has been shown to induce improved blood flow and right ventricular function in an animal model with experimentally induced PAH.

Resverlogix recently completed the Phase 3 clinical study BETonMACE (NCT02586155), testing apabetalone on high-risk cardiovascular disease patients with type 2 diabetes mellitus and low levels of high-density lipoprotein. The Data and Safety Monitoring Board — an independent group of clinical experts including physicians, statisticians, and patient advocates — has recommended a continuation of the study without modifications, based on safety information reviews.

Apart from this clinical project in PAH, the company also reported advancements in the evaluation of the inhibitor on other conditions, such as Fabry disease, a rare genetic disorder. A preclinical study using apabetalone on blood cells from Fabry disease patients is ongoing.

A Conversation With Rare Disease Advocates