PhaseBio Exploratory Trial Assesses Potential PAH Treatment

PhaseBio Pharmaceuticals has enrolled and dosed its first patient with pulmonary arterial hypertension (PAH) in a Phase 1 clinical study assessing the safety, tolerability and hemodynamic response to its PAH drug candidate PB1046. Participants are all adult PAH patients with a permanently implanted hemodynamic monitor (CardioMEMS HF System).

PB1046, an experimental therapy, is a once-weekly vasoactive intestinal peptide (VIP) agonist fused with PhaseBio’s elastin-like polypeptide (ELP) biopolymer.

VIP is a naturally occurring 28-amino acid neuropeptide that binds to two VIP receptors (VPAC1 and VPAC2) in the pulmonary, cardiovascular and immune systems. It helps regulate blood pressure and can widen blood vessels. The drug also has antifibrotic properties, making it ideal for cardiopulmonary disorders such as pulmonary hypertension that are linked to changes in VIP properties or concentration.

ELP technology is used to enhance a molecule’s effectiveness and reduce side effects. In PB1046, this technology allowed the creation of the only stable, long-acting form of VIP, overcoming the poor in vivo stability and bioavailability of the natural VIP.

PB1046 was designed to bind preferentially to the VPAC2 receptor. This minimizes potential gastrointestinal side effects thought to be associated with excessive activation of the VPAC1 receptor.

“Previous studies have demonstrated that reduced VIP levels may be a critical factor in PAH disease development and progression,” John Lee, chief medical officer of PhaseBio, said in a press release. “Consequently, VIP-based therapies such as PB1046 have the potential to provide benefit to patients who currently lack adequate treatment options.”

The current exploratory, open-label, single cohort study (NCT03315507) will also assess what happens to the drug while in patients’ bodies, as well as   exercise capacity via the six-minute walk distance test, along with exploratory biomarkers.

“We are delighted to announce the dosing of the first patient in our PAH program,” Lee said. “This marks a significant step toward our goal of building a portfolio of clinical-stage therapies that treat orphan cardiovascular disorders.”

Data obtained from this study is expected to support a placebo-controlled Phase 2 trial, planned for next year. PhaseBio is also evaluating PB1046 in a Phase 2a multiple ascending dose study (NCT02808585) in patients with heart failure.