First-in-class, once-weekly VIP analogue to advance into Phase 2b clinical trial this quarter
Malvern, PA, July 10, 2018 — PhaseBio Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on the development of therapies for orphan diseases with an initial focus on cardiopulmonary disorders, today announced an update on the clinical progress of PB1046, a sustained-release vasoactive intestinal peptide (VIP) analogue being evaluated for the treatment of patients with pulmonary arterial hypertension (PAH).
“We are pleased that the findings to date from our pilot study of PB1046 in PAH patients with a permanently implanted hemodynamic monitor are consistent with the favorable tolerability and pharmacodynamic profile demonstrated in our recently completed Phase 1b/2a multiple ascending dose trial of PB1046 in patients with heart failure with reduced ejection fraction. Overall, the results from these studies support the continued evaluation of PB1046 as a once-weekly subcutaneous injection for the treatment of cardiopulmonary disorders,” said John Lee, M.D., Ph.D., Chief Medical Officer of PhaseBio. “We look forward to commencing a Phase 2b clinical trial of PB1046 in PAH later this quarter.”
In the recently completed Phase 1b/2a multiple ascending dose trial of PB1046 in patients with heart failure with reduced ejection fraction, PB1046 was dosed on top of heart failure standard-of-care medications. PB1046 was well-tolerated and did not result in any reported symptomatic hypotension or drug-related serious adverse events. In addition, investigators observed the expected dose-dependent reduction of systemic blood pressure.
PhaseBio’s ongoing open-label, individually dose-titrated study represents the first experience with PB1046 in PAH patients. This small pilot study is designed to assess the safety and tolerability of weekly subcutaneous PB1046 for eight weeks in adult patients with PAH who have a permanently implanted hemodynamic monitor (CardioMEMS™ HF System). Preliminary data from the first two research participants show that PB1046 appears to be generally well-tolerated, with no drug-related serious adverse events. Importantly, there was no symptomatic hypotension or syncope (fainting) associated with PB1046 reported in these participants on multiple PAH therapies. Moreover, there appear to be trends indicating a reduction in mean pulmonary artery pressure and total pulmonary resistance that may be associated with PB1046 dosing.
- James White, M.D., Ph.D., Professor of Medicine, Pharmacology & Physiology at the University of Rochester Medical Center, presented information about PB1046 yesterday at the 5th Annual Pulmonary Vascular Research Institute (PVRI) Drug Discovery & Development Symposium for Pulmonary Hypertension, which was co-sponsored by the U.S. Food and Drug Administration.
Dr. White said, “PAH is a rare, progressive, and often fatal disease. Despite recent therapeutic advancements, many PAH patients still progress to transplant and death. Many others are dependent on continuous infusions and would greatly benefit from simpler treatment options. Studies have suggested that VIP signaling is deficient in PAH and that VIP replacement therapy would be a useful treatment for PAH, and PB1046 is the first compound with desirable pharmaceutical characteristics and a favorable side effect profile. As a long-acting analogue of VIP targeting the VPAC2 receptor, PB1046 has the potential to be a novel therapy for PAH patients, and yesterday’s data presentation is very encouraging in this regard.”
The PB1046 pilot study in PAH is supported by a Fast Track Small Business Innovation Research grant from the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R44HL140690. The content of this press release is solely the responsibility of PhaseBio and does not necessarily represent the official views of the National Institutes of Health.
PB1046 is a once-weekly vasoactive intestinal peptide (VIP) receptor agonist that targets VPAC receptors in the cardiovascular, pulmonary and immune systems. VIP is known to have vasodilatory, inotropic, lusitropic and anti-inflammatory effects and several cardiopulmonary disorders are associated with alterations in levels of VIP or its receptors, VPAC1 and VPAC2. Consequently, VIP-based therapies are expected to provide benefit in pulmonary arterial hypertension (PAH), cardiomyopathy and other cardiovascular diseases.
PB1046, which comprises an analogue of VIP fused to PhaseBio’s elastin-like polypeptide (ELP) biopolymer, is designed to overcome the poor in vivo stability and bioavailability of the native VIP peptide, and to preferentially bind to the VPAC2 receptor to minimize potential gastrointestinal side effects. PB1046 was well-tolerated and demonstrated a prolonged, dose-dependent effect on blood pressure in a Phase 1 clinical trial in patients with essential hypertension, and demonstrated clear efficacy in animal models of heart failure, PAH and Duchenne muscular dystrophy-related cardiomyopathy.
The U.S. Food and Drug Administration has granted PB1046 orphan drug designation for the treatment of PAH (WHO Group 1 Pulmonary Hypertension) and cardiomyopathy associated with dystrophinopathies.
PhaseBio Pharmaceuticals, Inc., is a clinical-stage biopharmaceutical company focused on the development of therapies for the treatment of orphan diseases, with an initial focus on cardiopulmonary disorders. The company’s lead development candidate is PB2452, a reversal agent for the antiplatelet therapy ticagrelor. PhaseBio is also leveraging its proprietary elastin-like polypeptide (ELP) biopolymer technology platform to develop therapies with the potential for less-frequent dosing and better patient compliance. PhaseBio’s development candidate based on ELP, PB1046, is a first-in-class weekly vasoactive intestinal peptide (VIP) receptor agonist for the treatment of pulmonary arterial hypertension. PhaseBio is privately owned, with headquarters and research laboratories in Malvern, PA. For more information, please visit www.phasebio.com.
Laura Bagby, 6 Degrees