Full Results Presented From Phase 1 Trial of PhaseBio's PB2452 Ticagrelor Reversal Agent
March 19, 2019—PhaseBio Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company, announced that results from the phase 1 clinical trial of PB2452, a novel reversal agent for the antiplatelet drug ticagrelor, were presented at the American College of Cardiology's 68th annual scientific session being held March 16–18 in New Orleans, Louisiana. Additionally, the results were published online by Deepak L. Bhatt, MD, et al in The New England Journal of Medicine.
The study demonstrated that PB2452 provided immediate and sustained reversal of ticagrelor antiplatelet effects without a report of drug-related serious adverse events, stated PhaseBio.
Dr. Bhatt commented in the company's announcement, “Patients taking ticagrelor to reduce the risk of a cardiac event are currently without an effective method to reverse its antiplatelet effects, which increases the risk of spontaneous major bleeding and can quickly produce life-threatening bleeding should they require emergency surgery. The results from the phase 1 trial demonstrate that intravenous PB2452 provided immediate and sustained reversal of ticagrelor antiplatelet activity, thereby potentially reducing the bleeding risk associated with ticagrelor. The data support further evaluation of PB2452 for the reversal of the antiplatelet effects of ticagrelor in emergency situations involving major bleeding and to enable emergent or urgent surgery in patients.”
PB2452 is a novel, recombinant, human monoclonal antibody antigen-binding fragment, or Fab fragment, designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations.
According to PhaseBio, the first-in-human, randomized, double-blind, placebo-controlled phase 1 clinical trial evaluated the safety, efficacy, and pharmacokinetics of intravenous PB2452 as a ticagrelor reversal agent in healthy volunteers. The study is composed of 64 volunteers aged 18 to 50 years who received either PB2452 or placebo.
Ten sequential cohorts evaluated doses of PB2452 ranging from 0.1 g to 18 g of PB2452.
- Cohorts 1 to 3 assessed doses of 0.1, 0.3, and 1.0 g of PB2452 infused for 30 minutes in the absence of ticagrelor pretreatment to assess initial safety
- Cohorts 4 to 6 received 30-minute infusions of 1.0, 3.0 and 9.0 g of PB2452 or placebo after ticagrelor pretreatment for 48 hours
- Cohorts 7 to 10 received an 18 g fixed dose of PB2452 or placebo through various infusion regimens
The investigators found that PB2452 demonstrated dose-linear increases in mean exposure across the dose range. Platelet function was assessed using light transmission aggregometry, a point-of-care P2Y12 platelet-reactivity test, and vasodilator-stimulated phosphoprotein assays.
They concluded that PB2452 reversed the antiplatelet effects of ticagrelor without a report of any drug-related serious adverse events, dose-limiting toxicities, or infusion-related reactions. The most frequently reported treatment-emergent adverse event was infusion-site bruising (8.3%). There were no adverse events leading to study drug discontinuation or hospitalization, reported the company.