Ablynx announced detailed results from the open label extension of the phase-Ib study of its anti-thrombotic, ALX-0081, in patients with stable angina undergoing percutaneous coronary intervention (PCI). The results support those of the original phase-I study with ALX-0081 and collectively provide proof-of-concept that ALX-0081 is safe and well tolerated and a potent inhibitor of platelet aggregation.
The study was designed to investigate the effect of ALX-0081, which inhibits von Willebrand Factor (vWF), on vWF-mediated clotting, measured using platelet aggregation biomarkers. Additional objectives were to gather additional data regarding safety and administration. The study recruited a total of 22 patients with stable angina undergoing elective PCI. All patients received standard anti-thrombotic therapy, including aspirin, heparin and Plavix in addition to ALX-0081 (20 patients; total dose 18mg) or placebo (two patients).
All 22 patients received four bolus injections (i.v.) of ALX-0081 or placebo every six hours over 24 hours. vWF-mediated platelet aggregation was measured via the biomarker RICO (ristocetin cofactor). All 20 patients who received ALX-0081 experienced complete RICO inhibition, that was statistically significant compared with placebo, (p<0.0001). ALX-0081 was safe and well tolerated and did not result in clinically relevant bleeding events. No evidence of anti-drug antibodies was detected up to 30 days after the last injection.
Professor Jozef Bartunek, (Aalst, Belgium) primary investigator of the phase-Ib study commented, “With the highly statistically significant inhibition of vWF, we have achieved proof-of-concept with the biomarker indicating ALX-0081 is a potent inhibitor of vWF-mediated clotting in patients with stable angina undergoing PCI.”
Edwin Moses, CEO and chairman at Ablynx, commented, “We are delighted to see further evidence of efficacy and safety for ALX-0081 in patients with cardiovascular disease. This is a novel target and ALX-0081 could become an important next generation thrombosis treatment. Ablynx recently initiated a phase-II study with ALX-0081 and we look forward to obtaining data from this study by the end of 2010.”
Ablynx continues to advance its development portfolio. ALX-0681, which also targets vWF and is administered subcutaneously rather than intravenously, concluded a successful phase-I study in August 2009. Earlier this month, Ablynx initiated a phase-I study for ALX-0141, which targets RANKL, an important target in osteoporosis. Including the phase-II trial being conducted by Pfizer with an anti TNFalpha Nanobody, there are now four Nanobody products in clinical development.
ALX-0681 and ALX-0081 are novel 'first-in-class' therapeutic Nanobodies targeting von Willebrand factor (vWF), a protein found in the blood that acts at a very early stage in the coagulation cascade, namely platelet adhesion, in contrast to currently available anti-platelet drugs which act only in the late stage of platelet aggregation.
Ablynx believes that ALX-0681 and ALX-0081 target a key opportunity in the anti-thrombotic market as they may provide a solution to the cardiologist’s current dilemma in acute coronary syndrome (ACS) which typically involves achieving a balance between the prevention of unwanted blood clots and potentially life-threatening bleeding complications.
Founded in 2001 in Ghent, Belgium, Ablynx is a biopharmaceutical company focused on the discovery and development of Nanobodies, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious and life-threatening human diseases.