Mar 30 2009
Ablynx [Euronext Brussels: ABLX], a pioneer in the discovery and development of Nanobodies®, a novel class of antibody-derived therapeutic proteins, announced today the detailed results from the Phase Ib study of its anti-thrombotic ALX-0081. The primary endpoint, demonstrating the complete inhibition of the target protein as measured by a specific biomarker, was reached in December 2008. These positive detailed data support the progression of ALX-0081 into Phase II testing, expected to commence in Q3 2009.
During the period May to December 2008, the study recruited a total of 25 patients with stable angina undergoing an elective percutaneous coronary intervention (PCI) procedure. Total daily doses of ALX-0081 ranging from 2 to 18 mg were added to a standard anti-thrombotic regimen including aspirin, heparin and Plavix®. The double blind study randomized patients in a 3:1 ratio to either active study drug (ALX-0081) or placebo, resulting in a total of 19 patients receiving ALX-0081 intravenous infusions and six patients receiving placebo. The biological effect of ALX-0081 was determined via a biomarker, indicating the complete inhibition of von Willebrand Factor (vWF) and its mediated effect on platelet aggregation and clotting in coronary arteries.
The study included a single dose and a multiple dose escalation. Single doses were escalated until the required biological effect (complete biomarker inhibition for at least six hours in all ALX-0081 treated patients) was confirmed. The subsequent multiple dosing was aimed to ensure complete inhibition of the biomarker for at least 24 hours. All patients who received ALX-0081 showed complete inhibition of the biomarker with a duration of 4 to 18 hours in the single dose group and for at least 24 hours in the multiple dose group. In all patients, the pharmacological markers returned to normal 12-36 hours after dosing.
The study treatment was safe and well tolerated. There were no apparent clinical differences in the number of patients with adverse events and in the intensity of these adverse events between the placebo group and the ALX-0081 treatment groups. Importantly, the treatment with ALX-0081 was not associated with any clinical signs of bleeding. Neither the single nor the multiple dose treatment resulted in detectable immunogenicity and no human anti-vWF antibody responses were detected during the 30 day follow up after the last injection, suggesting inherently low immunogenicity of the drug.
The pharmacological profile of ALX-0081 in this Phase Ib study confirmed the findings of the Phase Ia study in healthy volunteers, with a vWF adopted plasma half-life of 27 hours in the single ascending dose. The pharmacodynamic profile of the multiple dosing resulted in effective drug concentrations that correlate with the favorable pharmacodynamic effect (inhibition of biomarker) and did not result in adverse findings in the pharmacodynamic profile, i.e. no signs of drug accumulation were detected. The resulting pharmacokinetic and pharmacodynamic profiles of the four sequential administrations of ALX-0081 support the progression into Phase II testing.
In order to gain additional information on optimal dosing and scheduling in preparation for a Phase II trial, Ablynx has extended its Phase Ib study to look in more detail at biological markers, optimization of concurrent treatment with the standard anti-thrombotic regimen, tolerance and administration.
Edwin Moses, CEO and Chairman commented: “We are delighted with the rapid progress made to date and these positive Phase Ib results for ALX-0081 mean that we expect to proceed to a multi-centre Phase II study in PCI patients. The positive detailed analysis of our Phase Ib clinical trial is a significant milestone for Ablynx and represents a major step towards the potential development of an improved treatment option for PCI patients. We look forward to a positive outcome from our discussions with the regulatory authorities which should lead to initiation of the Phase II study in the third quarter of this year.”
Ablynx continues to advance its development portfolio. ALX-0681, which also targets vWF but is administered subcutaneously rather than intravenously, entered a healthy volunteer study in December 2008 and Ablynx expects to announce the final results of this Phase I study before the end of the third quarter of this year. By the end of 2009, Ablynx also aims to start a Phase I study for ALX-0141, which targets RANKL, an important target in osteoporosis.