GHENT, Belgium – Ablynx [Euronext Brussels: ABLX] today announced the positive results from its double-blind, randomized, placebo-controlled, single and multiple dose Phase I study with ALX-0681, a subcutaneous formulation of its novel anti-thrombotic Nanobody® that selectively targets von Willebrand factor (vWF). The positive Phase I data support the progression of ALX-0681 towards Phase II testing in patients with thrombotic thrombocytopenic purpura (TTP), expected to commence in Q2 2010. The anti-vWF Nanobody® received orphan drug designation by the EMEA and the FDA for the treatment of TTP in May this year.
The Phase I study was designed to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeated subcutaneous administrations of ALX-0681. A total of 36 healthy volunteers were treated with either single subcutaneous doses of ALX-0681 ranging from 2mg to 16mg or daily 10 mg subcutaneous injections for 7 or 14 days.
All administrations of ALX-0681 were well tolerated and did not result in clinically significant adverse events. No signs of local intolerance or clinically significant bleeding events occurred and no evidence of immunogenicity was observed for 45 days after completion of treatment.
The desired biological effect, determined by complete inhibition of a biomarker, was achieved for more than 14 days with daily injections of 10mg of the anti-vWF Nanobody® confirming the biological efficacy of ALX-0681. The PD parameters for coagulation Factor VIII and vWF showed a fast and reversible decrease compared to pre-dose values, with normalisation between 24 and 72 hours after the last administration, depending on dose. The PK profile remained unchanged after multiple administrations, confirming the favourable pharmacological behaviour of ALX-0681.
ALX-0681 is being developed for the treatment of patients with TTP. It is also anticipated that the subcutaneous administration of ALX-0681 will provide access to additional patient populations suffering from unwanted blood-clot formation, such as those with acute coronary syndrome (ACS), which are not currently addressed by the intravenous administration of ALX-0081.