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Oil and water equivalency
GHENT, Belgium—Ablynx today announced positive results from the Phase 1 trial to demonstrate bioequivalence between the liquid and lyophilized formulations of caplacizumab, Ablynx's anti-von Willebrand factor (anti- vWF) nanobody developed for the treatment of acquired TTP.
The liquid formulation has been used in clinical trials to date but the lyophilized form is more stable and can be stored and transported at 5 ºC, which is much more convenient than the liquid formulation, which has to be stored and shipped frozen. The lyophilized form will now be used in the forthcoming Phase 3 trial and would be the formulation of choice for commercialization.
The Phase 1 trial involved a single-centre, open-label, randomized, single dose cross-over study in 24 healthy male subjects to evaluate the bioequivalence and tolerability of liquid and reconstituted lyophilized formulations of caplacizumab administered subcutaneously. The bioequivalence criteria were based on the evaluation of the "area under the plasma concentration versus time curve (AUC)" and the "maximum observed plasma concentration (Cmax)."
The results from this study demonstrate that the lyophilized and liquid formulations of caplacizumab administered subcutaneously are bioequivalent based on the pharmacokinetic parameters as described above. In addition, both formulations were well tolerated and no treatment emergent serious adverse events were reported.
Dr. Edwin Moses, CEO of Ablynx, commented: "We are very pleased to show bioequivalence between the liquid and lyophilized formulations of caplacizumab, which is a very important milestone in the development of the product. We believe that this lyophilized form has a number of advantages and will allow for convenient self-administration in the home setting. We are on track to starting the Phase 3 study with this new lyophilized formulation in patients with acquired TTP in mid-2015."
Caplacizumab is a bivalent anti-vWF nanobody which is highly potent and selective. It received Orphan Drug Designation in the U.S. and EU in 2009 and could be the first drug specifically approved for the treatment of acquired TTP as an adjunct to plasma exchange and immuno-suppressants. Efficacy and safety were demonstrated for caplacizumab in a worldwide Phase 2 study in patients with acquired TTP, demonstrating that it could act as a protective agent in the acute phase of the disease, preventing microthrombi and having the potential to reduce morbidity due to organ damage as well as preventing exacerbations. In addition, in this Phase 2 study, caplacizumab was generally well-tolerated and had a manageable bleeding side-effect profile.
Von Willebrand factor (vWF) is a blood glycoprotein involved in hemostasis, a complex process that causes the bleeding process to stop. vWF's primary function is to bind to other proteins, including glycoprotein Ib, in the initiation of platelet adhesion. vWF is implicated in TTP where ultra-large, multimeric precursors of vWF (UL-vWF) are present in the blood of patients leading to unwanted blood clot formation. UL-vWF can readily bind platelets leading to the formation of characteristic string-like clots in small blood vessels. Caplacizumab inhibits platelet binding to UL-vWF and thus has the potential to prevent the formation of these string-like clots in the blood of patients with acquired TTP.
TTP is a rare disorder of the blood coagulation system that causes extensive microscopic thromboses in small blood vessels throughout the body. It is a potentially life-threatening disorder characterized by thrombocytopenia, hemolytic anemia and microvascular thrombosis causing variable degrees of tissue ischemia and infarction. TTP exists in two forms: a congenital and an acquired form, with the latter accounting for about 90 percent of the patients. There are currently no drugs specifically approved for the treatment of TTP. The standard of care for the acquired form of TTP is multiple daily plasma exchanges until confirmed platelet normalization which occurs when the patient's platelet count returns to normal. This treatment requires lengthy hospital stays and may be associated with clinical complications. Additionally, a significant number of patients will subsequently suffer either an exacerbation of the TTP episode or a later relapse after recovering from a first TTP episode. There are believed to be approximately 10,000 TTP-related events in the U.S. and top 15 European markets per year.
Ablynx is a biopharmaceutical company engaged in the development of Nanobodies®, proprietary therapeutic proteins based on single-domain antibody fragments, which combine the advantages of conventional antibody drugs with some of the features of small-molecule drugs. Ablynx is dedicated to creating new medicines which will make a real difference to society. Today, the company has more than 30 proprietary and partnered programs in development in therapeutic areas including inflammation, hematology, oncology and respiratory disease. The company has collaborations and significant partnerships with pharmaceutical companies including AbbVie, Boehringer Ingelheim, Merck & Co, Merck Serono and Novartis. The company is headquartered in Ghent, Belgium.