Ablynx, a biopharmaceutical company, has started two additional phase I studies with its anti-RSV Nanobody, ALX-0171, with the goal of commencing paediatric development during the second half of 2014. Respiratory Syncytial Virus (RSV) is a respiratory virus that infects the lungs and respiratory tract and is the most common cause of bronchiolitis and pneumonia in children under one year of age.
The additional phase I studies are being performed to determine the appropriate dosing regimen in the subsequent paediatric development of the Nanobody, and will include a safety study in adults with hyper-responsive airways and a local and systemic pharmacokinetic (PK) study in healthy volunteers. The results of both phase I studies are expected during the first half of 2014.
Bronchoconstriction (narrowing of the airways in the lungs) induced by ALX-0171 inhalation has not been observed in healthy adult volunteers. A phase I study in adults with hyper-responsive airways will further evaluate the potential occurrence of bronchoconstriction following single escalating doses of ALX-0171 as well as repeated inhalation of ALX-0171. If indicated, the prevention or reversion of bronchoconstriction, involving the administration of a standard bronchodilator already often used in the management of RSV infection, will be assessed as well. This single-centre, open-label study is expected to recruit 24 subjects.
In addition, Ablynx has initiated a phase I study in healthy male volunteers to assess the local and systemic pharmacokinetics of single and repeated daily inhalations of ALX-0171, and the systemic pharmacokinetics of a single intravenous (iv) injection of ALX-0171. This Phase I study is expected to recruit 41 subjects and will examine doses of 0.3 mg/kg (iv) and fixed doses of 200 mg (inhalation).
Dr Edwin Moses, Chairman and CEO of Ablynx, commented, "We are very pleased to move forward with our first inhaled Nanobody, which has the potential to become a first-in-class therapeutic to treat RSV infection in young children, an area with high unmet medical need. These additional studies will provide us with an appropriate clinical package for ALX-0171 that should allow the start of a phase II study in infants during the second half of 2014."
Ablynx's innovative technology platform, which enables unique and flexible drug formatting, resulted in the creation of a trivalent Nanobody, ALX-0171. The physical robustness allows fast delivery directly into the lungs, i.e. the site of infection, via nebulisation. The trivalent structure allows for increased activity at the target, which enables neutralisation of virus replication in the lungs. As such, Ablynx was able to generate a therapeutic product that works specifically at the site of infection. In contrast, it is very difficult to nebulise classical monoclonal antibodies. As a result, these can currently only be administered systemically and it has proved very difficult to deliver sufficient antibody to the infection site to achieve a therapeutic effect. A phase I safety study in healthy male volunteers demonstrated that single and multiple inhalations of the Nanobody were well tolerated and no dose-limiting toxicity or treatment emergent immunogenicity was observed. Furthermore, ALX-0171 had no clinically relevant effect on lung function, no signs of bronchoconstriction were observed, and the Nanobody had the opportunity for once-daily dosing.
RSV remains the primary reason for infant hospitalisation and virus associated deaths in infants, hence the high need for an effective and specific anti-RSV therapeutic drug. It is estimated that there are more than 300,000 child hospitalisations per year in the seven major pharmaceutical markets and the reported infection rate is 70-80 per cent in children under two years of age. In addition, RSV infection is a significant cause of pulmonary disease in transplant patients, immune-compromised subjects and the elderly. Current treatment of patients infected with RSV is mostly symptomatic.
Ablynx is a biopharmaceutical company engaged in the discovery and development of Nanobodies, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious human diseases, including inflammation, haematology, oncology and pulmonary disease.