The project dealt with the development of inhalable and oral formulations of anakinra for the treatment of inflammation in cystic fibrosis (CF).

In a first step, a respirable dry powder of anakinra was obtained which demonstrated in vitro optimal properties in terms of preservation of the protein activity and stability over time at room temperature. In vivo studies on healthy and CF mice infected with typical pathogens, such as Aspergillus fumigatus or Pseudomonas aeruginosa, proved that single administration of the Anakinra dry powder, over a week of treatment, was more effective than daily Kineret or standard anakinra, at concentrations four times lower than the systemic dose. In addition, Anakinra administered via the pulmonary route was safer as it did not cause peripheral neutropenia, a known side effect of Kineret treatment, which is evident after repeated systemic administration. Pharmacokinetic studies have shown that this effect is also the result of a lower blood concentration of the protein when delivered to the lungs.

In the second phase of the project, an oral preparation of anakinra was obtained, with high stability when stored and in the gastric environment. In vivo studies on the same animal models confirmed the activity of the protein delivered through the oral route. Efficacy studies are still ongoing to confirm these observations.

Hence, both approaches show high potential. However, these results have to be confirmed in more advanced models of the disease. It should be noted that the preparations were designed to be industrially transferable to facilitate a rapid development process.

The results obtained with the inhaled formulation have been the subject of a patent application.