Positive Phase Ib clinical trial results for L-CsA, inhaled liposomal cyclosporine A for the prevention and treatment of bronchiolitis obliterans from PARI Pharma, Monterey, Calif, are reported in the Journal of Aerosol Medicine and Pulmonary Drug Delivery. In May, PARI received orphan drug designation from the US Food and Drug Administration (FDA) for L-CsA delivered through an investigational eFlow nebulizer system.
"PARI’s encouraging results show that it is feasible and well tolerated to deposit relevant amounts of L-CsA into transplanted lungs. This has the potential to prevent and treat bronchiolitis obliterans in a more efficient way compared to current oral standard treatment,” said Jürgen Behr, MD, head of the Division of Respiratory Disease at the Ludwig Maximilians University, Munich, Germany, in a press announcement from PARI. “Inhaled L-CsA has a favorable drug distribution to the target sites in the lung, which should lead to lower side effects than associated with systemic cyclosporine exposure."
PARI Pharma’s trial included 12 lung transplant recipients; five patients had double lung transplants, and seven patients had single lung transplants. Patients were given a single dose application of 10mg or 20mg of liposomal L-CsA. Deposition data showed a peripheral lung deposition of 2mg for a nominal, 10mg dose that was nebulized in less than ten minutes. According to PARI, once daily administration of a nominal dose of 10mg L-CsA with an investigational eFlow nebulizer system would give approximately 14 mg L-CsA/week. Mean values for C(max) and AUC(0-inf) were up to 20ng/mL and 110 h ng/mL, respectively. These results were significantly lower compared to oral therapy.
PARI pharma’s investigational eFlow nebulizer system uses eFlow technology to enable aerosolization of liquid medications through the use of a vibrating, perforated membrane that includes thousands of small holes that produce the aerosol mist. According to the company, the eFlow technology produces aerosols with a very high density of active drug, a precisely defined droplet size, and a high proportion of respirable droplets delivered in the shortest possible period of time.