The Food and Drug Administration approved the first inhaled therapy for pulmonary arterial hypertension in December.
Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.
The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in patients with severe pulmonary hypertension. In nature, prostacyclin is a local hormone; intravenous introduction can result in systemic side effects and progressive tolerance, requiring more and more of the drug.
The randomized clinical trial reported for approval was conducted on 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6‐9 inhalations per day) was 19%, compared with 4% for the placebo group. The response rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.
Iloprost is dispensed in single‐use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Labeling indicated that iloprost should not be inhaled more than once every 2 hours, and the drug is not effective while a patient is sleeping. Vital signs should be monitored when initiating iloprost because of the risk of syncope.
Iloprost, though not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, which markets the drug in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA in August 2004.
Clinical trials are underway in the United States to examine its interaction with other drug treatments for PAH, as well as for its potential as a preventive agent for lung cancer in heavy smokers.