Aerovant is a recombinant form of human IL-4 that potently inhibits the cytokines IL-4 and IL-13, thereby dampening the inflammation that is common in both asthma and eczema. IL-4 is an upstream cytokine that regulates IgE production, and IL-13 acts similarly to IL-4.
In a Phase IIa antigen-challenge study in 30 patients, Aerovant reportedly reduced the severity of asthmatic attacks by 72% with twice-daily use for a month. Markers of airway inflammation such as forced expiratory nitric oxide also decreased.
In the past, patients received Aerovant through a cumbersome nebulizer. Now a more patient-friendly, dry powder formulation, packaged in a standard inhaler is available. This improved formulation is undergoing tolerability testing before starting a large Phase IIb study in the first quarter of 2008.
Aeroderm also potently binds IL-4 and IL-13 receptors. Eczema patients who received the compound in a Phase IIa trial improved their clinical status from severe to moderate, while the condition of controls remained severe, according to Aerovance. Aeroderm-treated participants also had fewer and less severe flare-ups of eczema, the company adds.
The volunteers, however, required two daily injections of Aeroderm, a dosing regimen that is not suitable for long-term treatment. A new pegylated formulation of Aeroderm will allow volunteers to receive just one injection weekly in future clinical studies.
Aerolytic and Pulmolytic are based on a truncated serine protease inhibitor. Both biologics interact with the enzyme prostasin to inhibit the epithelial sodium channel. Prostasin causes about 80% of the mucus production that plugs the lungs of CF patients, leading to congestion and lethal infections.
Rather than treating lung infections with antibiotics like tobramyacin, Aerolytic blocks the underlying production of mucus. “We want to hit the disease at the top of the pathological mechanism to have a more profound effect,” says Perry. A Phase IIa trial of Aerolytic administred by nebulizer is under way in Europe, and the results are expected by October.
Similar defects in epithelial sodium channels and prostasin are involved in COPD. Pulmolytic reportedly shows potential to normalize fluid abnormalities in the lungs of COPD patients and prevent disease progression. Pulmolytic has been investigated in a Phase IIa trial in COPD patients.