LONDON ¿ PPL Therapeutics plc, of Edinburgh, Scotland, has reported positive data from a Phase IIc trial of its lead product, alpha-1-antitrypsin, known as AAT, in the prevention of lung infections in cystic fibrosis patients. The company, which specializes in the production of therapeutic proteins in the milk of transgenic animals, said there was a reduction of 25 percent in all infections and of 50 percent in severe infections in patients who were treated with the highest dose of 250 milligrams per day.
While this improvement was seen as clinically relevant, it was not statistically significant. PPL is looking for a partner for the compound and Ron James, managing director, said, ¿Discussions with potential marketing partners for the product are continuing and the initial view of two potential partners of these trial results appears positive.¿
There was also a trend towards a benefit in lung function from the 250 milligrams-per-day dose, but the study was not big enough to demonstrate a statistically significant difference in lung function. AAT was well tolerated.
A total of 131 patients took part in the trial at 18 centers in the U.K. Patients were randomly assigned to one of four groups taking a once daily, nebulized dose of placebo or milligram doses of 62.5, 125, or 25 of AAT for six months.
Dose-related levels of AAT were detected in plasma, indicating that inhaled delivery is effective and may be an alternative delivery route to intravenous infusion. PPL said it had a meeting with the FDA in February to discuss inhaled delivery of AAT, and is now seeking to define suitable endpoints for a clinical trial.
AAT is the natural inhibitor of the enzyme elastase, a protease which is believed to be responsible for causing most of the damage to the lungs of cystic fibrosis patients. Elastase, which is released in response to lung infections to break up bacterial proteins, also has a strong affinity for elastin, the protein which provides the elasticity of lung tissue. Excess elastase causes progressive degradation of the lung tissue. n