Gilead Sciences Inc. disclosed positive data from the second Phase III trial of its inhaled antibiotic for patients with cystic fibrosis, and plans to file a new drug application for the product later this year.
Foster City, Calif.-based Gilead said the Phase III AIR-CF1 study of aztreonam lysine for inhalation for the treatment of CF patients who have pulmonary Pseudomonas aeruginosa infection met its primary efficacy endpoint of improved respiratory symptoms at day 28. The 164-patient, double-blind, randomized study also demonstrated a significant improvement vs. placebo at day 28 in respiratory function, a secondary endpoint.
Nathan Kaiser, manager of public affairs at Gilead, told BioWorld Today an NDA filing is expected in the second half of this year. He said the company would commercialize the product itself in the U.S.
The primary efficacy endpoint of improved respiratory symptoms from baseline was assessed by the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a patient-reported outcome (PRO) tool used to measure health-related quality of life for CF patients.
"The FDA, Cystic Fibrosis Foundation and medical community have identified PROs as important endpoints in clinical trials for CF and a variety of other diseases," Bruce Montgomery, senior vice president, head of respiratory therapeutics at Gilead, said in a news release. "AIR-CF1 is the first Phase III clinical trial in CF to use a PRO as its primary endpoint."
Gilead reported a mean change from baseline of 9.7 points (on a scale of 100) compared to placebo on patient-reported outcomes on respiratory symptoms (p<0.001). Aztreonam lysine-treated patients also experienced significant improvements in respiratory function, as measured by relative improvement of FEV1 (forced expiratory volume in one second), with a treatment difference in change from baseline of 10.3 percent vs. placebo (p< 0.001).
Kaiser said a number of other secondary endpoints also were measured related to respiratory function, hospitalization, use of other antibiotics, missed school and work days and others. Gilead was not disclosing data on those endpoints, but would at an upcoming scientific meeting when it plans to release full study results, he said.
Aztreonam lysine for inhalation, which had not yet been given a trade name, is a proprietary formulation of the antibiotic delivered by the eFlow Electronic Nebulizer developed by PARI Pharma GmbH. PARI, of Munich, Germany, contributed to the development and formulation of the product, although its stake in the drug going forward was not disclosed.
Gilead in December disclosed positive data from the first Phase III trial, the 247-patient AIR-CF2 study, which showed significant results on a different primary endpoint: the time to need for antibiotics after a 28-day treatment course. It was studied vs. placebo following a 28-day treatment course of tobramycin inhalation solution, or TOBI, an already-approved inhaled antibiotic for CF patients that Novartis AG acquired when it bought Chiron Corp.
Analysts at Jefferies & Co. Inc. said the Gilead news was "incrementally positive" but had no impact on its projections, given that the positive results were anticipated and the relatively small market size.
Jefferies in a research note projected market launch of aztreonam in the second half of 2008, with peak worldwide sales in 2012 of up to $250 million. Gilead's revenues in 2006 were slightly more $3 billion, primarily from sales of its HIV drugs.
Gilead acquired aztreonam last year through its purchase of Seattle-based Corus Pharma Inc. It invested $25 million in Corus in April 2006, and said three months later it was exercising its option to purchase all the company for $345 million. (See BioWorld Today, April 14, 2006, and July 21, 2006.)
Gilead has orphan status for aztreonam lysine for inhalation in both the U.S. and Europe, where it also has rights. An intravenous formulation of aztreonam already is approved by the FDA.
Jefferies said aztreonam for inhalation is well positioned for the "underserved" CF market, and to compete against TOBI. It said aztreonam potentially could be used as a monotherapy or add-on therapy to other antibiotics, including TOBI; that it potentially could be efficacious against TOBI-resistant infections, such as P. aeruginosa; and that delivery with the eFlow device is quicker than for TOBI, potentially three minutes vs. 15 to 20 minutes.
Sales of TOBI in 2005 were $233 million, Jefferies said.
Aztreonam is a monobactam antibiotic that inhibits bacterial cell wall synthesis. TOBI is an aminoglycoside antibiotic that inhibits bacterial protein synthesis.
The Phase III aztreonam program at Gilead also includes a third study, AIR-CF3, an ongoing open-label trial to evaluate longer-term safety, up to 18 months, in patients who participated in one of the two earlier studies.
Gilead described CF as a chronic, debilitating genetic disease in which a major characteristic is production of abnormally thick, sticky mucus in the lungs, trapping bacteria and predisposing patients to lung infections. Pulmonary infection with Gram-negative bacteria, particularly pulmonary P. aeruginosa, represents the single greatest cause of morbidity and mortality among CF patients, it said. There is no cure, and the goal of CF therapy is to control symptoms and prevent further lung damage.
A separate near-term event at Gilead is the June 18 targeted FDA review date on the NDA for ambrisentan, an endothelin receptor antagonist for treating pulmonary arterial hypertension.
Gilead's stock (NASDAQ:GILD) gained 31 cents Wednesday to close at $82.27.