Gilead's inhalation candidate for cystic fibrosis, aztreonam lysine, demonstrated improvement in lung function, with a particularly high compliance rate of 95 percent, based on interim results of an ongoing Phase III trial designed to evaluate the long-term use of the drug.

The Foster City, Calif., company released 12-month data from the open label study June 12 during the European Cystic Fibrosis Conference June 13 in Prague.

The antibiotic currently is under review by FDA after Gilead filed the NDA on Nov. 16, 2007, seeking an indication of CF treatment in patients infected with pulmonary Pseudomonas aeruginosa. Pulmonary infection with the Gram negative bacteria and others represents the single greatest cause of morbidity and mortality in patients with CF.

FDA accepted the NDA for a standard review, setting a PDUFA date of Sept. 16. The inhalation version of the drug has orphan status.

Aztreonam lysine also is under review by regulatory authorities in Australia, Canada and the European Union, although the EU application seeks approval of a different formulation, 75 mg powder for nebulizer solution. Gilead filed the drug in the EU and Canada in March and in Australia Nov. 30.

The latest study, AIR-CF3, builds on research already conducted by Gilead in two other trials, AIR-CF1 and AIR-CF2, which evaluated short-term treatment of aztreonam over 28 days. The interim data from AIR-CF3 involved 120 patients who had reached 12 months of treatment, including six treatment courses (28 days on and 28 days off). The trial will follow patients for 18 months.

The positive long-term data, including the encouraging compliance results, suggests the drug potentially could be a best-in-class option for treating CF patients with the bacteria. The current standard of care is tobramycin (Novartis' Tobi ).

JP Morgan analyst Geoffrey Meacham called aztreonam lysine an underappreciated asset with best-in-class potential in a June 13 note, citing the high patient compliance rates seen in AIR-CF3 study.

"In AIR-CF3, compliance out to 12 months was an impressive 95 percent, compared with Tobi, (for) which physicians say long-term compliance is around 50 percent," Meacham wrote. "Couple this with the improvement in quality of life with aztreonam lysine (measured by Cystic Fibrosis Questionnaire-Revised), and we believe it has a best-in-class profile that could make it standard of care."

Meacham is predicting that sales of aztreonam lysine could surpass earlier estimates. The analyst previously has targeted revenues of the drug at $28 million, $88 million and $153 million in the years 2008, 2009 and 2010, respectively.

A look at the long-term results

In AIR-CF3, Gilead is studying a 75 mg dose of aztreonam lysine administered two or three times daily. The trial enrolled 274 patients who participated in the pivotal Phase III AIR-CF1 and AIR-CF2 studies, both of which met their primary endpoints, with participants remaining on their original dosing regimen (¹ Also see "Gilead Inhalation Antibiotic For Cystic Fibrosis Successful In Second Pivotal Trial" - Pink Sheet, 30 May, 2007.).

The interim analysis includes 120 patients who reached the12-month treatment point, 72 in the three times daily treatment arm and 48 in the twice-daily group.

Those in the three times daily group experienced mean FEV1 (Forced Expiratory Volume in One Second) improvement of 5.2 percent from baseline over 12 months, Gilead reported. In addition, a CFQ-R improvement of 4.2 points above baseline was seen. A reduction from baseline in the measure of P. aeruginosa bacteria present in the lungs also was reported. Further, no changes in the bacteria's sensitivity to aztreonam lysine were observed, Gilead said.

"Given the challenges of antibiotic resistance, there is a need for a number of inhaled antibiotics - working through different mechanisms of action - to treat pseudomonal infection in CF," European Cystic Fibrosis Society President Stuart Elborn said in a statement.

Gilead recently launched a European open-label, parallel group Phase III study (0110) testing its compound against tobramycin. The 200-patient trial has a primary efficacy endpoint of relative change in FEV1 score at day 28 from baseline.

Gilead acquired aztreonam lysine as part of its 2006 purchase of Corus Pharma for $365 million (² Also see "Gilead Acquisition Of Corus Adds Respiratory Disease Candidate" - Pink Sheet, 21 July, 2006.).

Phase II data on Transave's Arikace released

During the conference in Prague, Transave reported data on a similar compound in development for CF patients infected with P. aeruginosa, Arikace (liposomal amikacin for inhalation).

Both Gilead's and Transave's antibiotics are inhalation formulations delivered by the same device, PARI Pharma's eFlow Electronic Nebulizer .

The Monmouth Junction, N.J., biopharma announced that Arikace, its lead compound, administered once-daily for 28 days at 280 mg or 560 mg doses resulted in clinically significant improvement in lung function in a Phase II study in Europe. Completion of dosing was at 56 days, and sustained treatment effect occurred with the 560 mg dose (p=0.004) and the 280 mg dose (p=0.09) measured byFEV1.

-Joseph Haas (j.haas@elsevier.com)

Gilead’s Cystic Fibrosis Drug Looks Good Long-Term, Firm Reports

More from Archive

More from Pink Sheet