EU's CHMP reverses opinion on Gilead's inhaled aztreonam
This article was originally published in Scrip
Gilead Science's nebulised antibiotic formulation, Cayston (aztreonam lysine) received a positive opinion from the EU's CHMP last week, for short-term use in cystic fibrosis patients, after a re-examination.
Cayston was turned down by the CHMP earlier this year, but Gilead asked for a re-examination, focusing particularly on its role as a short-term treatment of chronic airway infections due to Pseudomonas aeruginosa (scripnews.com, March 23rd, 2009). In March, the CHMP said it was concerned about there being insufficient evidence of Cayston's long-term benefits after repeated courses of treatment in different age groups, its safety after long-term use, and the emergence of bacterial resistance.
The US FDA has also expressed reservations about Cayston, and has asked for an additional clinical study before an NDA can be submitted – Gilead has two clinical studies under way assessing the product in cystic fibrosis patients. But Cayston has been submitted for approval in Australia, Canada, Switzerland and Turkey. The product was acquired by Gilead when it bought the drug delivery company Corus Pharma in 2006.
only short-term use
In its appeal of the March CHMP decision, Gilead indicated that Cayston was only intended for short-term use. This was considered acceptable by the CHMP, which concluded that the risk of side-effects and the development of resistance were also acceptable when Cayston use was limited to four weeks.
The CHMP took advice from an expert group specialising in the treatment of cystic fibrosis, and found that there was a need for new antibiotics in patients with cystic fibrosis, in whom bacterial infections are often resistant to commonly used medicines by the time they reach adulthood.
Cayston has been recommended for a conditional marketing authorisation in the EU – more information is required in patients who take repeated four-week courses, both in adults and children.
The product will be marketed as a 75mg powder and solvent for use in a nebuliser, and is expected to be indicated for the suppressive therapy of chronic pulmonary infection caused by P aeruginosa in adults with cystic fibrosis. It uses PARI Pharma's Eflow handheld electronic nebuliser, which uses a vibrating perforated membrane to aerosolise liquid formulations.
Aztreonam was first developed by Squibb (now Bristol-Myers Squibb) as Azactam, a narrow-spectrum injectable beta-lactam antibiotic for Gram-negative bacterial infections. It is now marketed by Elan Pharmaceuticals in the US, and achieved sales there of $17 million in the first quarter of this year.
Gilead has developed the lysine salt because it is less irritating to the bronchial mucosa than the conventional arginine salt. Clinical trials have shown that a 28-day, three times daily course of treatment is associated with a clinically relevant improvement in pulmonary function in adult patients with cystic fibrosis. The most common side-effects were wheezing, cough, non-allergic bronchospasm, rash and pyrexia.
The company recently started a Phase II study of inhaled aztreonam lysine for use in patients with bronchiectasis. It also has an inhaled formulation of fosfomycin and tobramycin (GS 9310/11) in Phase II trial for bacterial infections associated with cystic fibrosis.