The results of four clinical trials for the treatment of lung infections associated with cystic fibrosis (CF) were presented at last week’s [removed]North American Cystic Fibrosis Conference[/removed] in Baltimore.
Novartis Pharmaceuticals Corp, East Hanover, NJ, announced that analysis of data from 12,740 patients with CF and Pseudomonas aeruginosa lung infection showed that use of TOBI® (tobramycin inhalation solution, USP) was associated with a 21% reduction in mortality (p <0.001) in the following year. This reduction was especially apparent among patients who used TOBI every year compared to those who never used the treatment.
The Novartis study included patients aged 6 years and older with FEV1 predicted of 25-75% and four or more P. aeruginosa cultures, who were identified from the Cystic Fibrosis Foundation’s Patient Registry between 1996 and 2008. Patients were followed from the first year after 1998 in which they met these criteria until death, or until continuous data were no longer available. Reported use of TOBI was obtained from annual questionnaires.
Transave Inc, Monmouth Junction, NJ, reported positive clinical trial results for ARIKACE™ (liposomal amikacin for inhalation), an antibiotic entering Phase III development for the treatment of chronic lung infections due to P. aeruginosa in CF patients. The trial data indicates that ARIKACE demonstrated superior clinical benefit compared to placebo as measured by significant and sustained improvement in lung function and reduction in Pseudomonas density. This benefit was sustained over multiple cycles.
The ARIKACE trial enrolled 49 patients to receive ARIKACE 560 mg once daily via an eFlow® nebulizer system from PARI Pharma GmbH for 28 consecutive days, followed by 56-day off-treatment observation period for each cycle. FEV1 increased significantly among patients receiving 560 mg of ARIKACE, with a relative improvement from baseline in FEV1 of 8.4% (95% CI +4.7%, +12.0%; p ≤0.0001) at the end of the treatment during cycles one to five. More than three quarters of the improvement in lung function was sustained at the end of the 56-day off-treatment period during the five cycles (about 14 months) with a relative improvement from baseline in FEV1 of 6.5% (95% CI =2.5%, +10.4%; p=0.0018).
Gilead Sciences Inc, Foster City, Calif, announced results of its head-to-head Phase III clinical trial of Cayston® (aztreonam for inhalation solution) versus tobramycin inhalation solution (TIS) in CF patients with P. aeruginosa. The trial results showed that Cayston is effective across three treatment cycles in improving lung function and respiratory symptom scores. In addition, Cayston was associated with reductions in pulmonary exacerbations, including hospitalizations.
In the study, 268 patients were randomized to receive 28-day intermittent repeating courses of Cayston (75 mg 3 times daily) via the Altera® nebulizer system (PARI Pharma GmbH) or TIS (300 mg twice daily) via the PARI LC Plus® nebulizer over a 24-week treatment period. Approximately 85% of patients in the study had received at least three courses of inhaled tobramycin in the 12 months prior to randomization.
Patients receiving Cayston had an adjusted mean actual increase in FEV1 percent predicated from baseline over 6 months of 2.05% compared to 0.66% decrease for patients receiving TIS. Safety results were similar across both arms of the study, with lower incidence of cough in patients receiving Cayston.
Pharmaxis Ltd, Sydney, Australia, reported results of pooled data from its two large scale 6-month Phase III trials of Bronchitol (inhaled mannitol) in people with CF. The two studies, which had a similar design, included 643 patients from 11 countries.
Over the 26 weeks of the two studies, patients treated with Bronchitol had an average 7.3% improvement in FEV1 compared to baseline ( p <0.001) and a highly significant improvement compared to patients in the control group ( p <0.001). In the sub group of patients who were also on rhDNase, patients taking Bronchitol showed a 5.3% improvement from baseline ( p <0.001), that was again superior to the control group (p=0.020). In the subgroup of patients who were not on rhDNase, patients taking Bronchitol showed a 9.44% improvement from baseline ( p <0.001), that was also superior to the control group (p=0.009). The overall rate per annum reduction in exacerbations for patients on Bronchitol versus those on control was 25% (NS) and the number of patients experiencing an exacerbation was 29% lower for those taking Bronchitol (NS). This result was achieved in a well-treated patient population who overall had a very low rate of exacerbations in the study.