Pulmozyme

Pharmacotherapeutic group: respiratory system, ATC code: R 05 C B13. Mechanism of action Recombinant human DNase is a genetically engineered version of a naturally occurring human enzyme which cleaves extracellular DNA. Retention of viscous purulent secretions in the airways contributes both to reduced pulmonary function and to exacerbations of infection. Purulent secretions contain very high concentrations of extracellular DNA, a viscous polyanion released by degenerating leukocytes, which accumulate in response to infection. In vitro , dornase alfa hydrolyses DNA in sputum and greatly reduces the viscoelasticity of cystic fibrosis sputum. Clinical efficacy and safety Efficacy and safety was established in double-blind, placebo-controlled studies (Z0342/Z0343) in which patients over 5 years of age and with FVC over 40% predicted received 2.5 mg Pulmozyme once or twice daily over a 24-week period. Overall, 968 patients (mean age of 19 years) with a mean baseline FVC of 78% were randomised in these trials. Another placebo-controlled double-blind study (Z0713) evaluated the effect of Pulmozyme (2.5 mg once daily for 2 years) on pulmonary function in young patients (aged 6-11 years) with minimum evidence of lung disease as defined by FVC of ≥ 85% predicted. Overall, 474 patients (mean age of 8.4 years) with a mean baseline FVC of 102.3% were randomised in this trial. Results of the main endpoints are shown in the following tables. A significant increase in FEV 1 was observed in the beginning of treatment with Pulmozyme and subsided over time, especially after the first year of treatment; however, the difference with placebo remained statistically significant. Pulmozyme reduced the relative risk of respiratory tract exacerbations requiring parenteral antibiotics by about 30%; this reduction did not correlate with the improvement in FEV 1 measured during the first weeks of therapy. Studies Z0342/Z0343 Placebo 2.5mg QD 2.5mg BID N = 325 N = 322 N = 321 FEV 1 (% predicted) Mean % change from baseline Day 8 - 0.5% 7.9% 9.0% Week 24 0.1% 5.1% 3.6% Overall 0.0% 5.8% 5.6% p < 0.001 p < 0.001 % patients with exacerbations over 24 weeks 43% 34% 33% Relative risk (95% CI) 0.73 (0.57 - 0.94) 0.71 (0.55 - 0.91) p = 0.015 p = 0.007 Study Z0713 Placebo 2.5mg QD N = 235 N = 237 Spirometry Mean change from baseline (at Week 96) FEV 1 (% predicted) - 3.10 0.03 p = 0.008 FVC (% predicted) - 2.88 - 2.23 p = 0.54 FEF 25-75 (% predicted) - 4.05 3.83 p = 0.0008 % patients with exacerbations over 96 weeks 24% 17% Relative risk (95% CI) 0.66 (0.44 - 0.996) p = 0.048 Post-hoc analysis of the data suggests that the effects of Pulmozyme on respiratory tract exacerbations in older patients (>21 years) may be smaller than in younger patients, and that twice daily dosing may be required in the older patients. The percentage of older patients developing exacerbations over 24 weeks was 44% on placebo, 48% and 39% on Pulmozyme 2.5 mg daily and twice daily, respectively.