Therapy Analysis - Asthma
Corticosteroid therapeutics
According to Pharmaprojects’ data, there are 91 drugs which have been launched since 1980, and are primarily indicated for the treatment of asthma (Graph 1). An R&D pipeline breakdown shows 54, 34, 45 and 6 in preclinical, Phase I, Phase II and Phase III development, respectively. Of the launched compounds, steroids make up 20% against 13% for long acting B2 agonists (LABAs). Ever since the discovery of cortisol, research and development has intensified to develop corticosteroids with improved therapeutic ratios and fewer systemic side-effects through better understanding of their multiple mechanisms of action.
Budesonide, marketed by AstraZeneca as Pulmicort, was a major success in tackling some of the notorious steroidrelated adverse events. In a 2 year Phase III trial in over 7,000 corticosteroid-naive patients aged 5-66 with mild, persistent asthma, budesonide-treated patients had a 44% lower risk of severe asthma-related events, 69% fewer hospital stays and a reduced need for corticosteroid use. Additionally, due to its high first-pass metabolism, budesonide is associated with fewer bone density losses and has little influence on the hypothalamic-pituitary-adrenal (HPA) axis, as opposed to, for example, prednisolone. Furthermore, AstraZeneca went on to develop Pulmicort Turbuhaler, which uses a simple-to-use delivery system that is inhalation driven, unlike aerosol inhalers that require CFCs.
More recently, ciclesonide was launched in 2004 by Nycomed Pharma. It has an improved therapeutic ratio compared to other corticosteroids as it is hydrolyzed to its active metabolite, desisobutyryl ciclesonide, in the lungs. In 2 double-blind Phase III trials in 1015 patients with mild-tomoderate asthma, ciclesonide was well tolerated, significantly improved quality of life and had similar incidence of oropharyngeal side-effects to placebo. HPA-axis function tests showed no significant differences from baseline in cortisol levels, cf placebo, for all dosages. 85.2% of ciclesonidetreated patients completed 12 weeks of treatment compared with 66.7% on placebo. In an additional 12-week doubleblind, randomized trial in 556 paediatric patients aged 6-15 with moderate-to-severe persistent asthma, ciclesonide via metered-dose inhaler was as effective as fluticasone propionate. Additionally, oropharyngeal related adverse events occurred with fluticasone-treated patients, but not in ciclesonide-treated patients.
