New data presented at the American Thoracic Society’s 2004 International Conference show that once-daily treatment with the investigational therapy Alvesco (ciclesonide) in mild-to-moderate asthma patients has no effect on normal adrenal function, as demonstrated by measurements of the hypothalamic-pituitary-adrenal (HPA)-axis.
The HPA-axis is a major part of the neuroendocrine system, involving the interactions of the hypothalamus, the pituitary gland and the adrenal glands. The HPA-axis is believed to be a focus of the body's reactions to stress and is recognized as a surrogate marker for common adverse effects associated with the body’s reaction to extra cortisol production, as seen with steroid treatment.
Alvesco is an inhaled corticosteroid with novel release and distribution properties resulting in lung-targeted anti-inflammatory effects. Inhaled corticosteroids, considered to be the foundation of asthma treatment, work by reducing inflammation – the underlying disease process – in the lungs and airways.
“In this study, ciclesonide has shown no identifiable effects on the normal cortisol system. This indicates that the drug may have no detectable effects on the adrenal glands”, said Edward M. Kerwin, MD, medical director, Clinical Research Institute of Southern Oregon and lead investigator of the study.
Effects of ciclesonide on the HPA-axis were investigated in two identical Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Mild-to-moderate persistent asthma patients (n=1,015) twelve years and older received 80, 160 or 320mcg of ciclesonide, or placebo, once-daily in the morning for
12 weeks. HPA-axis function was assessed at baseline and at week 12 by determining peak serum cortisol levels stimulated by 1 mcg cosyntropin. Additionally, 24-hour urinary cortisol levels corrected for creatinine were assessed.
Results of the two studies showed that no significant differences were observed from baseline to week 12 in cosyntropin-stimulated peak serum cortisol (mcg /dL) levels (PBO: +0.49; CIC80: +0.22; CIC160: +1.51; CIC 320: +0.38), or 24-hour urinary cortisol levels corrected for creatinine (mcg /mg) for ciclesonide versus placebo (PBO: +0.0009; CIC80: -0.0013; CIC160: +0.0033; CIC 320: +0.0001).
In another analysis presented at the Conference, adverse events affecting the throat (oropharynx) were pooled from 4,260 patients who received ciclesonide in clinical trials, and compared with 1,652 patients who received other inhaled asthma medications (budesonide, beclomethasone dipropionate or fluticasone proprionate), and 934 patients who received placebo.
The ciclesonide patients experienced a lower incidence of oral candidiasis (fungal infection) than the placebo control group, and potential local adverse events rates were dose-independent and comparable to placebo.
“These findings underscore the benefits of ciclesonide’s novel release and distribution properties and suggest that ciclesonide exerts its effects in the airways, while minimizing risk elsewhere in the body,” noted Professor Heinz-Werner Radtke, Head of research and development at ALTANA Pharma. “The low incidence of local side effects we see with ciclesonide is promising news for patients and their physicians.”
Asthma is a chronic lung disease caused by airway inflammation and results in airway constriction in response to certain stimuli. It is characterized by a variety of symptoms including wheezing, coughing and a tightening of the airways, which causes shortness of breath and can be life-threatening. According to the Global Initiative for Asthma (GINA), more than 300 million people worldwide suffer from asthma. The prevalence of asthma is increasing by approximately 50 percent every decade and worldwide deaths from asthma total more than 180,000 annually.
In clinical trials, Alvesco was shown to improve lung function, asthma symptoms, and reduce the need for medications necessary to treat acute asthma attacks. The most frequently reported adverse events seen in Alvesco clinical trials were nasopharyngitis, headache and upper respiratory tract infection. Alvesco was approved in Australia and the United Kingdom this year, and has been submitted for approval in other countries around the world. Additionally, ALTANA’s U.S. partner, Aventis, applied to the FDA for approval of the asthma drug Alvesco at the end of 2003. Teijin, ALTANA’s partner in Japan, submitted an application for approval for Alvesco in January 2004. http://www.altana.de