EXTON, Pennsylvania, February 16, 2012 /PRNewswire/ --
- Improved Cortisol Exposure-Time Profile with Plenadren Associated with Improved Outcomes -
ViroPharma Incorporated today announced that data from the pivotal study for their orphan drug Plenadren(R) (hydrocortisone, modified release tablet) were published in the Journal of Clinical Endocrinology and Metabolism (JCEM), a leading scientific journal for endocrinology. Plenadren was recently granted European Marketing Authorization for treatment of adrenal insufficiency in adults.
The authors described results showing that the once daily dual-release tablet provided a more circadian-based serum cortisol profile, and that reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during once daily treatment, compared to treatment with immediate release hydrocortisone three times per day. In particular, the authors noted glucose metabolism improved in patients with concomitant diabetes mellitus. In addition, the preference of once daily versus three times per day treatment was assessed to be large or very large by 85 percent of patients at 12 weeks.
Professor Gudmundur Johannsson of the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden, and primary author of the publication, commented, "These data indicate that patients with Addison's Disease now have an important therapeutic option with once daily Plenadren. The time-exposure of Plenadren may be important in improving the outcome of patients suffering with adrenal insufficiency."
Replacement therapy for the treatment of the rare disease adrenal insufficiency has been available for more than 50 years. Oral hydrocortisone is the most widely used replacement therapy for treatment, but no formal studies of its efficacy and safety have been performed in patients suffering from adrenal insufficiency. The JCEM publication entitled, 'Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation,' described the data from the prospective study on glucocorticoid replacement therapy in adrenal insufficiency. The pivotal study was an open label, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers in 64 patients with primary adrenal insufficiency, also called Addison's disease. The trial compared the efficacy and safety of the same daily doses of once daily Plenadren with conventional immediate release hydrocortisone given three times per day (TID). The most commonly reported adverse events on Plenadren during the crossover phase of the study were nasopharyngitis, fatigue, gastroenteritis and influenza with infections reported in 43.8% of patients on Plenadren and 39.1% on TID treatment. Six serious adverse events were reported during Plenadren treatment and two during TID treatment, all caused by infectious disorders. No deaths occurred during the study and no withdrawals due to adverse events were reported. Fifty-nine of 64 randomized patients (92%) chose to continue into the extension phase of the study.
Patients with adrenal insufficiency are dependent on exogenous glucocorticoid replacement therapy, such as hydrocortisone. While standard formulations of hydrocortisone require multiple daily doses that result in sizeable variations in cortisol levels, Plenadren is a once daily dual-release oral glucocorticoid tablet with a release profile designed to more closely mimic the body's natural secretion pattern of cortisol. These differences may explain the reductions in body weight and blood pressure and the improved glucose metabolism observed with Plenadren.
On November 3, 2011, the European Commission (EC) granted European Marketing Authorization for Plenadren(R) (hydrocortisone, modified release tablet), an orphan drug for treatment of adrenal insufficiency in adults, which will bring these patients their first pharmaceutical innovation in over 50 years. ViroPharma anticipates commercial launch of Plenadren in the EU in the fourth quarter of 2012. A named patient program is currently available to patients in the EU, which ViroPharma expects to continue until commercial launch. Plenadren is not approved in the United States. However, it has received orphan drug designation status in the United States and has maintained orphan status in Europe upon approval.
Adrenal insufficiency, or AI, is a result of insufficient cortisol production by the adrenal glands. Primary AI is caused by impairment of the adrenal glands, most often due to Addison's disease, a destruction of the adrenal cortex by an autoimmune disease, and Congenital Adrenal Hyperplasia, a gene mutation affecting cortisol production. Secondary AI is a result of breakdown of the hypothalamic-pituitary-adrenal (HPA) axis, most often due to a hypothalamic-pituitary tumor. AI is associated with potentially severe morbidities, including gastrointestinal distress, weight loss, kidney failure, muscle weakness, severe fatigue, low blood pressure, and depression. If not treated, adrenal crisis may develop, which can be fatal if not properly treated.
Although glucocorticoid hormone replacement therapy for adrenal insufficiency has been available for decades, studies have recorded complications and comorbidities including premature death, impaired quality of life, increased cardiovascular risk, and decreased bone mineral density in treated patients, most likely because of lack of therapeutic options, and difficulties when using them to match the natural secretion pattern of cortisol.