Friday, September 24, 2010

Promising Phase III results of pasireotide, a new therapy for Cushing’s disease

Novartis’ pasireotide effective in Cushing’s disease trial

The Swiss pharmaceutical company Novartis reported the results of a Phase III study of an experimental therapy pasireotide, also known as SOM230, which showed reduced cortisol levels in patients with Cushing’s disease. Pasireotide is first medical therapy to show efficacy in a Phase III trial in Cushing’s disease. Detailed results will be presented at the 14th Congress of the European Neuroendocrine Association (ENEA).

As the largest clinical trial in Cushing’s disease, PASPORT-CUSHINGS study was conducted at 68 sites in 18 countries involving 162 patients with persistent or recurrent Cushing’s disease, and in patients with newly diagnosed Cushing’s disease who are not suitable for surgery. The goals of the phase III trial are to evaluate the efficacy and safety of the experimental drug pasireotide.

The study showed that the majority of evaluable patients (91/103) experienced a reduction from baseline in urinary free cortisol (UFC) levels at six months. The UFC levels, which are major biomarkers of biochemical control of the disease, were reduced to normal in 26% of patients randomized to pasireotide 900ug twice daily, meeting the primary endpoint of the study. Additionally, median UFC was reduced by 48% in both the 900ug and 600ug dose groups. After 12 months of treatment, results confirmed the durability of the effect. On average, as UFC levels were reduced, clinical symptoms of Cushing’s disease improved including reduction of blood pressure, total cholesterol, weight and body mass index (BMI).

The trial results gave Novartis’ development pipeline another boost, only a few days after the approval of its potential blockbuster drug Gilenya by FDA. The company said the trial will be basis for first regulatory filing planned by year end.

Cushing’s disease is caused by a benign tumor in the pituitary gland that secretes adrenocorticotropic hormone (ACTH), which triggers the adrenal glands to produce excess cortisol. Cushing’s disease can cause severe cardiovascular and metabolic-related illnesses or death. There are currently no approved medicines to treat Cushing’s disease.

“There is a critical need for a medical treatment for people with Cushing’s disease because currently available options, such as surgery or radiotherapy, are ultimately not effective for many of the patients who suffer from this debilitating disease,” said William H. Ludlam, MD, PhD, Director, Seattle Pituitary Center at the Swedish Neuroscience Institute in Seattle, WA. “The results of this study suggest that pasireotide may help patients achieve biochemical control of their Cushing’s disease and its symptoms by directly targeting the pituitary tumor that triggers excess cortisol production.”

Pasireotide is a metabolically stable cyclohexapeptide, which targets multiple subtypes of the receptor for somatostatin. Its highest affinity is to sst5, a receptor subtype frequently expressed by the pituitary tumors associated with Cushing’s disease. Pasireotide was assigned orphan drug designation for Cushing’s disease in Europe and the US.


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