BOSTON — Phase 3 data from the PASPORT-CUSHINGS trial show significantly reduced cortisol levels and improved quality of life in patients with Cushing’s disease who were assigned to pasireotide.
The investigational somatostatin analogue (SOM230, Novartis) targets cortisol production in Cushing’s disease. Currently, there is no approved medical treatment for the disease; most patients undergo surgery or radiation therapy. Now, researchers said these latest data support the potential use of pasireotide “as the first specific pituitary-targeted treatment in this disorder.”
The randomized, double blind PASPORT CUSHINGS trial enrolled 162 patients with Cushing’s disease from 18 countries. The majority of patients (n=135) had persistent or recurrent Cushing’s disease after prior treatment; 27 had new-onset disease but were not eligible for surgery. Researchers randomly assigned patients to twice-daily pasireotide injections of 600 mcg or 900 mcg. The blinding treatment was lifted at 6 months or at 3 months if patients did not respond to therapy. Months 6 to 12 were open-label, and nonresponders received a higher dose, if needed. The primary endpoint was urinary free cortisol levels at 6 months without dose titration. Lack of response was demonstrated by increased levels of urinary free cortisol or a urinary free cortisol level more than two times the upper limit of normal. Annamaria Colao, MD, from University of Naples, presented data on 103 patients during an oral session.
Of the patients assigned to the 900-mcg dose, 26.3% achieved normal urinary free cortisol levels at 6 months and 25% maintained normal levels at 12 months. Nearly 15% of patients assigned to the 600-mcg dose met the primary endpoint at 6 months and 13.4% at 12 months. Most patients with uncontrolled disease could be identified within 2 months, based on urinary free cortisol levels, the researchers said. Reductions in serum and salivary cortisol levels and plasma ACTH were also observed.
As urinary free cortisol levels decreased, symptoms of Cushing’s disease improved, including significant reductions in body weight, blood pressure and LDL cholesterol. The researchers also noted improvements in quality of life.
“The safety profile of pasireotide is similar to that of other somatostatin analogues,” Colao and colleagues said. Adverse events included transient gastrointestinal comfort and hyperglycemic events (reported in 70%). Elevations in fasting blood glucose and HbA1c levels were seen soon after pasireotide initiation. Thirteen (8%) of patients had an adverse event of hypercortisolism that the researchers said was responsive to dose reduction.
Endocrine Today previously reported phase 2 data from the PASPORT CUSHINGS trial.
Disclosure: The research was supported by Novartis. Dr. Colao reports no relevant financial disclosures. Other researchers report relevant ties to Novartis, Ipsen, Otsuka, Pfizer and Corcept Pharmaceuticals.
For more information:
- Colao A. OR09-6. Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston.