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Pasireotide (SOM230) Shows Promise for Treating Acromegaly, Cushing's Disease and Carcinoid Tumors: Presented at AACE

By Mike Fillon

CHICAGO, I.L. -- May 2, 2006 -- Preliminary data from phase 2 clinical trials support the rationale for using pasireotide as a treatment for patients with acromegaly, Cushing's disease and metastatic carcinoid tumors.

Results of the study were presented here on April 27^th at the annual meeting of the American Association of Clinical Endocrinologists (AACE).

According to clinical researcher Allen Reha, PhD, from Novartis Pharmaceuticals Corp., pasireotide (SOM 230) is a novel, multi-ligand somatostatin analogue that exhibits high binding affinity to 4 of the 5 somatostatin receptor subtypes sst 1,2,3 and sst 5, potentially offering therapeutic benefits in conditions where these sst receptors are important, such as gastroentero-pancreatic neuroendocrine tumors, acromegaly and Cushing's disease.

In earlier phase 1 studies in healthy volunteers, pasireotide was evaluated in single or multiple doses up to 1500 mcg sc per day, and via continuous infusion at doses up to 2250 mcg sc per day. Pasireotide was well tolerated even at high doses with generally mild adverse events.

"Early data from phase 2 studies in metastatic carcinoid tumors resistant/refractory to Sandostatin LAR [octreotide injection], acromegaly, and Cushing's disease are promising for the novel pasireotide," Dr. Reha said.

Results so far from the Ongoing Phase II Clinical Program are as follows:

Acromegaly:
An ongoing, open-label, randomized, crossover study is assessing the safety and efficacy of pasireotide in patients with de novo or persistent/recurrent acromegaly, which is excessive growth due to the production of excessive growth hormone by the pituitary gland that most commonly occurs in middle-aged men and women.

Initial treatment for 28 days with octreotide 100 mcg sc twice daily was followed by pasireotide 200, 400 and 600 mcg sc bid for 28 days each (for a total study period of 16 weeks). Endpoints were mean growth hormone </=2.5 mcg/L and normalized IGF-1 levels for age/gender-matched controls.

Cushing's Disease:
Patients with de novo or persistent/recurrent Cushing's disease have been recruited into an ongoing, open-label, single-arm study. Each patient received pasireotide 600 mcg sc bid for 15 consecutive days.

Normalization of urinary free cortisol (UFC) was the primary efficacy measurement assessed by the mean of two 24-hour UFC collections, at baseline and after 15 days' treatment.

Metastatic Carcinoid Tumors:
A study is ongoing in patients with carcinoid tumors of the digestive system. Those enrolled were required to have symptoms of carcinoid syndrome with diarrhea and/or flushing, considered refractory/resistant to octreotide LAR. This was defined as a mean of >/= 4 bowel movements per day, and/or >/= 2 episodes of flushing per day over 15 day period.

Patients initially received pasireotide 300 mcg sc twice daily for 3 days; doses were escalated to a maximum of 900 mcg sc twice daily until partial or complete symptom control. Dose increases up to 1200 mcg sc twice were also approved for some patients based on evidence of therapeutic benefit.

Dr. Reha said preclinical evaluation of pasireotide has demonstrated significant inhibition of growth hormone and insulin-like growth factor-1 release suggesting efficacy for the treatment of acromegaly and neuroendocrine tumors. Also, effective inhibition of the release of adrenocorticotropic hormone suggests potential efficacy in the treatment of Cushing's disease.

"Evidence of the clinical efficacy and tolerability of pasireotide in all 3 indications -- acromegaly, Cushing's disease and metastatic carcinoid tumors -- continues to accumulate with the ongoing clinical development program," Dr. Reha said.


[Presentation title: Clinical Experience With Pasireotide (SOM230), the Novel Multi-Ligand Somatostatin Analogue. Abstract 294]

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