Ambrilia Biopharma Inc. posted positive preliminary phase III results for its proprietary prolonged-release formulation of Octreotide (C2L) in acromegaly patients.

The primary objective of this study comparing C2L to Sandostatin LAR was met with both C2L and Sandostatin LAR, inducing a highly statistically significant decrease of Insulin-like Growth Factor 1 (IGF-1) (p less than 0.005 for both arms) and Growth Hormone (GH) (p less than 0.0001 for both arms) plasma levels. It was not possible to demonstrate non-inferiority, nor inferiority, of C2L over Sandostatin LAR. The company believes that it would have been difficult to reach this endpoint due to the small patient population and large initial differences in both IGF-1 and GH values. There were no dropouts during the study. No differences were observed between the two products in adverse events, which were mild and transient

"These preliminary data confirm that C2L is very effective at reducing GH, IGF-1 and clinical symptoms in acromegaly patients, with minimal side effects", said Professor Stafford Lightman, Professor of Medicine, University of Bristol and Henry-Wellcome Center for Integrative Neuroscience & Endocrinology (LINE), U.K., and principal investigator of the study.

Dr. Philippe Calais, president and chief executive officer, Ambrilia, said "I am encouraged by the preliminary results of this study. Accordingly, Ambrilia continues to pursue its planned clinical development programme for C2L and as previously announced, expects regulatory filings by its licensing partners to start during the second half of 2008".

This open label, multicenter, randomised, non-inferiority study compared the safety and efficacy of C2L to Sandostatin LAR in acromegalic patients. Sixty-five (65) patients with active acromegaly were randomized to receive either C2L 30 mg every six weeks (34 patients), or Sandostatin LAR 30 mg (Sandostatin) every four weeks (31 patients) for a period of 12 weeks (84 days). All patients completed the study. The primary objectives of the study were the reduction in IGF-1 and GH plasma levels, from baseline levels to the level on day 84.

C2L and Sandostatin both induced a statistically significant decrease of IGF-1 (p less than 0.005 for both arms) and GH plasma levels (p less than 0.0001 for both arms), at all time points throughout the study and at day 84. The mean percentage of GH decrease was similar in both groups throughout the study. IGF-1 response was also similar, though more pronounced in the Sandostatin group on day 84. The European authorities require statistical validation of IGF-1 levels whereas the US Food and Drug Administration requires descriptive statistics of GH levels.

The clinical efficacy of both products as measured by changes in signs and symptoms of acromegaly, acromegaly symptom scores and patient health status was also assessed as part of the study's secondary objectives. Improvement was marked and similar in both groups for all criteria.

The adverse events reported were minor and not unexpected, and their incidence and severity were similar in both groups. No patient withdrew from the trial due to the occurrence of adverse events, or for any other reason, despite the expected higher plateau observed in the pharmacokinetic profile of C2L.

In light of these results, the company moves forward with its planned clinical development of C2L. As some patients (14 of the 31 in the Sandostatin group, and 16 of the 34 in the C2L group), began to experience increasing GH plasma levels at the end of the treatment period, Ambrilia is evaluating the introduction of dose interval adjustments for those patients in the ongoing long term safety study designed as a continuation of the initial study, in which all 65 patients are currently receiving C2L. Furthermore, these dose interval adjustments will also be available for appropriate patients, in a separate study, which is currently being conducted in the U.S. and Europe. This study is designed to evaluate the safety and efficacy of 20 mg and 10 mg C2L doses in the same indication.

Ambrilia's product is a proprietary prolonged-release formulation of Octreotide. The original product is commercialised as Sandostatin LAR (octreotide acetate for injectable suspension, a registered trademark of Novartis Pharmaceuticals Corporation). Octreotide is used for the treatment of a rare disease called acromegaly caused by a tumour of the pituitary gland, and for certain rare digestive tumours.

Acromegaly is a serious chronic condition related to a permanent hypersecretion of Growth Hormone (GH) by the pituitary gland, generally of tumoral origin. This causes an excessive production of Insulin-like Growth Factor 1 (IGF-1), a hormone secreted from the liver and other tissues. Excessive production of IGF-1 and GH results in uncontrolled growth of various organs, and debilitating symptoms. Control of the GH and IGF-1 levels by Octreotide normalizes such excessive growth and symptoms. Appropriate treatment has been shown to improve quality of life and more importantly, to increase life expectancy, in patients with acromegaly. It is a life long treatment, with few, mild side effects.

Ambrilia Biopharma Inc. is a biopharmaceutical company dedicated to the discovery and development of novel treatments for viral diseases and cancer.