Out-licensing

Phase III Clinical Development of Octreotide (C2L) for the Treatment of Acromegaly

Introduction/Background

Acromegaly is a rare and serious condition related to the hypersecretion of growth hormone by the pituitary gland, generally of tumoral origin. This causes an uncontrolled growth of organs, debilitating symptoms and a shorter life expectancy.

Pharmacotherapy with somatostatin analogues is one of the treatment options, a life-long treatment with a few and mild side effects. Novartis' Sandostatin® (octreotide) is the market leader and which efficacy is clearly established for treating acromegaly. The yearly treatment with the long-acting release (LAR) formulation of the product, which consists of intramuscular injections every 4 weeks, is costly. Difficult reconstitution prior to injection is also an issue.

Aims/Hypothesis

We are developing an improved formulation of Sandostatin®LAR.

Research

Ambrilia has developed an improved, proprietary prolonged release formulation of Octreotide (C2L) for which Phase III results have indicated its ability to replace Sandostatin LAR® with less frequent injections and non inferior efficacy, and comparable safety. C2L is easier to reconstitute and could be the first therapeutic alternative to Sandostatin®LAR.

The open label, multicentre, randomized study compared the safety and efficacy of C2L to Sandostatin LAR® (SLAR) in acromegalic patients. The primary objectives of the study were the reduction in IGF-1 and GH. Secondary objectives were safety and clinical efficacy of both products as measured by changes in signs and symptoms of acromegaly and patient health status. In the first phase of Study 301, patients with acromegaly were randomly allocated to either SLAR 30 mg every 4 weeks or C2L 30 mg every 6 weeks, for a period of 12 weeks (84 days). Both C2L and SLAR induced a highly statistically significant decrease of IGF-1 and GH plasma levels. In the second phase of the study, all 65 patients received C2L every 6 weeks for another 12 weeks. In the group of 34 patients who received C2L throughout the study, significant efficacy was maintained on day 168 (D168), on GH, IGF-1, and clinical symptoms of acromegaly. In the group of 31 patients who switched treatment after the first phase, analysis comparing IGF-1 and GH plasma levels show that C2L administered every 6 weeks is able to maintain an efficacy comparable to that of SLAR on both parameters. In this group, the total number of patients reaching normal values of GH and IGF-1 was maintained after C2L given every six weeks. For GH, 42% were normalized at D168 with C2L versus 33% with SLAR at D84. For IGF-1, 42% were normalized with C2L at D168 versus 45% at D84 with SLAR. Preliminary non-inferiority statistical analysis on both GH and IGF-1 supports the equivalent efficacy of C2L at D168 compared to SLAR's efficacy on D84. The results also show the absence of a "carry-over" effect, by which the initial treatment with SLAR would have benefited the patients even after 12 weeks of C2L treatment. In addition, the improvement of clinical symptoms of acromegaly is highly significant in both groups, and equivalent with C2L to that observed during the SLAR treatment period.

Side effects were mild and transient, becoming very rare during the second phase of treatment (only four patients out of 65 had mild adverse events during the last treatment period). 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.

Overall, the top-line analysis of the results supports the ability of C2L 30 mg given every 6 weeks to replace Sandostatin LAR® given every 4 weeks at the same dose.

The preliminary statistical analysis confirms its safety and efficacy in acromegaly patients, and its ability to replace Sandostatin LAR® with less frequent injections and non-inferior efficacy on Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1).

Conclusion

A prolonged release formulation of Octreotide (C2L) is currently undergoing Phase III Clinical trials.

Relevance/Opportunity

Ambrilia's C2L is available for licensing. For more information, please contact below.

Phase III