February 23, 2015

Chiasma issued results of a phase III study of octreotide in the treatment of adults with acromegaly. The open-label, dose-titration, single-arm, multi-center, baseline-controlled phase III trial enrolled 155 people diagnosed with acromegaly and managed on somatostatin analogs. During the dose-titration phase of the study, patients initially received 40mg (20mg BID) daily of octreotide capsules, which could be increased, as required, to 60mg/day or 80mg/day (two 40mg doses) to maintain clinical and biochemical response. The dose-titration phase was followed by a fixed-dose phase for up to seven months; at that point, patients could elect to continue into a voluntary six-month extension phase up to 13 months. The study found 89% of patients were either completely or partially responding to parenteral treatment at baseline. 65% of patients who received octreotide capsules twice a day achieved disease control, as measured by circulating concentrations of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations, at seven months (core treatment period), meeting the primary endpoint, and 62% achieved disease control at 13 months (end of treatment). 85% of responders, at the end of the dose-titration phase, had sustained response up to 13 months. 80% of patients who entered the fixed-dose phase improved or maintained their acromegaly symptoms (54% improved, 26% maintained), at the end of treatment. 89% percent of patients experienced an adverse event (AE); 92% of the events were mild to moderate. The most common AEs were reported in the gastrointestinal system, nervous system and musculoskeletal system, consistent with the known safety profile of octreotide and the disease burden of acromegaly, with no AEs related to the oral route of administration. The majority of the gastrointestinal AEs reported in the study were mild to moderate, occurring within the first two months of treatment and resolved on treatment (median duration 13 days). Based on these results, Chiasma intends

May 19, 2014

Novartis released results from a phase III trial of Signifor LAR (pasireotide LAR; SOM230) in patients with acromegaly. The multicenter, phase III study was a randomized, double-blind trial examining pasireotide LAR 40mg or pasireotide LAR 60mg v. continued open-label treatment with octreotide LAR 30mg or lanreotide Autogel 120mg (the control group) for 24 weeks. The trial included 198 patients with inadequately controlled acromegaly on maximum approved doses of octreotide LAR or lanreotide Autogel for at least six months, regardless of prior surgical status. IGF-1 normalization was achieved by 24.6% and 26.2% of patients taking pasireotide LAR 40mg and 60mg, respectively (95% CI, 14.836.9; P<0.001; 95% CI, 16.038.5; P<0.001), and was not achieved by any patients in the control arm (95% CI, 05.3). Additionally, 35.4% and 43.1% of patients in the pasireotide LAR 40mg and 60mg arms, respectively (95% CI, 23.948.2; 95% CI, 30.856.0), had mean GH levels of <2.5g/L compared to 13.2% in the control arm (95% CI, 6.223.6). Tumor size also was evaluated and the study found a greater proportion of patients receiving pasireotide LAR 40mg and 60mg achieved a greater than 25% decrease compared with those receiving octreotide LAR and lanreotide Autogel (18.5% [95% CI, 9.930.0] and 10.8% [95% CI, 4.420.9] v. 1.5% [95% CI, 07.9], respectively). The most common AEs associated with pasireotide LAR 40mg, 60mg and the control arm were hyperglycemia (33.3%, 30.6% and 13.6%), diabetes mellitus (20.6%, 25.8% and 7.6%) and diarrhea (15.9%, 19.4% and 4.5%), respectively. Worldwide regulatory filings for pasireotide LAR in acromegaly currently are underway.