Date: 2012-05-07
Type of information:
phase: 3
Announcement: results
Company: Novartis (Switzerland)
Product: pasireotide (SOM230) long-acting release (LAR)
Action
mechanism: Pasireotide (SOM230) is an investigational multireceptor targeting somatostatin analog (SSA) that binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3 and 5). Pasireotide is approved in the EU as Signifor® for the treatment of adult patients with Cushing\'s disease for whom surgery is not an option or for whom surgery has failed. Additional regulatory submissions for pasireotide for the treatment of Cushing\'s disease are under way worldwide.
Disease: acromegaly
Therapeutic area: Hormonal diseases - Rare diseases - Endocrine diseases
Country:
Trial
details: This study, known as PASPORT-ACROMEGALY (PASireotide clinical trial PORTfolio - ACROMEGALY), is a randomized, double-blind, Phase III study evaluating the efficacy and safety of pasireotide LAR compared to the current standard medical therapy, octreotide LAR, in 358 patients with active acromegaly, who were de novo with a visible adenoma on MRI or medically-naïve (no previous medical therapy, but prior pituitary surgery). Patients were randomized to receive intramuscular injections of pasireotide LAR 40mg (n=176) or octreotide LAR 20mg (n=182) every 28 days for 12 months. At months three and seven, dose titration to pasireotide LAR 60mg or octreotide30mg was permitted if patients had GH >=2.5µg/L and/or IGF-1 > upper limit of normal (ULN). The primary endpoint was to compare the proportion of patients in the pasireotide LAR and octreotide LARtreatment arms with GH <2.5µg/L and normal IGF-1 at 12 months. Key secondary endpoints included comparison of the effect of pasireotide LAR and octreotide LAR on reduction of GH to <2.5µg/L alone and normalization of IGF-1 alone. Reductions of tumor volume, symptoms and prolactin levels were also assessed.
At the end of the 12-month study, eligible patients could enroll in an optional, double-blind, 6-month extension phase. In this phase of the study, patients that did not achieve full biochemical control could switch treatment at month 13 to either pasireotide LAR 40mg every 28 days (n=81) or octreotide LAR 20mg every 28 days (n=38), with dose titration allowed at 3-month intervals. Patients with GH <2.5µg/L and normal IGF-1 at month 12 could continue on their randomized therapy[5].
Latest
news: Results of the largest Phase III study of acromegaly patients show the novel therapy pasireotide (SOM230) long-acting release (LAR), was significantly more effective at inducing full biochemical control compared to the current standard medical therapy, Sandostatin® LAR® (octreotide/IM injection). These data were presented at the 2012 joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology meeting (ICE/ECE) in Florence, Italy.
The study met its primary endpoint, with significantly more patients treated with pasireotide LAR (31.3%) experiencing full control of their disease (defined as the combination of both GH <2.5µg/L and age- and sex-matched normalized IGF-1 levels) than those taking octreotide LAR (19.2%) (p=0.007). Patients treated with pasireotide LAR were 63% more likely to achieve control of their disease than those on octreotide LAR. The safety profile of pasireotide LAR was similar to that of octreotide LAR with the exception of a higher degree of hyperglycemia.
Growth hormone and IGF-1 levels are typically used to determine control of the disease with the most commonly used standard medical therapy, somatostatin analogs. Currently, only 20-25% of acromegaly patients naïve to previous somatostatin analog treatment achieve full control over their disease when treated with current somatostatin analogs, as measured by these two levels.
At baseline, mean GH was 21.9 µg/L and 18.8µg/L in the pasireotide LAR and octreotide LAR arms, respectively; mean IGF-1 was 2.6xULN and 2.8xULN. The primary endpoint was achieved by 31.3% of pasireotide LAR recipients and 19.2% of octreotide LAR recipients (p=0.007). Mean GH and IGF-1 decreased by month three and remained suppressed. At month 12, 48.3% of patients receiving pasireotide LAR had mean GH<2.5µg/L compared to 51.6% of those on octreotide LAR (p=0.536), while normal IGF-1 was achieved by 38.6% of patients receiving pasireotide LAR and 23.6% of patients receiving octreotide LAR (p=0.002). Additionally, investigators reported that both pasireotide LAR and octreotide LAR were effective in reducing GH levels and tumor volume, and improving health-related quality of life and signs/symptoms of the disease.
Most adverse events (AEs) were mild or moderate. The most common AEs reported by investigators with pasireotide LAR versus octreotide LAR were diarrhea (39.3% vs. 45%), cholelithiasis (25.8% vs. 35.6%), headache (18.5% vs. 26.1%) and hyperglycemia (28.7% vs. 8.3%).
