Approval for the new indication sees the launch of a new presentation of Signifor containing a different salt of the active ingredient, pasireotide pamoate, supplied as powder and solvent for suspension for injection.
Signifor remains available as a solution for injection containing pasireotide as the diaspartate salt. This presentation is indicated for the treatment of Cushing's syndrome in adults for whom surgery is not an option or has failed and is administered by subcutaneous injection twice daily.
Licensing approval for the new indication was based on the results of two phase III studies involving over 550 patients with acromegaly.
The PAOLA study was a randomised, parallel-group, three-arm study comparing double-blind intramuscular pasireotide 40mg (n=65) or 60mg (n=65) with an open-label active control (intramuscular octreotide 30mg or deep subcutaneous lanreotide 120mg, n=68), all given monthly, in inadequately controlled patients treated with maximum indicated doses of octreotide or lanreotide for at least six months before randomisation.
The proportion of patients achieving biochemical control at week 24 (defined as mean GH levels <2.5 microgram/l and normalisation of sex- and age-adjusted IGF-1 level) was significantly higher in the pasireotide 40mg and 60mg groups than in the active control group (15.4% and 20.0%, respectively vs 0%, p=0.0006 and p<0.0001).
In the second study (C2305), 358 patients with acromegaly who had not received any prior medical treatment for their condition were randomised to receive pasireotide 40mg (n=176) or octreotide 20mg (n=182), both given monthly by intramuscular injection. Doses of both drugs could be increased for efficacy after three and six months up to a maximum of 60mg and 30mg, respectively.
A significantly greater proportion of patients in the pasireotide group achieved biochemical control at month 12 than in the octreotide group (31.3% vs 19.2%, p=0.007).
Patients who achieved biochemical control or who were deemed to be benefiting from treatment could continue into an extension phase with the study treatment to which they were initially randomised. At month 25, 48.6% of pasireotide patients and 45.7% of octreotide patients had achieved biochemical control.
Patients who did not respond to their initial treatment were able to enter a crossover phase, with 81 patients crossing over from octreotide to pasireotide and 38 from pasireotide to octreotide. After 12 months, 17.3% of patients in the pasireotide group had achieved biochemical control vs 0% of those in the octreotide group.
The adverse effects associated with pasireotide in the trials were consistent with those associated with the somatostatin analogue class, with the exception of hyperglycaemia which occurred to a higher degree and more frequently with pasireotide.