Endocrine Abstracts (2010) 22 P625

Efficacy and safety of co-administration of lanreotide Autogel 120 mg monthly with pegvisomant weekly in patients with acromegaly partially controlled by somatostatin analogues

Aart-Jan van der Lely1, Ignacio Bernabeu2, Jan Cap7, Philippe Caron3, Annamaria Colao4, Catherine Lesage5, Josef Marek5, Sebastian Neggers1 & Pascal Birman5

1Erasmus, Rotterdam, The Netherlands; 2Universitario de Santiago, La Coruna, Spain; 3CHU Rangueil, Toulouse, France; 4Federico II University of Naples, Napoli, Italy; 5Ipsen Innovation, Les Ulis, France; 61st School of Medicine Charles University, Prague, Czech Republic; 72nd Medical Clinic University Hospital Charles University, Hradec Kralove, Czech Republic.

Recent studies have shown that the co-administration of lanreotide (lan) with pegvisomant (peg) was able to normalise IGF1 secretion in patients with acromegaly who were partial responders to somatostatin analogues (SSAs).

Fifty seven subjects with acromegaly (mean age 51.6±12.7 years) not previously controlled by SSAs (either treated by SSAs for at least 6 months with IGF1 > ULN, or on peg for at least 3 months) with IGF1 > 1.2 ULN (n=54) or with IGF1 > ULN and GH nadir ≥ 1 μg/l (n=3) after a 4 month run-in period on lan 120 mg monthly entered into a co-administration period to evaluate the efficacy and safety of combining monthly injections of lan 120 mg with peg for 28 weeks. Peg starting dose of 60 mg once weekly could be progressively adapted every 8 weeks based on IGF1 levels from 40 to 80 mg once weekly up to 60 mg twice a week. Serum IGF1 was normalized at the end of the co-administration period in 33 (58%) subjects. The median weekly dose of peg taken by subjects who normalized IGF1 level was 60 mg. The percentage of subjects normalized was significantly higher in non diabetics (24/38=63% than in diabetic patients 9/19=47%). Older subjects were more likely to achieve normalisation than younger ones (odd ratio: 3.395 (P=0.03)). Serum IGF1 was normalised in 45 (79%) subjects at least once at any time during the co-administration period (P < 0.0001). Small mean improvements were seen in the quality of life scores, however these changes were associated with large data variability. Co-administration of lan and peg was well tolerated. Five subjects reported treatment emergent adverse events (AEs) leading to peg withdrawal: thrombocytopenia and urticaria were serious AEs considered drug-related while abdominal pain and vomiting was a serious AE considered non drug-related; the 2 other (non serious) TEAS were transaminases increase > 5× ULN which returned to normal after peg withdrawal. Altogether 6 (10.5%) subjects experienced transient increases of transaminases ≥ 2× ULN, not related to their diabetic status.

Co-administration of lan Autogel 120 mg monthly with peg weekly appears to be safe and to improve hormonal control in a majority of patients with acromegaly partially controlled by somatostatin analogues alone. When compared to the available data on peg monotherapy, co administration needs substantially less peg per week to achieve the same efficacy.