Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734).
ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected.
Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4–70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication.
Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.
M. Fleseriu, Advances in the pharmacotherapy of patients with acromegaly. Discov. Med. 17(96), 329–338 (2014) PubMed
S. Melmed, New therapeutic agents for acromegaly. Nat. Rev. Endocrinol. 12(2), 90–98 (2016) PubMed
Signifor LAR (pasireotide) [package insert]. Novartis Pharmaceuticals Corporation, East Hanover, 2014
D. Cuevas-Ramos, M. Fleseriu, Pasireotide: a novel treatment for patients with acromegaly. Drug Des. Dev. Ther 10, 227–239 (2016)
European Medicines Agency: Summary of Product Characteristics: Signifor powder and solvent for suspension for injection. Camberley, United Kingdom: Novartis Europharm Limited (2016)
K.J. Moloney, J.U. Mercado, W.H. Ludlam, M.R. Mayberg, Pasireotide (SOM230): a novel pituitary-targeted medical therapy for the treatment of patients with Cushing’s disease. Expert Rev. Endocrinol. Metab. 7(5), 491–502 (2012) CrossRef
A. Colao, M.D. Bronstein, P. Freda, F. Gu, C.-C. Shen, M. Gadelha, M. Fleseriu, A.J. van der Lely, A.J. Farrall, K. Hermosillo Reséndiz, M. Ruffin, Y. Chen, M. Sheppard, On behalf of the Pasireotide C2305 Study Group: Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J. Clin. Endocrinol. Metab. 99(3), 791–799 (2014) CrossRefPubMedPubMedCentral
M.D. Bronstein, M. Fleseriu, S. Neggers, A. Colao, M. Sheppard, F. Gu, C.-C. Shen, M. Gadelha, A.J. Farrall, K. Hermosillo Reséndiz, M. Ruffin, Y. Chen, P. Freda, On behalf of the Pasireotide C2305 Study Group: Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, phase III study. BMC Endocr. Disord. 16, 16 (2016) CrossRefPubMedPubMedCentral
M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman, V. Pronin, G. Raverot, I. Shimon, K.K. Lievre, J. Fleck, M. Aout, A.M. Pedroncelli, A. Colao, On behalf of the Pasireotide C2402 Study Group: Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes. Endocrinol 2(11), 875–884 (2014) CrossRefPubMed
H.A. Schmid, T. Brue, A. Colao, M.R. Gadelha, I. Shimon, K. Kapur, A.M. Pedroncelli, M. Fleseriu, Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine 53(1), 210–219 (2016)
National Cancer Institute: Common Terminology Criteria for Adverse events (CTCAE). Version 4.0 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm (2010). Accessed 8 June 2016
PGX. InovoBiologic Inc. http://www.pgx.com (2016). Accessed 5 October 2016
M. Sheppard, M.D. Bronstein, P. Freda, O. Serri, L. De Marinis, L. Naves, L. Rozhinskaya, K. Hermosillo Reséndiz, M. Ruffin, Y. Chen, A. Colao, Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, phase III study. Pituitary 18(3), 385–394 (2015) CrossRefPubMed
A.M. Colao, F. Gu, M.R. Gadelha, et al., Metformin-based oral antidiabetic therapy proved effective in hyperglycaemia associated with pasireotide in patients with acromegaly. Poster presented at the 17th European Congress of Endocrinology, Dublin, 16–20 May 2015
F. Gu, S. Ravichandran, L. Tseng , A. Subramanian, Y. Chen, C. Schöfl, Management of pasireotide-induced hyperglycemia in patients with Cushing’s disease or acromegaly: study design of a randomized, open-label, phase IV trial. Poster presented at Endocrine Society’s 97th Annual Meeting & Expo, San Diego, 5–8 March 2015
S. Kasayama, M. Otsuki, M. Takagi, H. Saito, S. Sumitani, H. Kouhara, M. Koga, Y. Saitoh, T. Ohnishi, N. Arita, Impaired β-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin. Endocrinol. (Oxf) 52(5), 549–555 (2000) CrossRef
A. Luger, Hyperglycemia in pasireotide-treated patients with acromegaly and its treatment. Endocrine (2016). 10.1007/s12020-016-1029-z
- Safety and tolerability of pasireotide long-acting release in acromegaly—results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study
Eliza B. Geer
on behalf of the ACCESS Study Investigators
- Springer US
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II