The Novel, Ready-to-Use Octreotide Subcutaneous (sc) Depot Provides Higher Exposure and Maintains Response in Patients with Acromegaly and Functioning Neuroendocrine Tumors (NETs) Previously Treated with Long-Acting Octreotide: Results from a Phase 2, Open-Label, Multicenter, Randomized Study

Presentation Number: SUN 433
Date of Presentation: April 2nd, 2017

Diego Ferone1, Françoise Borson-Chazot2, Anne Cailleux3, Dieter Hörsch4, Harald Lahner5, Rosario Pivonello*6, Libuse Tauchmanova7, Christelle Darstein7, Håkan Olsson8, Fredrik Tiberg9 and Marianne Pavel10
1Endocrinology, DiMI, IRCCS AOU San Martino-IST, University of Genoa, Italy, 2Fédération d'Endocrinologie, Hospices Civils de Lyon and University Lyon1, France, 3CHU Rouen, Hôpital Charles Nicolle, 1 rue de Germont, 76031 Rouen cedex, France, 4Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors Bad Berka - ENETS Center of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany, 5Universitaetsklinikum Essen, Zentrum f. Innere Medizin, Essen, Germany, 6Università Federico II di Napoli, Naples, Italy, 7Novartis Pharma AG, Basel, Switzerland, 8Camurus AB, Lund, Sweden, 9Camurus AB, Lund, and Physical Chemistry, Lund University, Lund, Sweden, 10Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

Abstract

INTRODUCTION: Octreotide sc depot is a novel, ready-to-use formulation administered via a thin needle. In a phase 1 study in healthy volunteers, this sc depot provided greater bioavailability of octreotide with faster onset and stronger suppression of IGF-1 vs octreotide long-acting (oct long-acting). This phase 2 study evaluated the pharmacokinetics (PK), efficacy, and safety of octreotide sc depot in patients (pts) with acromegaly and functioning NETs, previously treated with oct long-acting.

METHODS: Adult pts with acromegaly or functioning, well-differentiated NETs treated for ≥2 months with oct long-acting (10/20/30 mg every 4 weeks [q4w]) received the last dose of oct long-acting treatment in study period 0 and were randomized 28 days later to receive octreotide sc depot 10 mg q2w, or 20 mg q4w for 3 months (period 1). Primary objective was to characterize the PK profile of octreotide sc depot after each injection vs PK for oct long-acting (period 0; reference period). Secondary objectives were to assess efficacy, safety, and tolerability of octreotide sc depot.

RESULTS: 12 pts were randomized to receive octreotide sc depot 10 mg q2w (acromegaly, n=3; NET, n=1) or 20 mg q4w (acromegaly, n=4; NET, n=4).

In acromegaly pts, steady state (SS) PK (for octreotide sc depot 10, 20 mg vs oct long-acting 10, 30 mg, respectively) – AUC0-28d (day*ng/L): 95.6, 78.5 vs 6.23, 24.1; Cmax (ng/mL): 10.6, 11.3 vs 0.35, 1.41. In NET pts, SS PK (for octreotide sc depot 10, 20 mg vs oct long-acting 20, 30 mg, respectively) – AUC0-28d (day*ng/L): 83.3, 135.0 vs 27.8, 39.9; Cmax (ng/mL): 5.61, 15.7 vs 1.68, 2.48.

Acromegaly group: 3 pts with IGF-1 < ULN at the end of period 0 maintained IGF-1 levels < ULN at the end of period 1; 2 pts with IGF-1 > ULN in period 0 improved their IGF-1 levels, though IGF-1 remained ULN at the end of period 1. At all time points, 4 pts had GH < 2.5µg/L while 1 pt had GH > 2.5 µg/L, with some fluctuations during periods 0 and 1 (2 pts not evaluated for efficacy).

NET group: No rescue therapy was needed during the study. In period 1, control of symptoms (bowel movements and flushing episodes) over time was similar, or improved vs period 0, whereas symptoms disappeared in 2 pts in the 20 mg group.

Adverse events (AEs) were reported in 6 (50%) and 8 (67%) pts during period 0 and 1, respectively; most common in period 1 were GI disorders. All AEs were of grade 1-2. Site injection pain of grade 1 was reported as AE in 2 pts with acromegaly on 20-mg octreotide sc depot.

CONCLUSION: The novel, ready-to-use octreotide sc depot provided higher exposure than oct long-acting in pts in both indications This study, though in a limited number of pts, showed that octreotide sc depot well maintained biochemical control in pts with acromegaly and symptom control in pts with functioning NETs. Octreotide sc depot was well tolerated, with a safety profile consistent with oct long-acting. A phase 3 study is planned to assess the long-term efficacy and safety.

 

Disclosure: DF: Advisory Group Member, Novartis Pharmaceuticals, Teacher, Novartis Pharmaceuticals, Study Investigator, Novartis Pharmaceuticals, Advisory Group Member, Ipsen, Study Investigator, Ipsen. FB: Advisory Group Member, Novartis Pharmaceuticals, Advisory Group Member, Ipsen, Advisory Group Member, Merck Serono, Consultant, Novo Nordisk, Speaker, Novo Nordisk, Advisory Group Member, Bayer, Inc., Speaker, Bayer, Inc., Speaker, HAC, Speaker, Genzyme Corporation, Advisory Group Member, Pfizer, Inc.. DH: Consultant, Lexicon Pharmaceuticals, Inc., Consultant, Ipsen, Consultant, Ipsen, Consultant, Novartis Pharmaceuticals, Consultant, Pfizer, Inc., Consultant, Pfizer, Inc.. HL: Consultant, Novartis Pharmaceuticals. RP: Study Investigator, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals, Clinical Researcher, Shire, Consultant, Shire, Speaker, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals, Speaker, Shire, Study Investigator, Ipsen, Study Investigator, Pfizer, Inc.. LT: Employee, Novartis Pharmaceuticals. CD: Employee, Novartis Pharmaceuticals. HO: Employee, Camurus. FT: Employee, Novartis Pharmaceuticals. Nothing to Disclose: AC, MP