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Oral octreotide safe, effective as monotherapy for acromegaly in phase 3 trial
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An oral therapeutic peptide helped patients with acromegaly control insulin-like growth factor-1 and growth hormone for up to 13 months after they switched from injectable somatostatin receptor ligands, according to research published in the Journal of Clinical Endocrinology & Metabolism.
The oral octreotide capsules, which facilitate intestinal absorption of the drug through a transient permeability enhancer, also had a safety profile consistent with approved injectable somatostatin receptor ligands in the phase 3 trial.
“This novel [transient permeability enhancer] technology safely and successfully allowed oral delivery of a therapeutic peptide that achieved systemic endocrine effects,” the researchers wrote. “Twice daily [oral octreotide capsule therapy] appears to offer a safe option for acromegaly monotherapy.”
Shlomo Melmed, MD, of Cedars-Sinai Medical Center, Los Angeles, California, and colleagues from other institutions evaluated 151 completely or partially controlled patients with insulin-like growth factor-1 (IGF-1) less than 1.3 x the upper limit of normal and 2-hour integrated growth hormone (GH) less than 2.5 ng/mL.
The patients, who had received injectable somatostatin receptor ligands for at least 3 months, were switched to octreotide capsules (40 mg/day) with dose escalation (60 mg/day, then 80 mg/day) to control IGF-1. Subsequent fixed doses were continued over the core 7-month treatment, with a voluntary 6-month extension thereafter.
For the primary endpoint, the researchers looked for IGF-1 less than 1.3 x the upper limit of normal and mean integrated GH less than 2.5 ng/mL at the end of the core trial and the end of the extension; 65% reached these levels at 7 months and 62% at end of treatment.
The therapy demonstrated lasting effect, with 85% of patients initially controlled on oral octreotide maintaining response for up to 13 months. GH levels that were controlled on the octreotide capsules were reduced compared to baseline, and acromegaly-related symptoms improved.
Core treatment was completed by 102 patients, with 86% electing to enroll in the extension; 26 patients experienced treatment failure (IGF-1 ≥ 1.3 x ULN) and terminated the study early; 23 withdrew due to adverse events.
“In healthy volunteers, 20-mg [oral octreotide capsules] yielded systemic drug exposure comparable to a 0.1-mg subcutaneous dose of octreotide,” the researchers wrote. “We now show clinical utility and unique mode of action of [a transient permeability enhancer], whereby a therapeutic peptide is effectively and safely delivered orally.”
Disclosure: The study was sponsored by Chiasma, Inc. Melmed reports various financial ties with Chiasma, Inc., Novartis, Pfizer, Ipsen and Genentech. Please see the full study for a list of all other researchers’ financial disclosures.
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