How Oral Octreotide Capsules Replace Monthly Injections for Acromegaly | Research

The takeaway

The TPE technology enables oral delivery of octreotide for acromegaly, achieving therapeutic levels despite only 0.7% oral bioavailability, offering patients a convenient alternative to monthly depot injections.

0.7% oral bioavailability
Still sufficient for therapeutic efficacy in Phase III trials, requiring 200x the injectable dose

What the researchers found

Oral octreotide using TPE technology achieved therapeutic endpoints in Phase III trials with ~0.7% relative oral bioavailability, requiring 20 mg capsules compared to 0.1 mg subcutaneous injections.

Why it matters

Successfully delivering a peptide drug orally is a major pharmaceutical achievement. This technology demonstrates that even with very low oral bioavailability, convenient oral peptide formulations can be clinically viable, opening doors for other peptide drugs.

The numbers in context

20 mg capsule; 0.7% bioavailability; 200x subcutaneous dose; 2 Phase III trials; FDA approved 2020

How the study worked

Technological evaluation reviewing the TPE platform, preclinical data, Phase I pharmacokinetics, and Phase III clinical trial results for oral octreotide (MYCAPSSA).

Who was studied

Acromegaly patients (review of clinical trial populations)

What this study cannot tell us

Very low oral bioavailability (0.7%) means most of the drug is not absorbed. Requires high oral doses. The technology may not be applicable to all peptides. Patient adherence to twice-daily dosing versus monthly injections has trade-offs.

How to read the evidence

Technological review of an FDA-approved product with Phase III clinical trial support. High-quality evidence for the specific application.

When this study was published

Published in 2021, shortly after FDA approval of MYCAPSSA in 2020.

The bigger picture

The oral delivery of peptide drugs has been a holy grail of pharmaceutical science. Following oral semaglutide for diabetes (2019), oral octreotide for acromegaly (2020) represents the second major milestone proving that selected peptides can be made orally available with the right formulation technology.

Questions still open

Could TPE technology be applied to deliver other therapeutic peptides orally?
How does long-term oral octreotide compare to injectable formulations in real-world outcomes?
Can formulation improvements increase the oral bioavailability beyond 0.7%?

Common questions

How can a peptide drug be taken as a pill?

The TPE (Transient Permeation Enhancer) technology uses an oily formulation with special excipients that temporarily open the tight junctions between intestinal cells, allowing the octreotide peptide to pass through into the bloodstream. Only about 0.7% gets absorbed, so the oral dose is much higher than the injectable version.

Is oral octreotide as effective as the injectable version?

Phase III clinical trials showed that oral octreotide capsules met the same primary efficacy endpoints as injectable formulations for controlling acromegaly. Many patients prefer the convenience of twice-daily pills over monthly depot injections.

Read the original research

Transient Permeation Enhancer® (TPE®) technology for oral delivery of octreotide: a technological evaluation.

Expert opinion on drug delivery, 18(10), 1501-1512

View on PubMed ↗Publisher’s paper ↗

Citation

Brayden, David J; Maher, Sam. (2021). Transient Permeation Enhancer® (TPE®) technology for oral delivery of octreotide: a technological evaluation.. Expert opinion on drug delivery, 18(10), 1501-1512. https://doi.org/10.1080/17425247.2021.1942838