The industrial design, translation, and development strategies for long-acting peptide delivery

ABSTRACT

Introduction

Peptides are widely recognized as therapeutic agents in the treatment of a wide range of diseases, such as cancer and diabetes. However, their use has been limited by their short half-life, due to significant metabolism by exo- and endo-peptidases as well as their inherent poor physical and chemical stability. Research with the aim of improving their half-life in the body and thus improving patient compliance (by decreasing the frequency of injections) has gained significant attention.

Areas covered

This review outlines the current landscape and industrial approaches to achieve extended peptide exposure and reduce dosing frequency. Emphasis is placed on identifying challenges in drug product manufacturing and desirable critical quality attributes that are essential for activity and safety, providing insights into chemistry and design aspects impacting peptide release, and summarizing important considerations for CMC developability assessments of sustained release peptide drugs.

Expert opinion

Bring the patient and disease perspective early into development. Substantial advances have been made in the field of sustained delivery of peptides despite their complexity. The article will also highlight considerations for early-stage product design and development, providing an industrial perspective on risk mitigation in developing sustained release peptide drug products.

KEYWORDS:

• peptide delivery
• sustained release
• long acting injectable formulation
• half-life extension
• self-assembly
• PLGA microsphere/implant
• depot

Article highlights

• Peptides have emerged as one of the most important class of therapeutic drugs; however, their applicability as a suitable drug product has been limited by their short half-life. Therefore, it is important to exploit approaches to enhance the sustained release (SR) and prolong the exposure to achieve desirable biological effect.

• In this review, we outline the major formulation and delivery strategies that have achieved sustained peptide release and lead to successful launching of long acting injectable (LAI) marketed products.

• We also highlight the key challenges from pre-formulation screening to clinical manufacture, identifying the desired critical quality attributes for peptide SR pre-clinical formulations made from different approaches.

• We emphasize the challenges and opportunities in drug product design and strategies for mitigation particularly LAI’s, which includes syringeability and injectability, drug loading, drug release, burst effect, peptide stability and manufacturing complexity.

• Finally, we outline various elements of desired LAI peptide products and main risks in their development including cost of goods. We also refer the classical James Utterback innovation model for successful LAI product development.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.