A literature review of the patent application publications on cabotegravir – an HIV integrase strand transfer inhibitor

ABSTRACT

Introduction: Studies presented in the patent applications demonstrate that a new integrase strand transfer inhibitor cabotegravir might be used as long-acting antiretroviral formulation or delivery system that reduces dosing frequency and may therefore increase adherence and thus pre-exposure prophylaxis (PrEP) and treatment efficacy against HIV. As announced in 2019, the developer ViiV Healthcare seeks US and EU approval of long-acting, injectable HIV treatment.

Area covered: This review covers all the patent applications published until October 2019 with cabotegravir in the examples or claim section of the patent application document. The patent applications cover drug substance synthesis, solid-state forms, therapeutic applications, in vitro and in vivo efficacy as well as the potential formulations of cabotegravir alone or in combination with other anti-HIV agents.

Expert opinion: The results from multiple clinical studies suggest that cabotegravir can be used as PrEP agent and treatment agent against HIV. Multiple studies use cabotegravir in combination with other anti-HIV agents such as rilpivirine. Cabotegravir in combination with rilpivirine is an interesting therapeutic, due to the possibility of formulating long-acting formulation with dosing interval of every 4 weeks or less, thus reducing daily pill burden and improving patient’s compliance.

KEYWORDS:

• Integrase strand transfer inhibitor
• hiv therapy
• hiv prophylaxis
• cabotegravir

Article highlights

• Integrase strand transfer enzyme is HIV enzyme that allows HIV to integrate its genetic material into host’s genetic material, thus allowing HIV to use host’s replication systems.

• Cabotegravir is an investigational second-generation integrase strand transfer inhibitor for HIV treatment and pre-exposure prophylaxis (PrEP). It has a long systemic half-life (approximately 40 h after oral administration), high antiviral potency and low aqueous solubility, thus making it the perfect candidate for use as long-acting medication.

• It has already shown to be a useful therapeutic in recent clinical studies and the combination of cabotegravir and rilpivirine as long-acting formulation already seeks regulatory approval.

• Combinational treatment using cabotegravir has demonstrated a synergistic effect and has proven valuable in some examples of drug-resistant HIV mutants.

Acknowledgments

This document does not represent an opinion of a patent professional and/or Sandoz entity, and is not to be understood as an evaluation of the validity or protective scope of the patents, or patentability or protective scope of the patent applications, respectively, mentioned therein.

Declaration of interest

Z Časar is employed by Lek/Sandoz. L Kovač has their PhD studies financed by Lek/Sandoz. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Authors’ contributions

The concept of the manuscript was performed by Z Časar. The design, analysis, interpretation and critical revision was performed by both authors. The manuscript was drafted by L Kovač. Both authors agree to be accountable for all aspects of the work.

Additional information

Funding

This article was funded by Lek/Sandoz.