Investigational drugs for hyperuricemia, an update on recent developments

ABSTRACT

Introduction: The significant proportion of gout patients not reaching serum urate levels below 6.0 mg/dL and the debated pathogenicity of hyperuricemia (HU) itself motivate investigators to develop new drugs to decrease uricemia.

Areas covered: This review discusses the drugs considered to be in active development from pre-clinical to phase III studies. This review covers 11 drugs in development, including a xanthine oxidase inhibitor (topiroxostat), uricosurics (verinurad, arhalofenate, UR-1102, tranilast), dual inhibitors (RLBN1001, KUX-1151), a uricase (pergsiticase), an inhibitor of hypoxanthine production (ulodesine), and drugs with yet-to-explain mechanisms of action (levotofisopam, tuna extracts).

Expert opinion: Drugs well advanced in their development – particularly arhalofenate, verinurad and topiroxostat – open the prospect of patient-comorbidity-tailored HU management. Development of novel therapies provides new insight into our understanding of gout and HU, particularly potential pathogenicity. Apart from potency to decrease serum urate levels and good tolerance profiles, novel therapies will need to focus on administration modalities facilitating treatment adherence.

KEYWORDS:

• Gout
• Hyperuricemia
• arhalofenate
• verinurad
• topiroxostat

Article highlights

• Most known targets of urate formation and elimination are being targeted by novel drugs in development, apart from ABCG2

• Arhalofenate, verinurad and topiroxostat are the drugs for HU the most advanced in their development

• Verinurad is a very promising specific inhibitor of URAT1 with high affinity

• Topiroxostat and verinurad are being evaluated for the treatment of HU with other outcomes than gout

• Pegsiticase provides a potent uricase activity and is aiming to decrease the inherent immunogenicity of recombinant uricases

This box summarizes key points contained in the article.

Declaration of Interest

T. Pascart received fees from Ipsen and research funding from Horizon Pharma. P. Richette received fees from Ipsen, Menarini, Savient, Grunenthal and AstraZeneca. 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.

Additional information

Funding

This paper was not funded.