arhalofenate (MBX-102) / J&J, Gilead - LARVOL DELTA

Pipeline Therapies for Gout. (PubMed, Curr Rheumatol Rep) - "Dotinurad may function in the setting of decreased renal function. Arhalofenate has anti-URAT-1 activity and may also blunt gout flares. A new xanthine oxidase inhibitor (XOI), tigulixostat, is under study...Dapansutrile, an oral agent under investigation, inhibits activation of the NLRP3 inflammasome and may be an effective anti-inflammatory. New treatments for gout that are under study may work in the setting of comorbidities, simplify management, utilize new mechanisms, or have reduced side effects."

Journal • Review • Gout • Inflammatory Arthritis • Nephrology • Renal Calculi • Renal Disease • Rheumatology • IL1B • NLRP3

What's new on the front-line of gout pharmacotherapy? (PubMed, Expert Opin Pharmacother) - "Regarding gout flare pharmacotherapy NSAIDs, colchicine and glucocorticoids are first line agents...Allopurinol is an agent of first choice for urate lowering therapy (ULT)...Febuxostat is another efficacious urate lowering therapy but it has received U.S. FDA black box warning for cardiovascular safety and careful consideration is warranted before its initiation in patients with high cardiovascular risk. Novel uricosurics are a class for continued drug development; verinurad and arhalofenate are agents with future promise...Its immunogenicity significantly threatens the achievement of sustained urate lowering responses. Abrogating pegloticase's immunogenicity with immunomodulatory co-therapy may lend to sustained efficacy."

Journal • Cardiovascular • Gout • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology • IL1B

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs. (PubMed, Nutr Metab Cardiovasc Dis) - "Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes."

Clinical • Journal • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications. (PubMed) - Ther Adv Musculoskelet Dis - "Drugs in phases I and II of development will be discussed, along with new agents and therapeutic classes, such as purine nucleoside phosphorylase inhibitors and dual-action drugs. These new developments are encouraging, and will hopefully contribute to a more adequate management of hyperuricemia in gout."

Journal • Review • Biosimilar • Immunology

The mechanism of Arhalofenate in alleviating hyperuricemia-Activating PPARγ thereby reducing caspase-1 activity. (PubMed, Drug Dev Res) - "Then cells were treated with Arha, caspase-1 inhibitor Belnacasan (Beln), caspase-11 inhibitor Wedelolactone (Wede) and PPARγ inhibitor Mifobate, respectively. Besides, the co-treatment of Mifobate blunted the effects of Arha on cell viability and expression of GSDMD, TLR4, and caspase-1. In conclusion, Arha inhibited UA transport as well as preventing inflammation and pyroptosis via activating PPARγ thereby blocking caspase-1 activation of HUA in vitro."

Journal • Gout • Immunology • Nephrology • Renal Disease • Rheumatology • IL18 • TLR4

Evaluate the PK, PD, and Safety of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Patients With Gout (clinicaltrials.gov) - P2; N=32; Recruiting; Sponsor: CymaBay Therapeutics, Inc.

New P2 trial • Biosimilar • Immunology

Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. (PubMed, Arthritis Res Ther) - "Arhalofenate acid is anti-inflammatory and acts via AMPK activation and its downstream signaling in macrophages. These effects likely contribute to a reduction of gout flares."

Journal

Safety and tolerability of available urate-lowering drugs: a critical review. (PubMed, Expert Opin Drug Saf) - "...Expert opinion: Older drugs for ULT like allopurinol are well studied and extensively described from typical adverse effects (mild skin rash) to unusual fatal reactions, while febuxostat seems to be overall well tolerated. More evidence is required to define the safety profile of topiroxostat, arhalofenate, tranilast, and sulfinpyrazone. Furthermore, there are some unanswered questions about the pharmacological interactions of probenecid and the hepatotoxicity of benzbromarone. Despite a limited use in clinical practice, combination therapy with lesinurad or verinurad and XOI is not frequently accompanied by side effects. Rasburicase and pegloticase are usually well tolerated with some specific exceptions. Before prescribing UL drugs, physicians should take into account their safety profile tailoring the treatment on the patient characteristics."

Clinical • Journal

Uricosuric drugs: old and new (BSR 2019) - "...Probenecid, sulphinpyrazone, and benzbromarone were used either in monotherapy or combination with allopurinol based on empiric experience, a black legend for uricosurics emerging as scarcely useful, high risk medications. The development of new medications, such as lesinirad, verinurad, arhalofenate, has provided new insights to the clinical use, safety and effectivess issues of uricosuric medications...The advent of lesinurad has raised once again a concern for renal safety concerning uricosurics. Once again no positioning has been made by EMA, FDA, or label on how to manage lesiniurad in clinical practice. This session will intend to review mechanisms of action, clinical evaluation of safety risk factors prior to prescription and during follow-up, along with practical hintsto manage uricosurics both in monotherapy and combination in clinical practice."