what is gout?
- Gout is the most common form of inflammatory arthritis. It is a condition that is often very debilitating for patients characterized by sudden, severe attacks of pain, swelling, redness and tenderness in one or more joints.
- This disease arises from excess uric acid in the body, known as ‘hyperuricemia,’ typically defined as serum uric acid (sUA) levels > 6.8 mg/dL, which causes the buildup of uric acid crystals and inflammation in the joints.
- Tophaceous gout occurs in people with undertreated chronic disease, where uric acid crystals form masses of white growths (tophi) around the joints and other tissues.
what are the treatment options?
First-line treatment options:
- Usually involves medicines called xanthine oxidase inhibitors (XOI), such as allopurinol, which aim to reduce uric acid levels by lowering the body’s production of uric acid.
- Febuxostat is another alternative XOI that is more potent than allopurinol but is used less in the US due to a CV boxed warning.
Last-line treatment option:
- For patients with severe, chronic, refractory gout who do not respond to first-line therapies, treatment options are very limited. The most severe patients may be treated with an intravenously administered Uricase (Krystexxa®) as a last-line option; however, this requires supervised administration due to the potential side effects.
While several urate-lowering therapies are effective, a large proportion of patients treated do not achieve the recommended sUA target levels and require additional treatment to control their disease. The gout treatment paradigm has a large unmet need between first-line XOIs and last-line Uricase.
about dotinurad
Crystalys Therapeutics is developing dotinurad as a second-line therapy to address the significant unmet medical needs of people living with gout.
Dotinurad is a novel, once-daily, oral, highly selective urate transporter 1 (URAT1) inhibitor designed to increase uric acid excretion by the kidney. URAT1 is a major urate transporter involved in renal uric acid reabsorption and excretion. Dotinurad has prior clinical validation in patients with hyperuricemia with or without gout and has been studied extensively in Japan, China and other Asian markets.
Next-generation therapy for Gout
Dotinurad has the potential to be an effective second-line oral therapy for patients who have failed to respond adequately to first-line urate-lowering therapies such as allopurinol. By lowering serum uric acid through selective URAT1 inhibition, dotinurad may help reduce gout flares and resolve tophi while addressing a significant treatment gap between xanthine oxidase inhibitors and intravenous uricase.
Proven in clinical studies
Dotinurad has been investigated in 22 completed clinical studies involving more than 1,300 participants, demonstrating a well-characterized safety profile and robust urate-lowering efficacy in participants with hyperuricemia with or without gout. Crystalys believes these reductions in serum uric acid will be associated with clinically meaningful outcomes.
In addition, clinical studies conducted in Japan and China have demonstrated that dotinurad achieves consistent and significant reductions in serum uric acid, with a well-characterized safety profile, supporting its regulatory approval and clinical use since its initial launch in Japan in 2020 and subsequent expansion across Asian markets.
Approved for clinical use
Dotinurad is currently approved in Japan, China, the Philippines, Taiwan and Thailand as a once-daily oral therapy for hyperuricemia with or without gout.
Actively treating patients
More than 2.2 million patients have been treated with dotinurad since its launch in Japan in 2020.
Dotinurad has the potential to be an effective solution as a second-line therapy to reduce gout flare and tophi, targeting patients who have failed to respond to first-line therapies such as allopurinol.
Dotinurad is not approved for any indication in North America or Europe and remains an investigational product in those regions.
clinical studies in progress
Crystalys is currently conducting multiple Phase 2 and 3 clinical trials in the U.S. and E.U. to evaluate dotinurad’s safety & efficacy in people with gout. Data from these clinical trials and the extensive safety and efficacy experience from Asia will form the basis of our NDA and MAA regulatory submissions for the approval to treat hyperuricemia associated with gout.
The AMETHYST study (NCT07535034) is a U.S. Phase 2, randomized, double-blind, placebo-controlled multicenter study that will evaluate the safety and efficacy of dotinurad in ~90 adult participants who are intolerant to xanthine oxidase inhibitors (XOI) or failed uricase treatment.
Objectives
- To evaluate the efficacy of dotinurad in lowering sUA at week 24 in adult participants with gout who are XOI intolerant or have failed uricase.
- To assess the safety and tolerability of dotinurad in adult participants with gout who are XOI intolerant or have failed uricase.
The Amethyst Study
The RUBY Study
The RUBY study (NCT07089875) is a U.S. and European Phase 3, randomized, double-blind, multicenter study that will evaluate the safety and efficacy of dotinurad compared with a physician-determined stable dose of allopurinol in ~500 adult participants with hyperuricemia associated with gout.
Objectives
- To evaluate the efficacy of dotinurad in lowering sUA at week 24 compared to allopurinol in adult participants with hyperuricemia associated with gout.
- To evaluate the efficacy of dotinurad in reducing gout flares and other clinically relevant efficacy measures compared to allopurinol.
- To assess the safety and tolerability of dotinurad compared to allopurinol.
The TOPAZ study (NCT07089888) is a U.S. Phase 3, randomized, double-blind, multicenter study that will evaluate the safety and efficacy of dotinurad compared to allopurinol in ~250 adult participants with tophaceous gout.
Objectives
- To evaluate the efficacy of dotinurad in lowering sUA at week 24 compared to allopurinol in adult participants with tophaceous gout.
- To evaluate the efficacy of dotinurad at resolving tophi, reducing gout flares, and reducing sUA compared to allopurinol.
- To assess the safety and tolerability of dotinurad compared to allopurinol.
The TOPAZ Study
