Gout is an inflammatory arthritic disease resulting from urate crystal accumulation in and around joint tissues. It is frequently associated with comorbidities such as metabolic syndrome, cardiovascular disease, and chronic kidney disease. Urate lowering therapy is effective for managing chronic gout by maintaining serum urate (sUA) levels below 5 to 6 mg/dL. Allopurinol is first line therapy of gout in ACR guidelines. However, on average, 10-30% of patients do not respond and are intolerant to allopurinol. The second line therapy, febuxostat recently received a black box warning from FDA for cardiovascular risk. Due to poor tolerability, pegloticase is a third-line treatment and is reserved for patients with severe gout or those refractory to conventional therapy. Currently there is no gout medication which consistently lowers serum urate levels below 5 mg/dL to achieve clinical benefits such as flare and/or tophi reduction.
AR882 is a potent uricosuric drug undergoing development for the treatment of gout. In a phase 2a study (Study 201) in gout patients, AR882 50 mg reduced sUA levels to <5 mg/dL in 93% of patients, versus 11% and 33% for allopurinol 300 mg and febuxostat 40 mg, respectively. AR882 75 mg reduced sUA levels to <4 mg/dL in 88% of patients, versus none for allopurinol 300 mg and febuxostat 40 mg, respectively (Figure 1). The strong potency provides high potential to reduce flares and resolve tophi.
ALLO: allopurinol; FBX: febuxostat
Figure 1. Response Rates for Categorical Reductions in sUA following Treatment with AR882 versus Allopurinol and Febuxostat
| Clinical Study | Description | Status | Study Outcome |
|---|---|---|---|
| AR882-101 | Phase 1 Single Ascending Doses of AR882 in Healthy Male Adults NCT04347005 | Completed | Published in 2019 Conference of American College of Rheumatology, Atlanta
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| AR882-102 | Phase 1 Multiple Ascending Dose Study of AR882 in Healthy Male Adults NCT04314986 | Completed | Published in 2020 American College of Rheumatology Convergence
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| AR882-103 | Phase 1 AME Study of [14C]AR882 in Healthy Male Adults NCT04508426 | Completed | Published in 2021 American College of Rheumatology Convergence |
| AR882-104 | Phase 1 Pharmacokinetic and Pharmacodynamic Study of AR882 in Subjects with Various Degrees of Renal Impairment NCT04646889 | Ongoing | Published in 2021 American College of Rheumatology Convergence |
| AR882-201 | Phase 2a Study of AR882 Alone or in Combination with Febuxostat or Allopurinol in Gout Patients NCT04155918 | Completed | Published in 2020 American College of Rheumatology Convergence and 2021 European League against Rheumatism (EULAR) Convergence
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| AR882-202 | Phase 2b Randomized Study to Evaluate the Safety and Efficacy of AR882 versus Placebo in Gout Patients | Completed | Future publication |
| AR882-203 | Phase 2 Randomized Study to Evaluate the Safety and Efficacy of AR882 versus Allopurinol in Patients with Tophaceous Gout | On-going | Future publication |
Expanded Access Policy
Arthrosi Therapeutics understands that some patients may wish to access investigational medicines that are not yet approved by the FDA and other regulatory authorities. The most appropriate way for patients to access our investigational products is by participating in our clinical trials, which are managed by a team of medical experts and are designed to determine whether the investigational products are safe and effective. These clinical studies provide insight to the mechanism of action, safety, and efficacy of these products so that the benefits and risks can be adequately understood, and to ensure that quality of life improvements can be considered against any potential adverse effects. The new drug approval process ensures treatments have undergone rigorous evaluation to ensure the benefits outweigh the risks of treatment for the proposed use. Patients who are interested in participating in one of our studies are encouraged to discuss their specific needs with their physician. Information regarding our ongoing clinical trials can be accessed at www.clinicaltrials.gov.
Arthrosi Therapeutics understands there may be patients interested in obtaining access to our investigational products for treatment under an Expanded Access program. However, at this stage of the development of our products Arthrosi Therapeutics does not provide access to our investigational products through expanded access. In the event that Arthrosi Therapeutics decides to make its investigational product candidates available on an expanded access basis, this policy will be updated with a hyperlink to the expanded access record on clinicaltrials.gov after such record becomes active.
In accordance with the 21st Century Cures Act, this policy may be revised at any time. Should you have additional questions, please reach out to your physician, or contact info@arthrosi.com.