— Continued treatment with AR882 demonstrated safe, efficacious and sustained reduction in sUA at 12 months —
— AR882 achieved deep and durable tophus and crystal volume dissolution at 12 months —
SAN DIEGO, June 14, 2024 /PRNewswire/ -- Arthrosi Therapeutics, Inc., a late-stage biotechnology company developing a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and tophi in patients with gout, today announced new positive clinical data from its phase 2 AR882-203 study in patients with tophaceous gout. These data are being presented as poster presentations at the European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology, being held June 12-15 in Vienna, Austria.
"We are excited to share new data from our Phase 2 trial of AR882 highlighting its long-term durability of effect and strong safety profile, further building on the body of evidence supporting AR882 as a potentially best-in-class treatment for patients with gout," said Arthrosi's Chief Medical Officer Robert T. Keenan, MD, MPH, MBA. "There remains a significant unmet need for patients with tophaceous gout, a disease marked by chronic pain and significantly diminished functionality. This new 12-month data reinforce the promising findings from the initial 6-month treatment period of the Phase 2 trial, demonstrating safe and robust SUA lowering as well as deeper and durable tophus and crystal volume dissolution at 12 months. Based on the favorable therapeutic profile observed to date, we believe AR882 has the potential to reduce debilitating symptoms and significantly improve treatment outcomes for patients with gout. We are currently advancing AR882 in a pivotal Phase 3 program and look forward to initiating the second confirmatory phase 3 study later this year."
New Clinical Data for AR882, Arthrosi's URAT1 Inhibitor
In a poster tour presentation, Dr. Keenan will highlight new 12-month clinical data from the company's phase 2 trial in patients with chronic gouty arthritis building upon AR882's promising safety and efficacy profile and further validating its durability of response. The phase 2, randomized, open-label, global trial recruited 42 patients with at least one subcutaneous tophus. The patients were randomized equally into three treatment groups to receive a once daily dose of AR882 75 mg, AR882 50 mg + allopurinol or allopurinol up to 300 mg. At the end of 6 months, the allopurinol monotherapy group had AR882 75 mg added, while the other two groups continued the same therapy.
The data showed:
Both the AR882 75 mg and the AR882 50 + allopurinol groups demonstrated a persistent and sustained decrease in sUA throughout the 12 months.
The average baseline sUA level ranged between 9.1-9.6 mg/dL across groups. At 3 months, median patient sUA levels were reduced to 4.5, 4.7, and 6.1 mg/dL for AR882 75 mg, AR882 50 mg + allopurinol and allopurinol groups, respectively. Notably, at 12 months, sUA levels for all groups further decreased to 3.9, 4.4 mg/dL and 4.0 mg/dL for the AR882 75 mg, AR882 50 mg + allopurinol and AR882 75 mg + allopurinol groups, respectively.
During the 6-month extension phase, complete tophus resolution of at least 1 target tophus measured by digital caliper was seen in 35.7% (5/14) for the AR882 75 mg group and 36.4% (4/11) for the AR882 75 mg + allopurinol group.
From baseline to Month 6, AR882 75 mg alone or in combination with allopurinol showed reduction of total urate crystal volume of -7.5 cm3 and -10.6 cm3, respectively. AR882 75 mg as monotherapy was further evaluated through months 6 to 12 and demonstrated a sustained crystal volume reduction of -13.3 cm3. In patients with significant baseline crystal volume of ≥5.0 cm3 AR882 75 mg demonstrated a sustained -26.4 cm3 reduction at 12 months.
AR882 was well tolerated throughout 12-month chronic treatment both as a monotherapy and in combination with allopurinol.
Drug-Drug Interaction Data for AR882
In a second poster presentation, Litain Yeh, Ph.D., Chief Executive Officer of Arthrosi, will discuss in vitro and clinical data supporting AR882's potential to be safely administered to gout patients with various concomitant medications and comorbid conditions including diabetes, hypertension and hyperlipidemia.
The data show:
In vitro assessments indicated that AR882 exhibited no drug-drug interactions (DDI) with key renal, hepatic and gastrointestinal transporters as substrate or inhibitor at the relevant clinical concentration.
AR882 had no inhibitory effect on any transporters except for breast cancer resistance protein (BCRP), which plays an important role in the transport of urate, a key component in gout development.
Based on these preclinical findings, Arthrosi conducted a clinical DDI study of AR882 as an inhibitor of BCRP. Sulfasalazine, a clinical substrate of BCRP and a commonly used drug in autoimmune and rheumatic diseases, was selected for the study.
Co-administration of AR882 75 mg with sulfasalazine produced no clinically relevant alterations in the pharmacokinetics (Cmax and AUC) of sulfasalazine, suggesting no clinically significant BCRP-mediated DDI.
Details for the poster presentations are as follows:
Title: AR882, a Novel and Selective URAT1 Inhibitor, Significantly Reduced Tophi in Patients with Chronic Gouty Arthritis: Results of 12-month Outcome from a Global Trial using Digital Caliper Measurements and Dual Energy Computed Tomography
Session Title: Clinical Poster Tours: Gout treatment in 2024
Presenting Author: Robert Keenan, M.D., Chief Medical Officer of Arthrosi Therapeutics
Abstract Number: POS0268
Date/Time: Friday, June 14 / 9:30am-10:30am CEST
Title: AR882, a Selective URAT1 Inhibitor, Exhibits No Drug-Drug Interactions with Key Renal, Hepatic, and GI Transporters
Presenting Author: Litain Yeh, Ph.D, Co-Founder and Chief Executive Officer of Arthrosi Therapeutics
Abstract Number: POS0935
Date/Time: Friday, June 14 / 9:30am-10:30am CEST
Both poster presentations will be available in the "Publications" section of Arthrosi's website: .
About the AR882-203 Phase 2 Study
The Phase 2 study of AR882 in patients with tophaceous gout was a six-month, 1:1:1 randomized, global, placebo-controlled study of 42 patients with subcutaneous tophi. The mean baseline sUA among the participants ranged between 9.1-9.6 mg/dL. In the study, patients received a once daily dose of either 75 mg AR882, 50mg AR882 + allopurinol, or allopurinol up to 300mg. Serum uric acid levels (< 6, <5, <4, or <3 mg/dL) were evaluated monthly through month 6, and safety and tolerability were assessed throughout the study. Tophi measurements with calipers were completed every 4 weeks for 6 months. Patients were also imaged using Dual-Energy Computed Tomography (DECT), DECT a specialized imaging technique that is able to differentiate and identify uric acid crystals in the joints and soft tissue, allowing for quantifying uric acid crystals and tophi at baseline and 6 months. The primary efficacy endpoint was sUA change at 3 months. Secondary endpoints included complete resolution of at least one target tophus with no new tophi and no tophus showing progression. Safety assessments, including vital signs and electrocardiograms, were collected throughout the study. The trial also included a 6-month extension period designed to evaluate longer-term patient outcomes.
About Gout:
In the U.S., an estimated 13 million individuals are diagnosed with gout. Gout is a form of inflammatory arthritis that can significantly diminish mobility, functionality, and overall quality of life. Gout emerges from the crystallization of uric acid within the joints and soft tissue, instigating painful flare-ups and chronic symptoms. The kidneys play a pivotal role in the process, as they are responsible for filtering out and excreting uric acid from the body. In over 90% of gout patients, underexcretion of uric acid results in the imbalanced and elevated sUA levels that can lead to the deposition of uric acid crystals. It's essential to monitor and manage sUA levels as part of comprehensive gout treatment and prevention strategies.
About Arthrosi:
Arthrosi Therapeutics, Inc., headquartered in San Diego, CA, is focused on developing AR882, a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and Tophi in patients with gout. Gout remains a large and growing market with ~ 13M patients in the U.S. alone, ~2M of which have tophaceous gout. AR882 has demonstrated encouraging efficacy and safety compared to SOC in Phase 2 studies as well as impressive results in achieving complete resolution of tophi in a Phase 2b study. Arthrosi anticipates initiating pivotal phase 3 program in early 2024.
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