Last month, Ironwood Pharmaceuticals (Cambridge, Massachusetts) participated in the American College of Rheumatology (ACR) Annual Meeting in Washington, DC, for the first time. This is a milestone for Ironwood, which launched Zurampic® (lesinurad) — the company’s second commercial product and its first in the rheumatology space — on October 3, 2016.
Lesinurad is indicated for hyperuricemia associated with gout in patients not reaching target serum uric acid (sUA) levels on a xanthine oxidase inhibitor (XOI) alone.1 Lesinurad is not recommended for the treatment of asymptomatic hyperuricemia and should not be used as a monotherapy.1 Ironwood licensed the US rights for lesinurad from AstraZeneca in the Spring of 2016.
Gout, the most common form of inflammatory arthritis, affecting an estimated 8 million people in the US. The disease is caused by an underlying metabolic disorder (hyperuricemia), and can lead to painful flares, characterized by excruciating pain, inflammation, swelling and tenderness in one or more joints.2-4 Patients, physicians and the media often focus on the acute phase of gout – “treating the flares” – and understandably so; my father and grandfather both had gout, and I saw firsthand how much they struggled with this disease.
Importantly, however, gout is actually a chronic disease with serious potential long-term consequences, such as repeated disability due to continuing flares, joint erosion and soft tissue damage for patients who do not maintain sUA levels to target of ≤6 mg/dL as recommended by ACR guidelines.3,5,6 Of the estimated 4 million patients with gout in the US taking an XOI, an estimated 2 million are still unable to reach target sUA levels.7-14
At this year’s meeting, Ironwood presented 16 abstracts, 4 of which highlighted the efficacy and safety data from 2 phase III extension studies of lesinurad, as well as pooled analyses from 2 extension studies and 3 phase III lesinurad clinical trials. The extension studies demonstrated continued efficacy of lesinurad plus a XOI over a 24-month period and a safety profile consistent with that observed in the phase III clinical trials, with no new safety concerns reported.15,16
In pivotal phase III trials, lesinuard, when added to allopurinol in patients with gout who failed to achieve target sUA levels with allopurinol alone, nearly doubled the number of patients who achieved sUA target <6 mg/dL at month 6, reduced the mean sUA to target <6 mg/dL by month 1, and maintained that level through month 12.1 When added to febuxostat in clinical trials, lesinurad helped a greater (but not statistically significant) proportion of patients with tophaceous gout to achieve sUA <5 mg/dL at month 6 and maintained sUA <5 mg/dL through month 12 in patients with tophaceous gout.1 The average reduction in sUA levels was similar in all clinical trials of lesinurad 200 mg plus an XOI.1
The most common adverse reactions reported in clinical trials with ZURAMPIC (in combination with an XOI and more frequently than on an XOI alone) were headache, influenza, increased blood creatinine level, and gastroesophageal reflux disease.1 It should be noted that acute renal failure has occurred with lesinurad and was more common when ZURAMPIC was given alone.1 This reinforces that ZURAMPIC should be used in combination with an XOI.
Ironwood is committed to advancing innovation in the treatment of gout. To advance knowledge and spur dialogue in the community, for example, Ironwood commissioned a survey in August 2016 of a nationally representative sample of primary care physicians and rheumatologists to better understand their perceptions of gout and its treatment. The survey findings further elucidated the significant unmet patient need: 9 in 10 of these physicians stated that treating gout to target is imperative, yet only half of them reported that their gout patients were reaching target sUA levels.17
Although there is much work to be done, the enthusiasm and growing body of scientific evidence presented at this year’s ACR annual meeting portends good news for the millions of gout patients in need.
Machelle Manuel, PhD, is vice president, Medical Scientific Affairs, at Ironwood Pharmaceuticals, the manufacturer of lesinurad.
1. ZURAMPIC® [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2015.
2. Perez-Ruiz F, Herrero-Beites A. Evaluation and treatment of gout as a chronic disease. Adv Ther. 2012;29(11):935–946.
3. Schumacher HR Jr. The pathogenesis of gout. Cleve Clin J Med. 2008;75(suppl 5):S2-S4.
4. Taylor WJ, Grainger R. Clinical features of gout. In: Terkeltaub R, ed. Gout and Other Crystal Arthropathies. 1st ed. Philadelphia: Elsevier Saunders; 2012:105-120.
5. Khanna D, FitzGerald JD, Khanna PP, Baeet S, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic non-pharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64:1431-1446.
6. Richette P, Bardin T. Gout. Lancet. 2010;375(9711):318-328.
7. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011;63(10):3136-3141.
8. Juraschek SP, Kovell LC, Miller ER 3rd, Gelber AC. Gout, urate-lowering therapy and uric acid levels among adults in the United States. Arthritis Care Res. 2015;67(4):598-592.
9. Wood R, Fermer S, Ramachandran S, et al. Patients with gout treated with conventional urate-lowering therapy: association with disease control, health-related quality of life, and work productivity. J Rheumatol. 2016;43(10);1897-1903.
10. Khanna P, Khanna D, Storgard C, et al. A world of hurt: failure to achieve treatment goals in patients with gout requires a paradigm shift. Postgrad Med. 2016;128(1):34-40.
11. Meyer M, Ford C, Harrison K, et al. Trends in medication utilization and the cost of treatment for gout. Am J Pharmacy Ben. 2015;5(3):123-128.
12. Primatesta P, Plana E, Rothenbacher D. Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population. BMC Musculoskeletal Dis. 2011;12:130. doi: 10.1186/1471-2474-12-103
13. Singh JA, Akhras KS and Shiozawa A. Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses from large U.S. managed care cohort. Arthritis Res Ther. 2015;17:120. doi: 10.1186/s13075-015-0624-3
14. AZN/Decision Resource Market Research.
15. Saag K, Becker MA, Storgard C, et al. Examination of serum uric acid (sUA) lowering and safety with extended lesinurad + allopurinol treatment in subjects with gout [abstract]. Arthritis Rheumatol. 2016;68 (suppl 10). http://acrabstracts.org/abstract/examination-of-serum-uric-acid-sua-lowering-and-safety-with-extended-lesinurad-allopurinol-treatment-in-subjects-with-gout/ Accessed October 10, 2016.
16. Bardin T, Dalbeth N, Terkeltaub R, et al. Clinical response of tophus and flares to extended use of lesinurad in combination with a xanthine oxidase inhibitor in patients with gout [abstract]. Arthritis Rheumatol. 2016;68(suppl 10). http://acrabstracts.org/abstract/clinical-response-of-tophus-and-flares-to-extended-use-of-lesinurad-in-combination-with-a-xanthine-oxidase-inhibitor-in-patients-with-gout/ Accessed October 10, 2016.
17. Nine in ten physicians agree target goal for gout is imperative, yet half of patients fail to reach it. Available at: http://news.ironwoodpharma.com/phoenix.zhtml?c=228069&p=irol-newsArticle&ID=2208364. Accessed November 29, 2016.