Tuesday, 22 December 2015
AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved ZURAMPIC® (lesinurad) 200 mg tablets in combination with a xanthine oxidase inhibitor (XOI) for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone.1 ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia and should not be used as monotherapy.
ZURAMPIC inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid.1 By inhibiting URAT1, ZURAMPIC increases uric acid excretion and thereby lowers sUA.1
ZURAMPIC in combination with the current standard of care, XOIs allopurinol or febuxostat, provides a dual mechanism of action to increase excretion and decrease production of uric acid, enabling more patients with inadequately controlled gout to achieve target treatment goals.1
Sean Bohen, Executive Vice President of Global Medicines Development and Chief Medical Officer, AstraZeneca, said: “With the FDA approval of ZURAMPIC, we are pleased to offer a treatment option for the many patients with gout who are not reaching the recommended sUA treatment targets with the current standard of care.”
The FDA approval is based on data from three pivotal Phase III studies, CLEAR1, CLEAR2 and CRYSTAL. The safety and efficacy data from these pivotal Phase III combination therapy program trials represents the largest clinical trial data set of gout patients (n=1,537 total) treated with combination urate lowering therapy.2-4 In patients not reaching sUA goals, ZURAMPIC when used in combination with allopurinol resulted in approximately twice as many patients reaching American College of Rheumatology (ACR) recommended sUA targets, compared to those treated with allopurinol alone.1
ZURAMPIC has a boxed warning that provides important safety information for health care professionals, including the risk for acute kidney (renal) failure, which is more common when used without an XOI and with higher than approved doses of ZURAMPIC.
The most common adverse events (occurring in at least 2% of patients treated with ZURAMPIC 200 mg in combination with an XOI and at least 1% greater than on an XOI alone) were headache, influenza, blood creatinine increased and gastroesophageal reflux disease.1 The number and type of events were similar whether ZURAMPIC was combined with allopurinol or febuxostat.1
Gout is the most common form of inflammatory arthritis caused by hyperuricemia (elevated sUA).5,6 Gout affects millions of Americans,7 many of whom do not reach recommended sUA treatment goals on XOIs, which decrease production of uric acid.8 For those inadequately controlled patients, the addition of a urate-lowering therapy to increase excretion of uric acid, may help them achieve treatment goals.9
Dr. Lawrence Edwards, Chairman and Chief Executive Officer of the Gout and Uric Acid Education Society (GUAES) said: “Another option to treat gout is long overdue given there has been limited therapy innovation over the last 50 years. Combination therapy with ZURAMPIC is an important addition to the medicines available to physicians that will help more gout patients reach their serum uric acid treatment targets.”
Important Safety Information
WARNING: RISK OF ACUTE RENAL FAILURE MORE COMMON WHEN USED WITHOUT A XANTHINE OXIDASE INHIBITOR (XOI)
- Acute renal failure has occurred with ZURAMPIC and was more common when ZURAMPIC was given alone
- ZURAMPIC should be used in combination with an XOI
- Severe renal impairment (eCLcr less than 30 mL/min), end-stage renal disease, kidney transplant recipients, or patients on dialysis
- Tumor lysis syndrome or Lesch-Nyhan syndrome
Warnings and Precautions:
- Renal events: Adverse reactions related to renal function have occurred after initiating ZURAMPIC. A higher incidence was observed at the 400-mg dose, with the highest incidence occurring with monotherapy use. Monitor renal function at initiation and during therapy with ZURAMPIC, particularly in patients with eCLcr below 60 mL/min, and evaluate for signs and symptoms of acute uric acid nephropathy. ZURAMPIC should not be initiated in patients with an eCLcr less than 45 mL/min.
- Cardiovascular events: Major adverse cardiovascular events were observed with ZURAMPIC; a causal relationship has not been established
- Most common adverse reactions with ZURAMPIC (in combination with an XOI and more frequently than on an XOI alone) were headache, influenza, blood creatinine increased, and gastroesophageal reflux disease
Indication and Limitations of Use for ZURAMPIC:
ZURAMPIC is a URAT1 inhibitor indicated in combination with an XOI for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with an XOI alone.
- ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia
- ZURAMPIC should not be used as monotherapy
NOTES TO EDITORS
About ZURAMPIC® (lesinurad) 200 mg tablets
ZURAMPIC® (lesinurad) 200 mg tablets inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid.1 By inhibiting URAT1, ZURAMPIC increases uric acid excretion and thereby lowers serum uric acid (sUA).1 ZURAMPIC also inhibits organic anion transporter (OAT) 4 a uric acid transporter involved in diuretic-induced hyperuricemia.
About Hyperuricemia and Gout
Gout is the most common form of inflammatory arthritis.5,6 Currently, there are more than 8.3 million patients with gout in the US.7 The underlying cause of gout is hyperuricemia (elevated serum uric acid (sUA)).6 The goal of sUA lowering treatment is to reduce sUA levels to the target level of <6.0 mg/dL as recommended by the American College of Rheumatology (ACR).9In those with greater disease severity and urate burden, such as those with tophi, ACR guidelines recommend lowering sUA to <5.0 mg/dL to achieve better disease control.9
Among patients treated in clinical trials, less than 50% of patients on allopurinol 300 mg reached sUA target levels <6.0 mg/dL.10-12 This suggests approximately two million gout patients in the US on urate lowering therapy remain inadequately controlled.7,10-13 For patients who cannot reach target on a xanthine oxidase inhibitor (XOI) alone, the current ACR guidelines recommend adding an agent that increases uric acid excretion.9
About Ardea Biosciences
Ardea Biosciences is a member of the AstraZeneca Group, located in San Diego, California. Ardea is leading the development of AstraZeneca’s gout portfolio, including ZURAMPIC and RDEA3170. RDEA3170 is a potent selective uric acid reabsorption inhibitor (SURI), also intended for use as a combination urate lowering therapy with xanthine oxidase inhibitors (XOIs). RDEA3170 is our lead investigational urate lowering therapy (ULT) in Asia and is currently entering a Phase IIb trial worldwide.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca-us.com.
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- Prescribing Information for ZURAMPIC. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- Saag K, et al. Lesinurad, A Selective Uric Acid Reabsorption Inhibitor, In Combination With Allopurinol: Results From A Phase III Study In Gout Patients Having An Inadequate Response To Standard Of Care (CLEAR 1). Presented at the 16th EULAR Annual European Congress of Rheumatology, Rome, Italy, June 10-13, 2015.
- Bardin T, et al. Lesinurad, A Selective Uric Acid Reabsorption Inhibitor, In Combination With Allopurinol: Results From A Phase III Study In Gout Patients Having An Inadequate Response To Standard Of Care (CLEAR 2). Presented at the 16th EULAR Annual European Congress of Rheumatology, Rome, Italy, June 10-13, 2015.
- Dalbeth N, et al. Lesinurad, a Novel Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat, in Patients With Tophaceous Gout: The CRYSTAL Phase III Clinical Trial. Presented at the 16th EULAR Annual European Congress of Rheumatology, Rome, Italy, June 10-13, 2015.
- Perez-Ruiz F, Herrero-Beites A. Evaluation and Treatment of Gout as a Chronic Disease. Adv Ther. 2012;29(11):935–946.
- Schumacher HR. The pathogenesis of gout. Cleve Clin J Med. 2008;75(5):S2-S4.
- Zhu Y, et al. Prevalence of Gout and Hyperuricemia in the US General Population.Arthritis Rheum. 2011;63:3136–3141.
- Singh J, Akhras K, 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.
- Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64:1431-1446.
- Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461.
- Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial.Arthritis Res Ther. 2010;12(2):R63.
- Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59(11):1540-1548.
- Data on file, 3189402, AstraZeneca Pharmaceuticals LP.
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