When added to allopurinol in patients with gout who failed to achieve target sUA levels with allopurinol,

ZURAMPIC nearly doubled the number of patients who achieved sUA target <6 mg/dL at Month 61,2

Significant target sUA achievement (<6 mg/dL) at Month 6 with ZURAMPIC in combination vs allopurinol alone

Target sUA Achievement (<6 mg/dL) at < Month 6 with ZURAMPIC in combination vs allopurinol alone

CLEAR 1: Difference of proportion 0.26 (95% C.I. 0.17, 0.36) CLEAR 2: Difference of proportion 0.32 (95% C.I. 0.23, 0.41)

Clinical Trial Design1,2

CLEAR 1 (N=402: 201 in the ZURAMPIC 200 mg in combination with allopurinol group and 201 in the allopurinol-alone group) and CLEAR 2 (N=410: 204 in the ZURAMPIC 200 mg in combination with allopurinol group and 206 in the allopurinol-alone group) are phase III, randomized, double-blind, multicenter, placebo-controlled, clinical studies to evaluate the efficacy and safety of ZURAMPIC and allopurinol compared with allopurinol alone in adult subjects with hyperuricemia and gout. The primary endpoint for both studies was to determine the proportion of subjects with an sUA level that is <6.0 mg/dL by Month 6.

Two phase III, randomized, double-blind, multicenter, placebo-controlled clinical trials of ZURAMPIC in combination with allopurinol in adult patients with gout

ZURAMPIC Efficacy Study Design

Key inclusion criteria

  • Stable dose of allopurinol, 300 mg to 900 mg (200 mg for renal impairment) for at least 8 weeks prior to screening
  • sUA ≥6.5 mg/dL at screening and ≥6 mg/dL at Day 7 visit
  • Reported at least 2 gout flares in the prior 12 months

Key exclusion criteria

  • Experiencing an acute gout flare that has not resolved at least 7 days before baseline visit
  • Taking any other ULT approved for the treatment of gout besides allopurinol
  • Known hypersensitivity or allergy to allopurinol
  • Estimated creatinine clearance <30 mL/min

At baseline

  • 62% of patients across ZURAMPIC clinical trials had mild or moderate renal impairment
  • 12% of patients in the clinical trials had a history of kidney stones
  • 79% of patients had at least 1 comorbid condition, including hypertension (65%), hyperlipidemia (45%), and diabetes (17%)

When added to allopurinol in patients with gout who failed to achieve target sUA levels with allopurinol,

Mean sUA levels with ZURAMPIC in combination vs allopurinol alone over study duration

Target sUA Achievement (<6 mg/dL) at < Month 6 with ZURAMPIC in combination vs allopurinol alone

Data in the chart are pooled results from CLEAR 1 and CLEAR 2.

Clinical Trial Design1,2

CLEAR 1 (N=402: 201 in the ZURAMPIC 200 mg in combination with allopurinol group and 201 in the allopurinol-alone group) and CLEAR 2 (N=410: 204 in the ZURAMPIC 200 mg in combination with allopurinol group and 206 in the allopurinol-alone group) are phase III, randomized, double-blind, multicenter, placebo-controlled, clinical studies to evaluate the efficacy and safety of ZURAMPIC and allopurinol compared with allopurinol alone in adult subjects with hyperuricemia and gout. The primary endpoint for both studies was to determine the proportion of subjects with an sUA level that is <6.0 mg/dL by Month 6.

Two phase III, randomized, double-blind, multicenter, placebo-controlled clinical trials of ZURAMPIC in combination with allopurinol in adult patients with gout

ZURAMPIC Efficacy Study Design

Key inclusion criteria

  • Stable dose of allopurinol, 300 mg to 900 mg (200 mg for renal impairment) for at least 8 weeks prior to screening
  • sUA ≥6.5 mg/dL at screening and ≥6 mg/dL at Day 7 visit
  • Reported at least 2 gout flares in the prior 12 months

Key exclusion criteria

  • Experiencing an acute gout flare that has not resolved at least 7 days before baseline visit
  • Taking any other ULT approved for the treatment of gout besides allopurinol
  • Known hypersensitivity or allergy to allopurinol
  • Estimated creatinine clearance <30 mL/min

At baseline

  • 62% of patients across ZURAMPIC clinical trials had mild or moderate renal impairment
  • 12% of patients in the clinical trials had a history of kidney stones
  • 79% of patients had at least 1 comorbid condition, including hypertension (65%), hyperlipidemia (45%), and diabetes (17%)

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Limitations of Use for ZURAMPIC:

  • ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia
  • ZURAMPIC should not be used as monotherapy

IMPORTANT SAFETY INFORMATION ABOUT ZURAMPIC

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

Contraindications:

  • 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 or with serum creatinine elevations 1.5 to 2 times the pre-treatment value, and evaluate for signs and symptoms of acute uric acid nephropathy. Interrupt treatment with ZURAMPIC if serum creatinine is elevated to greater than 2 times the pre-treatment value or if there are symptoms that may indicate acute uric acid nephropathy. ZURAMPIC should not be restarted without another explanation for the serum creatinine abnormalities. ZURAMPIC should not be initiated in patients with an eCLcr less than 45 mL/min
  • Cardiovascular events: In clinical trials, major adverse cardiovascular events (defined as cardiovascular deaths, non-fatal myocardial infarctions, or non-fatal strokes) were observed with ZURAMPIC. A causal relationship has not been established.

Adverse Reactions:

  • 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

Please see full Prescribing Information, including Boxed WARNING and Medication Guide.

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Limitations of Use for ZURAMPIC:

  • ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia
  • ZURAMPIC should not be used as monotherapy

IMPORTANT SAFETY INFORMATION ABOUT ZURAMPIC

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

Contraindications:

  • 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 or with serum creatinine elevations 1.5 to 2 times the pre-treatment value, and evaluate for signs and symptoms of acute uric acid nephropathy. Interrupt treatment with ZURAMPIC if serum creatinine is elevated to greater than 2 times the pre-treatment value or if there are symptoms that may indicate acute uric acid nephropathy. ZURAMPIC should not be restarted without another explanation for the serum creatinine abnormalities. ZURAMPIC should not be initiated in patients with an eCLcr less than 45 mL/min
  • Cardiovascular events: In clinical trials, major adverse cardiovascular events (defined as cardiovascular deaths, non-fatal myocardial infarctions, or non-fatal strokes) were observed with ZURAMPIC. A causal relationship has not been established.

Adverse Reactions:

  • 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

Please see full Prescribing Information, including Boxed WARNING and Medication Guide.

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