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Major Finding: After 4 weeks of treatment with a combination of 200-600 mg/day lesinurad plus allopurinol and colchicine, 71%-87% of patients had serum uric acid levels lower than 6 mg/dL, compared with 28% of patients who were treated with allopurinol, colchicine, and placebo.
Data Source: A randomized, phase II study with 208 patients who were diagnosed with gout and whose serum uric acid levels remained above 6 mg/dL despite at least 6 weeks on steady treatment with 200-600 mg/day of allo-purinol.
Disclosures: The study was funded by Ardea Biosciences, which is developing lesinurad. Dr. Perez-Ruiz said that he has had financial relationships with Ardea, Menarini, and Novartis. Dr. Dougados said he has been a consultant for and received research support from Roche.
LONDON – An investigational drug that boosts uric acid secretion led to significant cuts in serum uric acid levels during 4 weeks of treatment in a phase II study of 208 patients with allopurinol-refractory gout.
In addition, among 30 patients who remained on the uricosuric agent lesinurad for 28 weeks in an extension phase, 27 patients (90%) reached the study's target level of serum uric acid (lower than 6 mg/dL), according to Dr. Fernando Perez-Ruiz.
Treatment with dosages of 200-600 mg/day of lesinurad also appeared safe, with no adverse effects or other safety concerns seen during the limited treatment period reported, said Dr. Perez-Ruiz, a rheumatologist at Hospital de Cruces in Barakaldo, Spain.
The drug worked equally well in patients with normal renal function (a glomerular filtration rate of at least 90 mL/min per 1.73 m
Phase III Trial to Start This Year
Based on these promising early results, a phase III trial of lesinurad will start before the end of this year, said Barry D. Quart, Pharm.D., president of Ardea Biosciences, the San Diego–based company that is developing the drug.
The phase III study will likely focus on the 200-mg and 400-mg/day dosages, as over time most patients appeared to respond to these lower dosages.
“Almost no one needs 600 mg/day to get a response,” Dr. Quart said in an interview.
Although the current study used patients' serum uric acid levels of lower than 6 mg/dL as the end point and did not assess clinical features of gout, this end point is highly meaningful, said Dr. Maxime Dougados, professor of rheumatology at René Descartes University in Paris.
Gout treatment guidelines developed by the European League Against Rheumatism (EULAR) emphasize “the importance of treating patients to a target serum uric acid of less than 6 mg/dL,” commented Dr. Dougados.
New Drugs Increase Excretion
“Until now, we have drugs that decrease uric acid synthesis, but we have not recently had any drugs to increase excretion,” Dr. Dougados observed, adding that “Now we have a new drug to increase excretion, and that is very important because allopurinol is often not sufficient to achieve the target serum uric acid level.”
Lesinurad works by inhibiting URAT1, a uric acid transporter molecule in the kidney that takes uric acid out of urine and places it back into the blood.
The study led by Dr. Perez-Ruiz enrolled patients who met the 1977 gout diagnosis criteria of the American Rheumatism Association (now the American College of Rheumatology) and who had a serum uric acid level greater than 6 mg/dL despite being on a stable dose of 200-600 mg allopurinol for at least 6 weeks.
Patients were randomized to daily treatment with 200 mg, 400 mg, or 600 mg of oral lesinurad or placebo.
All patients also received a 0.5-mg or 0.6-mg daily dose of colchicine, and they all also remained on the dosage of allopurinol that they were taking at entry into the study.
After 4 weeks on treatment, the percentage of patients whose serum uric acid level had fallen below 6 mg/dL was 28% in the 72 placebo patients, and 71%, 76%, and 87% in the three lesinurad treatment groups, which each contained 42-48 patients.
The difference in the percentage of responding patients in each of the three treatment arms was statistically significant, compared with the placebo group.
“Lesinurad produced rapid and sustained reductions in uric acid levels when added on to allopurinol in patients who were not adequately responding to allopurinol alone,” Dr. Perez-Ruiz concluded.
Major Finding: After 4 weeks of treatment with a combination of 200-600 mg/day lesinurad plus allopurinol and colchicine, 71%-87% of patients had serum uric acid levels lower than 6 mg/dL, compared with 28% of patients who were treated with allopurinol, colchicine, and placebo.
Data Source: A randomized, phase II study with 208 patients who were diagnosed with gout and whose serum uric acid levels remained above 6 mg/dL despite at least 6 weeks on steady treatment with 200-600 mg/day of allo-purinol.
Disclosures: The study was funded by Ardea Biosciences, which is developing lesinurad. Dr. Perez-Ruiz said that he has had financial relationships with Ardea, Menarini, and Novartis. Dr. Dougados said he has been a consultant for and received research support from Roche.
LONDON – An investigational drug that boosts uric acid secretion led to significant cuts in serum uric acid levels during 4 weeks of treatment in a phase II study of 208 patients with allopurinol-refractory gout.
In addition, among 30 patients who remained on the uricosuric agent lesinurad for 28 weeks in an extension phase, 27 patients (90%) reached the study's target level of serum uric acid (lower than 6 mg/dL), according to Dr. Fernando Perez-Ruiz.
Treatment with dosages of 200-600 mg/day of lesinurad also appeared safe, with no adverse effects or other safety concerns seen during the limited treatment period reported, said Dr. Perez-Ruiz, a rheumatologist at Hospital de Cruces in Barakaldo, Spain.
The drug worked equally well in patients with normal renal function (a glomerular filtration rate of at least 90 mL/min per 1.73 m
Phase III Trial to Start This Year
Based on these promising early results, a phase III trial of lesinurad will start before the end of this year, said Barry D. Quart, Pharm.D., president of Ardea Biosciences, the San Diego–based company that is developing the drug.
The phase III study will likely focus on the 200-mg and 400-mg/day dosages, as over time most patients appeared to respond to these lower dosages.
“Almost no one needs 600 mg/day to get a response,” Dr. Quart said in an interview.
Although the current study used patients' serum uric acid levels of lower than 6 mg/dL as the end point and did not assess clinical features of gout, this end point is highly meaningful, said Dr. Maxime Dougados, professor of rheumatology at René Descartes University in Paris.
Gout treatment guidelines developed by the European League Against Rheumatism (EULAR) emphasize “the importance of treating patients to a target serum uric acid of less than 6 mg/dL,” commented Dr. Dougados.
New Drugs Increase Excretion
“Until now, we have drugs that decrease uric acid synthesis, but we have not recently had any drugs to increase excretion,” Dr. Dougados observed, adding that “Now we have a new drug to increase excretion, and that is very important because allopurinol is often not sufficient to achieve the target serum uric acid level.”
Lesinurad works by inhibiting URAT1, a uric acid transporter molecule in the kidney that takes uric acid out of urine and places it back into the blood.
The study led by Dr. Perez-Ruiz enrolled patients who met the 1977 gout diagnosis criteria of the American Rheumatism Association (now the American College of Rheumatology) and who had a serum uric acid level greater than 6 mg/dL despite being on a stable dose of 200-600 mg allopurinol for at least 6 weeks.
Patients were randomized to daily treatment with 200 mg, 400 mg, or 600 mg of oral lesinurad or placebo.
All patients also received a 0.5-mg or 0.6-mg daily dose of colchicine, and they all also remained on the dosage of allopurinol that they were taking at entry into the study.
After 4 weeks on treatment, the percentage of patients whose serum uric acid level had fallen below 6 mg/dL was 28% in the 72 placebo patients, and 71%, 76%, and 87% in the three lesinurad treatment groups, which each contained 42-48 patients.
The difference in the percentage of responding patients in each of the three treatment arms was statistically significant, compared with the placebo group.
“Lesinurad produced rapid and sustained reductions in uric acid levels when added on to allopurinol in patients who were not adequately responding to allopurinol alone,” Dr. Perez-Ruiz concluded.
Major Finding: After 4 weeks of treatment with a combination of 200-600 mg/day lesinurad plus allopurinol and colchicine, 71%-87% of patients had serum uric acid levels lower than 6 mg/dL, compared with 28% of patients who were treated with allopurinol, colchicine, and placebo.
Data Source: A randomized, phase II study with 208 patients who were diagnosed with gout and whose serum uric acid levels remained above 6 mg/dL despite at least 6 weeks on steady treatment with 200-600 mg/day of allo-purinol.
Disclosures: The study was funded by Ardea Biosciences, which is developing lesinurad. Dr. Perez-Ruiz said that he has had financial relationships with Ardea, Menarini, and Novartis. Dr. Dougados said he has been a consultant for and received research support from Roche.
LONDON – An investigational drug that boosts uric acid secretion led to significant cuts in serum uric acid levels during 4 weeks of treatment in a phase II study of 208 patients with allopurinol-refractory gout.
In addition, among 30 patients who remained on the uricosuric agent lesinurad for 28 weeks in an extension phase, 27 patients (90%) reached the study's target level of serum uric acid (lower than 6 mg/dL), according to Dr. Fernando Perez-Ruiz.
Treatment with dosages of 200-600 mg/day of lesinurad also appeared safe, with no adverse effects or other safety concerns seen during the limited treatment period reported, said Dr. Perez-Ruiz, a rheumatologist at Hospital de Cruces in Barakaldo, Spain.
The drug worked equally well in patients with normal renal function (a glomerular filtration rate of at least 90 mL/min per 1.73 m
Phase III Trial to Start This Year
Based on these promising early results, a phase III trial of lesinurad will start before the end of this year, said Barry D. Quart, Pharm.D., president of Ardea Biosciences, the San Diego–based company that is developing the drug.
The phase III study will likely focus on the 200-mg and 400-mg/day dosages, as over time most patients appeared to respond to these lower dosages.
“Almost no one needs 600 mg/day to get a response,” Dr. Quart said in an interview.
Although the current study used patients' serum uric acid levels of lower than 6 mg/dL as the end point and did not assess clinical features of gout, this end point is highly meaningful, said Dr. Maxime Dougados, professor of rheumatology at René Descartes University in Paris.
Gout treatment guidelines developed by the European League Against Rheumatism (EULAR) emphasize “the importance of treating patients to a target serum uric acid of less than 6 mg/dL,” commented Dr. Dougados.
New Drugs Increase Excretion
“Until now, we have drugs that decrease uric acid synthesis, but we have not recently had any drugs to increase excretion,” Dr. Dougados observed, adding that “Now we have a new drug to increase excretion, and that is very important because allopurinol is often not sufficient to achieve the target serum uric acid level.”
Lesinurad works by inhibiting URAT1, a uric acid transporter molecule in the kidney that takes uric acid out of urine and places it back into the blood.
The study led by Dr. Perez-Ruiz enrolled patients who met the 1977 gout diagnosis criteria of the American Rheumatism Association (now the American College of Rheumatology) and who had a serum uric acid level greater than 6 mg/dL despite being on a stable dose of 200-600 mg allopurinol for at least 6 weeks.
Patients were randomized to daily treatment with 200 mg, 400 mg, or 600 mg of oral lesinurad or placebo.
All patients also received a 0.5-mg or 0.6-mg daily dose of colchicine, and they all also remained on the dosage of allopurinol that they were taking at entry into the study.
After 4 weeks on treatment, the percentage of patients whose serum uric acid level had fallen below 6 mg/dL was 28% in the 72 placebo patients, and 71%, 76%, and 87% in the three lesinurad treatment groups, which each contained 42-48 patients.
The difference in the percentage of responding patients in each of the three treatment arms was statistically significant, compared with the placebo group.
“Lesinurad produced rapid and sustained reductions in uric acid levels when added on to allopurinol in patients who were not adequately responding to allopurinol alone,” Dr. Perez-Ruiz concluded.