Novel Gout Treatment Boosts Response in Allopurinol Nonresponders

CHICAGO – Combined treatment with allopurinol and the novel purine nucleoside phosphorylase inhibitor BCX4208 significantly lowered serum uric acid levels in gout patients who had failed to respond to allopurinol alone, according to findings from a randomized placebo-controlled trial involving 278 adults.

Between 33% and 49% of patients who received 12 weeks of combined treatment with BCX4208 at doses ranging from 5 to 40 mg/day plus allopurinol at 300 mg/day achieved the goal serum uric acid level of less than 6.0 mg/dL, compared with only 18% of those receiving placebo and allopurinol, Dr. William P. Sheridan reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The response rates differed by BCX4208 dose, with 45%, 33%, 39%, and 49% of those receiving 5, 10, 20, and 40 mg, respectively, achieving goal serum uric acid levels. The differences between the 5, 20, and 40 mg groups and the placebo arm were statistically significant, said Dr. Sheridan of BioCryst Pharmaceuticals, Durham, N.C., which is the maker of BCX4208 and the sponsor of the study.

Gout flares occurred in 5%-11% of patient in each BCX4208 arm and in 5% of patient in the placebo group, and both the severity and frequency of adverse events were evenly distributed across dose groups. No opportunistic infections occurred.

Also, dose-related reductions in lymphocytes and lymphocyte subsets occurred during drug administration, but these appeared to plateau within 12 weeks, Dr. Sheridan said.

Discontinuations occurred in both the 20- and 40-mg groups because of confirmed CD4+ cell counts less than 350 cells/mm³. No patients in the other groups discontinued because of low CD4+ cell counts, he said.

Study participants were adults with a mean age of 49 years with a gout diagnosis and serum uric acid levels of 6.0 mg/dL or less who had not responded sufficiently after treatment with at least 2 weeks of allopurinol at 300 mg/day. All patients received colchicine or naproxen as prophylaxis for gout flares.

The participants had a high mean body mass index of 36 kg/m², and comorbidities were common; 58% had hypertension, 16% had diabetes, and 39% had hypercholesterolemia.

The findings suggest that BCX4208 is generally safe and well tolerated when combined with allopurinol, and that the combination improves the likelihood that gout patient will reach goal serum uric acid levels, Dr. Sheridan said, noting that the findings are important given that few alternatives have existed for patients who fail to reach serum uric acid goal range with a xanthine oxidase inhibitor alone.

BCX4208 appears shows promise for those patients, and an extension phase of the study is underway, he said.

"The safety and tolerability profile on BCX4208 was quite satisfactory and certainly adequate for consideration of further clinical research," he concluded, noting that phase III studies are in development.

Dr. Sheridan disclosed that he is employed by BioCryst Pharmaceuticals, which is the maker of BCX4208 and the sponsor of this study.

CHICAGO – Combined treatment with allopurinol and the novel purine nucleoside phosphorylase inhibitor BCX4208 significantly lowered serum uric acid levels in gout patients who had failed to respond to allopurinol alone, according to findings from a randomized placebo-controlled trial involving 278 adults.

Between 33% and 49% of patients who received 12 weeks of combined treatment with BCX4208 at doses ranging from 5 to 40 mg/day plus allopurinol at 300 mg/day achieved the goal serum uric acid level of less than 6.0 mg/dL, compared with only 18% of those receiving placebo and allopurinol, Dr. William P. Sheridan reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The response rates differed by BCX4208 dose, with 45%, 33%, 39%, and 49% of those receiving 5, 10, 20, and 40 mg, respectively, achieving goal serum uric acid levels. The differences between the 5, 20, and 40 mg groups and the placebo arm were statistically significant, said Dr. Sheridan of BioCryst Pharmaceuticals, Durham, N.C., which is the maker of BCX4208 and the sponsor of the study.

Gout flares occurred in 5%-11% of patient in each BCX4208 arm and in 5% of patient in the placebo group, and both the severity and frequency of adverse events were evenly distributed across dose groups. No opportunistic infections occurred.

Also, dose-related reductions in lymphocytes and lymphocyte subsets occurred during drug administration, but these appeared to plateau within 12 weeks, Dr. Sheridan said.

Discontinuations occurred in both the 20- and 40-mg groups because of confirmed CD4+ cell counts less than 350 cells/mm³. No patients in the other groups discontinued because of low CD4+ cell counts, he said.

Study participants were adults with a mean age of 49 years with a gout diagnosis and serum uric acid levels of 6.0 mg/dL or less who had not responded sufficiently after treatment with at least 2 weeks of allopurinol at 300 mg/day. All patients received colchicine or naproxen as prophylaxis for gout flares.

The participants had a high mean body mass index of 36 kg/m², and comorbidities were common; 58% had hypertension, 16% had diabetes, and 39% had hypercholesterolemia.

The findings suggest that BCX4208 is generally safe and well tolerated when combined with allopurinol, and that the combination improves the likelihood that gout patient will reach goal serum uric acid levels, Dr. Sheridan said, noting that the findings are important given that few alternatives have existed for patients who fail to reach serum uric acid goal range with a xanthine oxidase inhibitor alone.

BCX4208 appears shows promise for those patients, and an extension phase of the study is underway, he said.

"The safety and tolerability profile on BCX4208 was quite satisfactory and certainly adequate for consideration of further clinical research," he concluded, noting that phase III studies are in development.

Dr. Sheridan disclosed that he is employed by BioCryst Pharmaceuticals, which is the maker of BCX4208 and the sponsor of this study.

CHICAGO – Combined treatment with allopurinol and the novel purine nucleoside phosphorylase inhibitor BCX4208 significantly lowered serum uric acid levels in gout patients who had failed to respond to allopurinol alone, according to findings from a randomized placebo-controlled trial involving 278 adults.

Between 33% and 49% of patients who received 12 weeks of combined treatment with BCX4208 at doses ranging from 5 to 40 mg/day plus allopurinol at 300 mg/day achieved the goal serum uric acid level of less than 6.0 mg/dL, compared with only 18% of those receiving placebo and allopurinol, Dr. William P. Sheridan reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The response rates differed by BCX4208 dose, with 45%, 33%, 39%, and 49% of those receiving 5, 10, 20, and 40 mg, respectively, achieving goal serum uric acid levels. The differences between the 5, 20, and 40 mg groups and the placebo arm were statistically significant, said Dr. Sheridan of BioCryst Pharmaceuticals, Durham, N.C., which is the maker of BCX4208 and the sponsor of the study.

Gout flares occurred in 5%-11% of patient in each BCX4208 arm and in 5% of patient in the placebo group, and both the severity and frequency of adverse events were evenly distributed across dose groups. No opportunistic infections occurred.

Also, dose-related reductions in lymphocytes and lymphocyte subsets occurred during drug administration, but these appeared to plateau within 12 weeks, Dr. Sheridan said.

Discontinuations occurred in both the 20- and 40-mg groups because of confirmed CD4+ cell counts less than 350 cells/mm³. No patients in the other groups discontinued because of low CD4+ cell counts, he said.

Study participants were adults with a mean age of 49 years with a gout diagnosis and serum uric acid levels of 6.0 mg/dL or less who had not responded sufficiently after treatment with at least 2 weeks of allopurinol at 300 mg/day. All patients received colchicine or naproxen as prophylaxis for gout flares.

The participants had a high mean body mass index of 36 kg/m², and comorbidities were common; 58% had hypertension, 16% had diabetes, and 39% had hypercholesterolemia.

The findings suggest that BCX4208 is generally safe and well tolerated when combined with allopurinol, and that the combination improves the likelihood that gout patient will reach goal serum uric acid levels, Dr. Sheridan said, noting that the findings are important given that few alternatives have existed for patients who fail to reach serum uric acid goal range with a xanthine oxidase inhibitor alone.

BCX4208 appears shows promise for those patients, and an extension phase of the study is underway, he said.

"The safety and tolerability profile on BCX4208 was quite satisfactory and certainly adequate for consideration of further clinical research," he concluded, noting that phase III studies are in development.

Dr. Sheridan disclosed that he is employed by BioCryst Pharmaceuticals, which is the maker of BCX4208 and the sponsor of this study.