Phase III Results for Tasocitinib Generate Buzz

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.

NEW YORK — Encouraging results from a phase III study of the oral Janus kinase 3 inhibitor tasocitinib used as monotherapy for rheumatoid arthritis have rheumatologists anticipating the possibility of a new oral disease-modifying antirheumatic drug, according to Dr. Yusuf Yazici

Tasocitinib (CP-690550) is a small-molecule, oral JAK inhibitor that blocks cytokine signaling, cytokine-induced gene expression, and activation of cells involved in the immune and inflammatory responses.

Findings from the studies “look promising,” remarked Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment, and Research Center at New York University Hospital for Joint Diseases.

In this 6-month randomized, double-blind, placebo-controlled study, 243 RA patients who had failed at least one prior disease-modifying antirheumatic drug (DMARD) trial were treated for 3 months with 5 mg of tasocitinib b.i.d., 245 patients were given 10 mg of tasocitinib b.i.d., and 122 were given placebo. After 3 months, half of the placebo-treated patients were switched to 5 mg of tasocitinib and half were switched to 10 mg of tasocitinib.

At 3 months, the American College of Rheumatology (ACR) 20 response rates for 5 mg and 10 mg of tasocitinib were 60% and 66%, respectively, which were significantly higher than the 27% rate seen with placebo (P less than .0001). Just over 20% of patients on the 10-mg dose and 15% of those on the 5-mg pill achieved ACR 70, compared with 5% of those receiving placebo.

Significant differences for each tasocitinib dose compared with placebo were also found for another primary end point, the least squares mean change in the Health Assessment Questionnaire Disability Index (−0.31 and −0.38, respectively; P less than .0001).

The percentage of patients in disease remission (defined as a disease activity score [DAS] less than 2.6) was the third primary efficacy end point. No significant differences between treatment and placebo were found (6% for the 5-mg tasocitinib group vs. 4% for placebo, P = .505), although there was a trend toward significance for the 10-mg group (10%, P = .056). Significant differences were found on DAS improvement between each of the tasocitinib doses and placebo at 3 months (P less than .0001).

Meaningful differences were found as early as the second week on the ACR 20 for both tasocitinib doses, on the ACR 50 with the 10-mg dose, and on the ACR 70 for both doses.

In the first 3 months, 330 patients had 701 treatment-emergent adverse events (AEs), with a similar frequency in each of the tasocitinib and placebo groups. Thirteen patients discontinued treatment because of treatment-emergent AEs – there were no between-group differences. No deaths were reported. A total of 25 patients developed serious AEs (6 in the 5-mg tasocitinib group, 12 in the 10-mg tasocitinib group, 5 in the group that switched from placebo to 5-mg tasocitinib, and 2 in the group that switched from placebo to 10-mg tasocitinib).

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene Corporation, Genentech, Roche, and UCB.