Phase III trial of CNTO 136 (sirukumab) meets all endpoints in severely active rheumatoid arthritis- Janssen R&D

Janssen Research & Development announced results from a pivotal Phase III study evaluating subcutaneous CNTO 136 (sirukumab) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). Data in 1,670 patients showed those receiving sirukumab demonstrated significant inhibition of radiographic progression, or joint destruction, from baseline to week 52 and improvement in signs and symptoms of RA at week 16, the study's co-primary endpoints, when compared with patients receiving placebo. The SIRROUND-D study met both co-primary endpoints evaluating treatment with sirukumab in adult patients with active RA who had an inadequate response to treatment with disease-modifying antirheumatic drugs (DMARDs).

Inhibition of radiographic progression, or joint destruction, was significantly greater among sirukumab-treated patients, with a mean change from baseline to week 52 in the van der Heijde-Sharp score of 0.50 among patients receiving sirukumab 50 mg every four weeks and 0.46 for patients receiving sirukumab 100 mg every two weeks compared with 3.69 among the placebo group. The van der Heijde-Sharp scoring method is an X-ray measure of changes in joint destruction and damage, including joint erosion and joint space narrowing. With this method, higher scores indicate greater structural damage while lower scores indicate less structural damage. Significant inhibition of radiographic progression was demonstrated in both patients naïve to biologic therapy and those treated with biologics in the past, and was seen as early as week 24. At least a 20 percent improvement in RA signs and symptoms as measured by the American College of Rheumatology (ACR20) at week 16 was achieved by 54.8 percent and 53.5 percent of patients receiving sirukumab 50 mg and sirukumab 100 mg, respectively, compared with 26.4 percent of the placebo group.

All major secondary endpoints were also met with statistical significance for both doses of sirukumab versus placebo. These were the change from baseline in the health assessment questionnaire disability index (HAQ-DI), percentage of patients achieving at least a 50 percent improvement in RA symptoms (ACR50), percentage of patients with improved disease activity score in 28 joints at week 24, and percentage of patients achieving at least a 70 percent improvement in RA signs and symptoms (for six consecutive months (major clinical response) by week 52. Sirukumab is being co-developed as part of a collaboration with GSK. This data is scheduled for presentation during the Annual European Congress of Rheumatology (EULAR 2016).