Regulatory Decision Summary for Simponi I.V.

For this submission, clinical data from a Phase 3, uncontrolled, open-label study (Study CNTO148JIA3003) were provided. Study CNTO148JIA3003 was a 52-week pharmacokinetic (PK), safety and efficacy study conducted in 127 pJIA patients with active disease, ages 2 to < 18 years, with an inadequate response to or inability to tolerate methotrexate (MTX), who received Simponi I.V. 80 mg/m² at Weeks 0 and 4, and every 8 weeks (q8w) thereafter. Subjects who completed the Week 52 visit had the option to continue treatment with Simponi I.V. through Week 244.

The efficacy of IV golimumab in pJIA is based on exposure and extrapolation of established efficacy of Simponi I.V. in adults with rheumatoid arthritis (RA). The similarities between the clinical presentation, disease progression and responsiveness to therapies, including tumour necrosis factor (TNF)-alpha inhibitors, of pJIA and RA support the extrapolation of efficacy based on exposure-matching. In addition, supportive numerical trends of improvement from baseline were observed for the exploratory efficacy endpoints in Study CNTO148JIA3003 in active pJIA.

Exploratory efficacy endpoints were evaluated every 4 weeks during the 52-week study period of Study CNTO148JIA3003. Based on JIA American College of Rheumatology (ACR) response, treatment with Simponi I.V. resulted in reductions in the signs and symptoms of pJIA. These improvements were noted by Week 4, increased through Week 28, and maintained through 52 weeks of treatment. The proportions of subjects who achieved a JIA ACR 30 or 90 response were 83.5% and 46.5%, respectively, at Week 28 and 75.6% and 48.8%, respectively, at Week 52. Approximately one-third of subjects met inactive disease criteria by Week 28 as well as at Week 52. At Week 28, 1.6% of subjects receiving treatment for pJIA achieved clinical remission, which increased to 12.6% at Week 52. Overall, treatment with Simponi I.V. resulted in clinically meaningful reductions in the signs and symptoms of pJIA and this effect was maintained through Week 52.

The proportion of subjects treated with golimumab who experienced at least 1 adverse event (AE) through week 28 was 77.2% and through week 52 was 85.0%. The system organ class (SOC) with the highest proportion of subjects with AEs was infections and infestations through week 28 (57.5%) and through week 52 (66.9%). There were no reported deaths through week 52; however, 1 death due to septic shock was reported after week 52 and considered related to the drug. Discontinuations from treatment due to AEs occurred in 11 subjects. There were 83 subjects (65.4%) reporting infection as an AE through week 52. The most frequently reported infections were upper respiratory tract infections, nasopharyngitis, gastroenteritis, and tonsillitis. Infusion reactions were reported in 3 subjects and not considered to be serious or severe type resulting in discontinuation of study drug.

One newly diagnosed malignancy (mycosis fungoides) was reported through week 52. This malignancy was considered to be serious, possibly related to golimumab and resulted in discontinuation of treatment. One subject developed a new autoimmune disorder of SLE leading to discontinuation of treatment. There were no anaphylactic or serum sickness reactions, demyelinating events or clinically relevant hepatobiliary events through week 52. The overall safety profile of golimumab in pediatric subjects was comparable to adults and no new safety signals were identified.

Overall, the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) considers there to be sufficient evidence to support a positive benefit/risk profile for Simponi I.V. in the treatment of active pJIA in children 2 years of age and older.