Here's my summary of key studies presented Tuesday.
Tofacitinib in Polyarticular JIA
Abstract L22. Dr. Hermine Brunner presented the results of a phase 3 trial of tofacitinib (Tofa) in children with polyarticular JIA. The study was atypical JIA trial design with an 18 week open-label, run-in phase wherein everyone receives Tofa 5 mg bid. Over 76% of the patients were ACR JIA30 responders and were randomized to receive either continued Tofa or placebo (PBO) therapy. The primary endpoint was the flare rated between groups up to week 44. The results were significant with flares seen in 53% of placebo and 29% of Tofa patients (p=0.003). The JIA ACR 30/50/70 responses rates remained high (71%, 67%, 54%) during the blinded part of the study. There were no unexpected adverse events in this trial. These data, along with previously done PK/PD studies, suggests that Tofa may soon be unavailable drug for children with polyarticular jia in the USA.
Anifrolumab in SLE - 2 TULIPs of Different Colors
Annifrolumab is a human monoclonal antibody to the type I IFN receptor subunit 1. Several years ago a phase 2 trial showed excellent results when Annifrolumab was given to patients with active SLE, showing significant reductions in many parameters. This led to the TULIP program - two phase 3 TULIP trials were presented at this year's ACR meeting..
TULIP 1. Was presented by Dr. Richard Furie during a plenary session and despite the enthusiasm generated by the drug in phase II, this trial failed, not meeting its primary SRI-4 endpoint. Over 450 active SLE (SLEDAI > 6) patients were randomized to receive either placebo or two doses of Anifrolumab (150mg , 300mg qd) for 52 weeks; the primary endpoint was an SRI-4 at week 52. Roughly 80% of the patients completed the trial. Response rates were equal between those treated with placebo (40.4%) or anifrolumab (36.2%). Even those SLE patients who had a high type 1 IFN signature, did not do better on this type I IFN inhibitor. Nonetheless, there were higher skin (CLASI) scores (p=0.05) and significantly better BICLA scores (37% vs. 27%) at week two; and better joint outcomes for This failed study led to a change in the study design of tulip to was
TULIP 2. This phase 3 trial enrolled 362 patience with active SLE. Included patients had to have a SLEDAI > 6, seropositivity for ANA or dsDNA and remain on background standard of care. Patients were then randomized to either receive placebo or anifrolumab 300 mg/d. The primary endpoint was the BICLA response at week 52. The interesting thing about this trial was that it originally had an SRI-4 primary endpoint but, after the failure of TULIP 1 (with an SRI-4) they petitioned for a change to the BICLA response. Over 80% of the patients enrolled in this trial had a type 1 IFN signature, 40+% wer dsDNA positive, 40% had low c3 levels and 45% took steroids > 10 mg per day. The final results of the study showed a significantly better BICLA response for the anifrolumab 300 mg (47.8%) patients compared to placebo (31.5%). Responders were also able to reduce their skin scores, as measured by CLASI. Over 50% of the patients were able to reduce their corticosteroids to < 7.5 mg per day by the end of the study. The safety signals were relatively well-balanced although there were more herpes zoster cases on anifrolumab (13 vs. 2 PBO). At this point it is unknown how the FDA will view their new drugy application for use in lupus, given that two out of the three trials were positive but only one out of the two phase 3 trials met its primary endpoint. This drug has not yet been reviewed by the FDA.