Date: 2012-06-06
Type of information: Results
phase: 3
Announcement: results
Company: Novartis (Switzerland)
Product: ACZ885 (canakinumab)
Action
mechanism: ACZ885 is a fully human monoclonal antibody that inhibits IL-1 beta, which is an important part of the body's immune system defenses. Excessive production of IL-1 beta plays a major role in certain inflammatory diseases, including SJIA and TRAPS. ACZ885 works by neutralizing IL-1 beta for a sustained period of time, thereby inhibiting inflammation.
Under the brand name Ilaris®, ACZ885 is approved in more than 60 countries, including the EU, US and Switzerland for the treatment of adults and children as young as four years with CAPS, a rare, lifelong, inflammatory disorder with debilitating symptoms. ACZ885 is also being studied in other diseases in which IL-1 beta plays a key role in causing inflammation, such as gouty arthritis and cardiovascular disease. ACZ885 is not approved for the treatment of SJIA or TRAPS. Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.
Disease: systemic juvenile idiopathic arthritis (SJIA)
Therapeutic area: Autoimmune diseases - Rare diseases
Country:
Trial
details: The pivotal Phase III study in patients with SJIA comprised of an open-label, single-arm active treatment period (Part 1) followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design period (Part 2)[1]. A total of 177 patients between the ages of >=2 and
Latest
news: Novartis has announced new data from a pivotal Phase III study with ACZ885 (canakinumab) in patients with systemic juvenile idiopathic arthritis (SJIA - a rare and serious autoinflammatory disease that usually start in childhood). The study met its primary endpoints,and the results will be presented on 7 June at the annual congress of the European League Against Rheumatism (EULAR 2012), in Berlin, Germany (Ruperto N, Brunner H, Quartier P, et al. Efficacy and safety of canakinumab, fully human anti-interleukin-1 beta antibody, in systemic juvenile idiopathic arthritis: Oral presentation at: The European League Against Rheumatism (EULAR) congress: June 6-9, 2012, Berlin, Germany).
In the Phase III study, 62% of SJIA patients treated with ACZ885 had inactive disease status at the end of the placebo-controlled period. In contrast, patients who had received ACZ885 treatment and were then randomized to receive placebo had a 32% rate of inactive disease at this time point. Disease inactivity is a rigorous definition of improvement, comprising absence of symptoms including: no active arthritis, no fever, no rheumatoid rash, as well as normalized blood markers normally associated with inflammation, such as ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein). In addition, one third (33%) of SJIA patients treated with ACZ885 were able to completely discontinue corticosteroids.
Data from this Phase III study support the safety and efficacy profile of ACZ885 in the study population. Side effects observed in this study were similar to those already seen for ACZ885\'s approved indication in CAPS (Cryopyrin-Associated Periodic Syndromes), including infections and neutropenia. Infections were the most common category of adverse event (AE) in both parts of the study. Cases of macrophage activation syndrome (MAS) were also reported.
The primary endpoints were to: a) assess if ACZ885 allows tapering of steroids in at least 25% of SJIA patients (Part 1); and b) demonstrate that time to flare is extended with ACZ885 vs. placebo (Part 2). Both primary endpoints were met, with 45% of patients successfully reducing their use of steroids within 28 weeks of commencing treatment with ACZ885 (p<0.0001). At this time point (end of Part 1), 31% of patients had inactive disease. Patients using ACZ885 were nearly three times (0.37 hazard ratio) less likely to suffer a new flare in Part 2. Only 22% of ACZ885-treated patients experienced a new flare, vs. 52% of patients on placebo during the study (p=0.0043). In Part 1 of the study (representing 58 patient years), 138 of 177 patients (78%) reported an AE, with the most common being nasopharyngitis, headache and cough. Serious adverse events (SAEs) were reported in 15 patients, with the most common being infections, MAS (four cases) or flare-associated events. Five SAEs led to discontinuation and one patient died of MAS[1]. During Part 2, AEs (the most common being arthralgia, cough, nasopharyngitis and pyrexia) were reported by 40 of 50 (80%) ACZ885-treated patients (vs. 35 of 50 [70%] placebo-after-ACZ885-treated patients); and six patients in each arm experienced one or more SAE, which mainly included infections, MAS and flare-associated events. Six patients, all in the placebo arm, discontinued the study due to AEs or SAEs during Part 2. One patient died from MAS after study discontinuation in the placebo group.
