Novartis announced positive results of the first pivotal phase III trial of ACZ885 (canakinumab) in patients with systemic juvenile idiopathic arthritis (SJIA), a rare and serious childhood auto-inflammatory disease. The results, presented at the 2011 European Pediatric Rheumatology Congress in Bruges, Belgium, showed all primary and secondary endpoints of the study were met.

Most ACZ885 patients (83.7%) experienced at least a 30% improvement in symptoms vs. 9.8% for placebo (p<0.0001) and a third of ACZ885 patients (32.6%) achieved a 100% improvement vs. 0% for placebo (p=0.0001). ACZ885 is an investigational, fully human monoclonal antibody that neutralizes interleukin-1 beta (IL-1 beta), which is a key driver of inflammation in SJIA.

"These data suggest that ACZ885 could become an important treatment option for children living with SJIA, the most difficult-to-treat and severe form of juvenile arthritis, potentially transforming their lives," said Professor Pierre Quartier, MD, one of the study investigators and Pediatric Rheumatologist Pediatric Immuno-Haematology and Rheumatology Unit, Necker-Enfants Malades Hospital, Paris, France. "ACZ885 provided rapid and long-lasting symptom relief by targeting interleukin-1 beta, a key inflammatory mediator of the disease."

SJIA affects less than one child per 100,000. It is called 'systemic' because the inflammation affects the whole body, as well as most of the joints. The condition is characterized by potentially life-long and recurrent arthritis flares, which can involve skin rash, daily spiking fever, joint pain and swelling. These young patients can face joint destruction and growth retardation, with serious developmental and psychological consequences.

In this study, patients were measured according to the adapted American College of Rheumatology (ACR) Paediatric criteria, which includes absence of fever. The ACR criteria are regularly used to assess the success of treatments in SJIA.

"These results are a positive development for patients suffering from this very severe auto-inflammatory condition," said David Epstein, Head of the Pharmaceuticals Division of Novartis. "We are committed to investigating ACZ885 in a range of inflammatory diseases where interleukin-1 beta plays a key role and high unmet medical needs exist."

Therapies traditionally used to treat SJIA can only partially mitigate symptoms and do not prevent the long-term damage of the disease. Long-term steroid use designed to treat SJIA symptoms can also contribute to slowed growth and delayed puberty.

The results of a second pivotal phase III trial, aimed at determining whether ACZ885 can extend the time to next flare and reduce or eliminate corticosteroid use, will be presented later this year. Worldwide regulatory submissions for ACZ885 in SJIA are planned for 2012.

The study was a phase III, 4-week, randomized, double-blind, placebo-controlled study involving 84 patients between the ages of 2 and 19 years, with active SJIA. Patients were treated with either a single subcutaneous (s.c.) dose of ACZ885 (4 mg/kg, up to 300 mg) or placebo.

The primary endpoint was the proportion of patients achieving the adapted ACR Paediatric 30 criteria, demonstrating a 30% improvement in at least three of the six variables, from baseline at Day 15. The six variables included physician's assessment of disease activity, parent's or patient's assessment of overall well-being, functional ability, number of joints with active arthritis, number of joints with limitation of motion and C-reactive protein, a laboratory measure of inflammation.

Secondary endpoints included the proportion of patients achieving the adapted ACR Paediatric 50, 70, 90 and 100 criteria, demonstrating a 50%, 70%, 90% and 100% improvement in at least three variables from baseline at Day 15 and 29.

ACZ885 was generally well tolerated. During the study, 55.8% of patients experienced adverse events (AEs), including infections, with ACZ885 vs. 39% with placebo. Serious adverse events (SAEs), including infections, were reported for two patients for ACZ885 vs. two for placebo. These did not lead to discontinuation and were resolved without complications.

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. ACZ885 works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation.

Under the brand name Ilaris, ACZ885 is approved in more than 50 countries, including the EU, US and Switzerland for the treatment of adults and children as young as four with Cryopyrin-Associated Periodic Syndromes (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. Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.