The FINANCIAL -- Novartis
announced new data from two trials with ACZ885 ; a
pivotal Phase III study in patients with systemic juvenile idiopathic
arthritis, and a Phase II study in patients with tumor necrosis
factor receptor-associated periodic syndrome.
SJIA and TRAPS are both rare and serious autoinflammatory diseases that usually start in childhood.
Both studies met their 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.
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 and CRP. According to Novartis, in addition, one third (33%) of SJIA patients treated with ACZ885 were able to completely discontinue corticosteroids.
The aim of SJIA therapy is to suppress systemic inflammation and induce disease inactivity. Long-term corticosteroid use in children is associated with potentially serious adverse effects, including Cushing syndrome, growth suppression, and osteoporosis.
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, 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 were also reported.
"In clinical practice, our aim is to help children with SJIA lead a normal life. It is encouraging to see many patients become free of SJIA symptoms in this trial," said Prof Alberto Martini, Professor of Pediatrics at the University of Genoa and Head of Pediatric Rheumatology at the G. Gaslini Research Institute, Italy. "It is also positive that a third of patients achieved sufficient symptom control with ACZ885 to allow them to completely discontinue corticosteroid therapy."
In the Phase II study, 90% of TRAPS patients treated with ACZ885 experienced clinical remission after only one week of treatment. Clinical remission included a clinically significant improvement of disease symptoms, as assessed by the treating physician. After two weeks of treatment, 95% of patients with TRAPS treated with ACZ885 had achieved a complete or almost complete response, which was maintained until the end of treatment with monthly dosing.
Side effects observed in this study were similar to those already seen for ACZ885's approved indication in CAPS. Infections, mostly upper respiratory tract infections (URIs), were the most commonly reported category of AE.
"It is encouraging to witness that targeting interleukin-1 beta with ACZ885 can result in such marked improvement of symptoms in patients with these rare and debilitating conditions, such as SJIA and TRAPS", said John Hohneker, Head of Development for Integrated Hospital Care for the Pharmaceuticals Division of Novartis. "We are committed to investigating new treatments that can address the existing unmet medical need in immune-mediated diseases, no matter how rare some of these conditions may be."
SJIA is a rare systemic interleukin-1 beta -mediated autoinflammatory disease characterized by daily spiking fevers, rash, chronic pain, and arthritis that may result in joint destruction, functional disability and impaired growth. Patients can also suffer enlargement of their liver and spleen, as well as inflammation of the lining of their organs. SJIA affects less than one child per 100,000.
MAS is a known, potentially fatal condition associated with SJIA that is characterized by liver abnormalities, bleeding disorders, central nervous system dysfunction and multiple organ failure. Approximately 10% of SJIA patients are diagnosed with MAS, some of whom suffer repeated episodes.
TRAPS is a rare auto-inflammatory disease that can affect both children and adults. This genetically inherited disease is characterized by long and intermittent attacks that can involve fever, rash, abdominal pain, conjunctivitis, severe skin infection, inflammation around the eyes and severe joint pain.
Amyloidosis is a serious complication of TRAPS and is estimated to occur in 25% of patients. This long-term complication involves the production of SAA during inflammation, and can lead to liver and/or kidney failure. In some instances, amyloidosis can be fatal.
There are currently no approved treatments for TRAPS. While nonsteroidal anti-inflammatory drugs, steroids and colchicine have been shown to relieve some symptoms, there can be problems with limited and intermittent efficacy, in addition to the side-effects of long-term steroid use, particularly in children.