Date: 2012-11-11
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 2012 Annual Scientific Meeting of the American College of Rheumatology (ACR)
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.
Disease: tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS)
Therapeutic area: Rare diseases - Inflammatory diseases
Country:
Trial
details: The ongoing Phase II, open-label, multicenter study investigating the efficacy and safety of ACZ885 in patients with active TRAPS involves 20 patients with a median age of 39 years (range, 7-78 years). In the first phase, patients received ACZ885 150 mg (or increased to 300 mg for those without complete or almost complete response by Day 8) every four weeks for four months. This was followed by a second, treatment withdrawal, phase of up to five months where the patients restarted ACZ885 treatment upon their first relapse. The third, ongoing, phase is a 24-month period involving open-label treatment every four weeks. The primary endpoint of the study is complete or almost complete response at Day 15.
Latest
news: Novartis has announced new data from two Phase II trials of ACZ885 (canakinumab), in patients with one of two rare syndromes characterized by periodic fevers. Key findings include reductions in disease attack frequency, maintenance of symptom relief, normalization of blood markers of inflammation, and quality of life improvements. Both rare orphan diseases, Familial Mediterranean Fever (FMF) and tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), are serious, inherited autoinflammatory diseases characterized by recurrent (periodic) fever attacks, rash, arthritis, and severe symptoms that can lead to fatal complications.
New data from the Phase II study in TRAPS showed that after rapid clinical remission and normalization of CRP and/or SAA, which was maintained with continued ACZ885 treatment, the median time to relapse after ACZ885 withdrawal was three months. Patients also regained their previous response upon re-dosing with ACZ885. Prior to study entry, patients experienced a mean of 10 attacks per year. When assessed during the initial four-month ACZ885 treatment period, patients experienced improvements in both physical and mental measures of quality of life.
Ninety percent of patients with TRAPS treated with ACZ885 experienced clinical remission (absent or minimal signs and symptoms of TRAPS) after one week of treatment, and two patients had their dose increased to 300 mg. After two weeks of treatment, 100% of patients achieved clinical remission and 95% of patients had achieved a complete or almost complete response, which was maintained until the end of treatment with monthly dosing.
Complete response was defined as clinical remission and normal CRP and/or SAA levels. Almost complete response was defined as clinical remission and >=70% reduction of baseline CRP and/or SAA. Clinical remission was maintained for all patients from Day 15 onwards in the four month treatment period, except for one patient with a relapse at Day 85 who subsequently responded to the scheduled ACZ885 dose.
All patients had at least one AE reported, and most AEs were mild in severity. Adverse events (AEs) observed in the studies were similar to those already seen for ACZ885\'s approved indication in Cryopyrin-Associated Periodic Syndromes (CAPS). Infections, mostly upper respiratory tract infections (URIs) were the most commonly reported category of AE in both the FMF and TRAPS studies. In the TRAPS study, two SAEs were reported: a URI that lasted two days and a severe disease attack with chest pain.
