New England Journal Of Medicine, a weekly medical journal, publishes medical research findings, review articles, and editorial opinion on various topics of importance to biomedical science and clinical practices. The company focuses on internal medicine and specialty areas, including allergy/immunology, cardiology, endocrinology, gastroenterology, hematology, kidney diseases, oncology, pulmonary diseases, rheumatology, HIV, and infectious diseases. It also offers current issues, and an online archive through browsing, searching, or collections by diseases. In addition, the company provides subscriber services include PDA content access, PowerPoint downloads, and continuing medical education....
860 Winter Street
Waltham, MA 02451 1413
New England Journal Of Medicine Publishes the Results of Two Phase III Trials
Dec 19 12
New England Journal Of Medicine published the results of two Phase III trials, and both show ACZ885 (canakinumab) provided substantial symptom relief in young patients with systemic juvenile idiopathic arthritis (SJIA).(1) In addition, ACZ885 delayed disease flare recurrence and allowed patients to substantially reduce or discontinue use of corticosteroids.(1) ACZ885 is a Novartis compound being studied for use in SJIA, a rare, disabling and potentially fatal autoinflammatory disease, characterized by spiking fever, rash, and arthritis that may result in joint destruction, functional disability and impaired growth. In beta-SPECIFIC 1 (trial-1), 84% of SJIA patients treated with ACZ885 experienced at least a 30% improvement in symptoms compared to 10% for placebo after 15 days of treatment, which was sustained after 29 days (p<0.001).(1) In beta-SPECIFIC 2 (trial-2), 45% of ACZ885-treated patients who were prescribed corticosteroids at study entry were able to substantially reduce their use of steroids, and one third of patients completely discontinued steroids.(1) Additionally, ACZ885-treated patients were nearly three times less likely to experience a new flare, with 74% of ACZ885-treated patients remaining flare-free compared to 25% with placebo (p=0.003) (Kaplan-Meier estimate). Data from the Phase III program of ACZ885 in SJIA form the basis for worldwide regulatory submissions. In the EU, regulatory submission was completed in November 2012. US regulatory submission is also on track. Both studies explored multiple secondary endpoints.(1) During the double-blind, single-dose beta-SPECIFIC 1 study, a third of ACZ885 patients (33%) experienced inactive disease -- which includes a complete absence of disease signs and symptoms -- vs. 0% for placebo at Day 15.(1) This was sustained until the end of the study (Day 29, 30% of patients for ACZ885 vs. 0% for placebo).(1) At the end of 32 weeks of open-label ACZ885 treatment in beta-SPECIFIC 2, 31% of patients attained inactive disease status, and 62% of patients who continued to receive ACZ885 had inactive disease at the end of the study.(1) In contrast, patients who had received ACZ885 treatment and were then randomized to receive placebo had a 34% rate of inactive disease at this time point.(1) At the end of beta-SPECIFIC 2, 82% of patients met the adapted JIA American College of Rheumatology Pediatric (JIA ACR) 70 response criteria with ACZ885, vs. 62% for placebo-after-ACZ885-treated patients.(1) In beta-SPECIFIC 1, 56% of patients experienced adverse events (AEs) with ACZ885 vs. 39% with placebo.(1) In Part I of beta-SPECIFIC 2, 78% of patients had a reported AE and during Part II, AEs were reported for 80% of ACZ885-treated patients (vs. 70% of placebo-after-ACZ885-treated patients).(1) Serious adverse events (SAEs) that were most frequently reported were flares of SJIA, infections and macrophage activation syndrome (MAS).(1) MAS occurred in seven patients across beta-SPECIFIC 1 and beta-SPECIFIC 2, and infections were more frequent with ACZ885 than placebo. Beta-SPECIFIC 1: The Phase III, 4-week, randomized, double-blind, placebo-controlled study involved 84 patients between the ages of 2 and 19 years with active SJIA.(1) Patients were treated with either a single subcutaneous (s.c.) dose of ACZ885 (4 mg/kg, up to 300 mg) or placebo.(1). Beta-SPECIFIC 2: The Phase III, two-part study had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II.(1) A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study.(1) Some of these patients had previously participated in the beta-SPECIFIC 1 trial. In Part I, patients received a s.c. dose of ACZ885 (4 mg/kg, up to 300 mg) every 4 weeks.