Date: 2014-11-17
Type of information: Presentation of results at a congress
phase: 2b
Announcement: presentation of results at the American College of Rheumatology (ACR) 2014 Annual Meeting in Boston, MA
Company: Medimmune (USA - MD) global biologics arm of AstraZeneca (UK)
Product: sifalimumab
Action
mechanism: Sifalimumab (formerly MEDI-545) is an investigational human monoclonal antibody that targets IFN-α subtypes, inflammatory cytokines in the body known to play a role in the development of SLE. Previous studies have shown that elevated levels of IFN-α are correlated with more severe disease activity in SLE patients and early studies of sifalimumab have demonstrated that this agent inhibits signaling of interferon alpha subtypes.
Disease: moderate to severe systemic lupus erythematosus
Therapeutic area: Autoimmune diseases
Country:
Trial details:
Latest
news: * On November 17, 2014, MedImmune, the global biologics research and development arm of AstraZeneca, announced it will be presenting positive data from a Phase IIb study on sifalimumab, a novel monoclonal antibody targeting interferon being investigated for treatment in patients with moderate to severe systemic lupus erythematosus (SLE or lupus), at the American College of Rheumatology (ACR) 2014 Annual Meeting in Boston, MA. The study met its primary endpoint of percentage of subjects that responded as measured by the SLE Responder Index (SRI-4) at week 52. In addition, statistically significant improvements were seen in multiple other clinical measures of disease activity. Study results will be presented in a late-breaking oral presentation on Tuesday, November 18 at 3:15 pm. The efficacy and safety of sifalimumab were assessed in a Phase IIb, randomized double-blind placebo-controlled study in subjects with moderate to severe SLE. The study evaluated 431 patients receiving sifalimumab at monthly doses of 200, 600 or 1200 mg, plus their current standard of care, or placebo along with standard of care. The results show that the percentage of patients achieving improvement as measured by the SLE Responder Index (SRI-4) at week 52 was significantly higher for sifalimumab at all doses versus placebo plus standard of care (placebo/SOC, 45.4%; 200 mg, 58.3%; 600 mg, 56.5%; 1200 mg, 59.8%). Sifalimumab targets interferon-α subtypes, inflammatory cytokines in the body known to play a critical role in the pathogenesis of SLE. The Phase IIb study on sifalimumab is the first to demonstrate efficacy in moderate to severe systemic lupus patients across multiple endpoints with an anti-interferon molecule. Most commonly reported adverse events (AEs) were similar across groups including worsening SLE (sifalimumab 30.0% vs placebo 34.3%), urinary tract infection (17.6% vs 13.9%) and headache (13.3% vs 13.9%). Serious AEs were reported in 18.3% (sifalimumab) vs 17.6% (placebo) of subjects. An increase in subjects reporting Herpes zoster was seen in subjects receiving sifalimumab, particularly in the 1200 mg group (placebo, 0.9%; 200 mg, 4.6%; 600 mg, 3.7%; 1200 mg, 8.4%). The trial shows robust responses across multiple endpoints, as evident by greater differences relative to placebo both with SRI-4 and more stringent response criteria such as SRI-6, 7 or 8 with statistically significant effects for all sifalimumab groups at week 52. Furthermore, in a different composite disease activity measure, the BILAG-based Combined Lupus Assessment (BICLA), improvements over placebo were shown in all three dose groups, with a statistically significant effect for 1200 mg group at 52 weeks. Improvements in organ-specific outcomes also seen: The study also shows positive results in clinically important organ-specific outcome measures including skin (rash) and joint involvement (swollen and tender joints). Skin rashes were assessed by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), with the study demonstrating that a significantly higher percentage of subjects with moderate to severe skin involvement had a ≥4 point decrease in CLASI on sifalimumab 200 mg and 1200 mg (72.7%, 73.1%) versus placebo/SOC (48.6%) at 52 weeks. Furthermore, a statistically significant higher percentage of patients with moderate to severe joint involvement had a joint response (50% reduction in the number of swollen and tender joints) for all three doses of sifalimumab compared with placebo/SOC at 52 weeks.
