Anifrolumab is an investigational, fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, inhibiting the activity of all type I IFNs, which play a central role in lupus, including IFN-alpha, IFN-beta, IFN-omega, and others.
New data were presented at the Annual European Congress of Rheumatology ( EULAR 2016 ), in London, U.K.
Results from the phase II MUSE trial in moderate to severe systemic lupus erythematosus have demonstrated that Anifrolumab reduces lupus disease activity across a wide range of clinical endpoints.
In the analysis of the primary endpoint, significantly more Anifrolumab-treated patients achieved an SLE Responder Index [ SRI(4) ] response at day 169 with sustained reduction of oral corticosteroids ( less than 10 mg/day and less than or equal to day 1 dose from day 85 to 169 ) compared to patients receiving placebo.
Even greater effect sizes were observed in the 75% of patients who had a high type I Interferon gene signature at baseline.
A new analysis of the phase II trial revealed a greater reduction in disease activity with Anifrolumab treatment versus placebo in individual organ domains frequently involved in lupus.
At week 52, changes in skin and joint activity ( the mucocutaneous and musculoskeletal domains ) were observed using the British Isles Lupus Assessment Group ( BILAG ) and SLE Disease Activity Index 2000 ( SLEDAI-2K ), with higher percentages of patients in the Anifrolumab-treated groups showing improvement.
Trends suggesting potential benefits were also observed in most of the other less frequently active organ domains, including cardiorespiratory, vascular, hematological and constitutional.
Anifrolumab treatment was well tolerated, and serious adverse events reported were similar across the three treatment groups. A dosage-dependent increase in herpes zoster cases ( placebo: 2.0%; 300 mg: 5.1%; 1000 mg: 9.5% ) and a greater number of events reported as influenza ( placebo: 2.0%; 300 mg: 6.1%; 1.000 mg: 7.6% ) were observed for patients receiving Anifrolumab.
The efficacy and safety of Anifrolumab were evaluated in a phase II, randomized, double-blind, placebo-controlled trial, known as MUSE, in which 305 adults with seropositive moderate to severe systemic lupus erythematosus receiving standard-of-care medications were randomized to receive intravenous ( IV ) Anifrolumab 300 mg or 1,000 mg Q4W or placebo every four weeks for 48 weeks.
Patients were stratified by SLE Disease Activity Index ( SLEDAI ) score, oral corticosteroid dosage, and IFN gene signature ( IFN high versus IFN low ) based on a 4-gene expression assay.
The trial met its primary endpoint of difference in the percentage of patients who achieved response as measured by the SLE Responder Index 4 ( SRI4 ) at day 169, along with a sustained reduction of oral corticosteroid use between day 85 and day 169.
The trial also met both secondary efficacy endpoints measuring responses at day 365. ( Xagena )
Source: AstraZeneca, 2016