My Favorite Report at ACR2014: Sifalimumab for Lupus

December 9, 2014

(ACR2014) Another Rheumatology Network Editorial Board member weighs in: Christopher Collins MD saw reason for great encouragement in a report about an interferon-α blocker for systemic lupus erythematosus.

Khamashta M, Merrill JT, Werth VP et al. Safety and Efficacy of Sifalimumab, an Anti IFN-Alpha Monoclonal Antibody, in a Phase 2b Study of Moderate to Severe Systemic Lupus Erythematosus (SLE). Abstract #L4.

The cytokine family of type I interferons (IFNs), and especially the IFNα subtypes, have been implicated in systemic lupus erythematosus (SLE) pathogenesis.  It is observed that IFNα treatment is sometimes associated with lupus-like syndromes as well as the development of autoantibodies.

In patients with SLE, increased type I interferons levels are associated with greater disease activity, and genetic polymorphisms of several components of the IFN signaling pathway have been associated with an increased risk of lupus. Therefore, IFNα has been identified as a potential target for drug development in SLE.

In this phase 2b study looking at sifalimumab (anti-INFa) in patients with moderate to severe SLE, the primary endpoint of an improvement of the SRI-4 (SLE Responder Index – 4 point SLEDAI component improvement) greater than that in the placebo (standard of care) group was met at 52 weeks.

The ability to achieve a pre-defined primary endpoint in any lupus clinical trial is a feat which very few drugs have been able to achieve to date. This particular agent was able to demonstrate statistically and clinically meaningful improvement not only the primary endpoint of the SRI-4, but across several individual lupus disease manifestations as well as various degrees of disease severity.

This bodes well for not only for sifalimumab as it moves on to phase 3 testing, but keeps the hope alive that additional therapeutics are potentially on the horizon for our lupus patients.

Also, despite the failure of several high-profile drugs being tested in lupus which used the SRI as a primary endpoint, this study would suggest that, at least for now, the SRI remains a viable and meaningful tool for assessing disease improvement in clinical trial design.