What’s On the Horizon for SLE?
The prescription of drugs for systemic lupus erythematosus (SLE) market will likely grow significantly in the coming years because of important research related to an unmet need, patients who are not satisfied with their treatment, and many promising drugs in the pipeline.1,2 Some analysts indicate that that expenditures for drugs for lupus totaled $1.1 billion in 2008, with a projected increase to $1.6 billion in 2015. There are three new biologic products in phase III development—atacicept, belimumab, and ocrelizumab/ RG1594. There are others, such as epratuzumab, that are in phase II development.
Belimumab (Benlysta, formerly Lymphostat-B) is an intravenous B-lymphocyte stimulator (BLyS) –specific inhibitor to treat SLE.3 The agent is a human monoclonal antibody that specifically recognizes and inhibits the biological activity of BLyS, which is a naturally occurring protein needed in order for B-lymphocytes to develop into mature plasma cells. In SLE, elevated BLyS levels are thought to contribute to autoantibody production because the levels of autoantibodies can correlate with disease activity. Results of the phase III trial BLISS 52, a 52-week, double-blind, placebo-controlled, multicenter superiority trial, suggested that belimumab plus standard of care can reduce SLE disease activity. A significant improvement in patient response was seen at Week 52 in belimumab-treated patients compared with placebo-treated patients. A delayed time to the first SLE flare and lowering the risk of severe SLE flares were also more favorable with belimumab treatment.4 Belimumab was generally well tolerated, with an adverse event rate similar to placebo. The most common adverse effects were headache, arthralgias, upper respiratory infections, urinary tract infections, and influenza. No malignancies were reported. An additional phase III trial (BLISS 76), a 76-week study carried out with the same study design as BLISS 52, is underway to replicate the results of BLISS 52. There were more than 800 patients enrolled in this latter study.
Atacicept is a subcutaneously administered recombinant fusion protein of the TACI receptor and human immunoglobulin G. This agent can bind BLyS as well as a proliferation inducing ligand called APRIL. These characteristics make the agent a potent stimulator of B-cell maturation, propagation, and survival.5 The makers of atacicept are currently enrolling patients in a study to evaluate its ability to reduce SLE flares when given twice weekly for four weeks, followed by once weekly up to a year.6
Ocrelizumab is a humanized anti-CD20 monoclonal antibody being studied for the management of lupus nephritis.7 A phase III efficacy and safety study of ocrelizumab in combination with corticosteroids plus one or two immunosuppressant regimens (SOC) compared to SOC alone in SLE patients with Class II or IV nephritis is ongoing.8 The estimated date for primary completion of this trial is January 2013. Finally, epratuzumab, in a 12-week phase IIb trial in 227 SLE patients, showed a 25% treatment advantage over placebo for disease activity. This agent is a humanized anti-CD22 monoclonal antibody that potentially modulates B-cell activity.9