Boston, MA—Belimumab is the first new drug for systemic lupus erythematosus (SLE) in more than 50 years and the first in its class to be approved by the US Food and Drug Administration (FDA).
The effectiveness and value of belimumab in the treatment of SLE was the subject of debate at the recent American College of Rheumatology 2014 Annual Meeting. On the pro side, a presenter indicated that belimumab met its primary end points in 2 large, pivotal, phase 3 trials and has gained FDA approval. On the con side, however, a researcher argued that other trials in SLE had lackluster findings, and the drug is expensive.
Belimumab Effective in SLE
Belimumab is a monoclonal antibody that binds the soluble form of B lymphocyte stimulator (BLyS), which is released from B cells, and is thought to reduce the number of abnormal
B cells in SLE. Belimumab is FDA-approved for the treatment of active, autoantibody-positive SLE in patients who are receiving standard therapy. Taking the pro position, Bevra H. Hahn, MD, Professor Emeritus at the University of California, Los Angeles, first discussed the mechanism of action (ie, destroying B cells). “This is the soluble form of BLyS, and inhibition of BLyS results in autoreactive B-cell apoptosis,” she told listeners.
More important than how it acts is whether it is effective, she continued. Two large, multicenter, prospective, randomized controlled studies compared belimumab plus standard therapy versus infused placebo plus standard therapy: BLISS-52 and BLISS-76. The studies included a total of 1684 patients with active SLE. The studies excluded patients who had received prior B-cell targeted therapy, or intravenous cyclophosphamide, and those who had active lupus involving the kidneys or central nervous system (CNS).
The studies showed a significant effect on severe flares, fatigue, and improved function and quality of life, and increased the number of patients who could reduce the dose of prednisone (ie, steroid-sparing effect). The studies included 2 patients who committed suicide, and there were serious infusion-related reactions.
Dr Hahn said that these findings influenced her decision not to initiate belimumab in patients who are severely depressed or expressing suicidal thoughts. Also, belimumab should not be given with other live vaccines. She deemed the cost of treatment, estimated at $28,000 to $35,000 annually, “acceptable” considering the therapeutic effects.
Belimumab Too Costly
David A. Isenberg, MD, Academic Director of Rheumatology at University College, London, UK, disagreed. First he presented findings from a cohort of 600 patients with SLE, mainly women, that he and his colleagues have been following for more than 30 years. Disease duration was more than 10 years and patients were of mixed ethnicity. In addition to the common manifestations of arthritis and rash, renal involvement was present in 30% of the cases and CNS involvement in 20%.
“These are the patients excluded from BLISS-52 and BLISS-76 [ie, renal involvement and CNS involvement],” he stated. Dr Isenberg finds it exciting that therapies like belimumab are targeted to the immune system based on better understanding of how it works. But does that translate to effectiveness and value, he asked.
He discussed 2 other studies of belimumab. One was a posthoc review of both BLISS trials and the other was a more extensive 52-week, placebo-controlled study called LBSL-2. LBSL-2 did not reach its primary endpoints: percent change in SELENA/SLEDAI (ie, measure of disease activity in SLE) from day 0 to week 24, and time to first mild/moderate or severe disease flare.
A post hoc review of both BLISS trials did not show a significant steroid-sparing effect of reduction in the risk of severe flares. Moreover, quality- of-life improvement was minimal or transient in both trials, he said.
Most objectionable, in his view, is the cost of treatment. “One third of patients continue on this drug at $30,000 a year, and it is not even working,” he concluded.