The Great Debate: Belimumab vs. Voclosporin in Lupus Nephritis

“Why is this important? The FDA [U.S. Food & Drug Administration] has now accepted GFR trajectory as a surrogate for end-stage kidney disease in trials,” she said. “Why are we treating the patient? We’re trying to prevent end-stage kidney disease.”

Patients in the voclosporin trial tended to see a reduction in GFR, but Dr. Rovin noted the curve remained flat, without a continuing decline over time. This is the result of kidney blood flow changes brought on by the therapy, he said.

“The reason the GFR declines is that glomerular perfusion is slightly decreased by the calcineurin inhibitor,” he said. “That decrease in intraglomerular pressure also tends to result in a benefit in terms of glomerular sclerosis over the long term.”

3. Rapid Proteinuria Decrease from Voclosporin

Dr. Rovin

The voclosporin trial showed proteinuria began to drop in a matter of days, which Dr. Rovin said is likely due to the drug’s protective effects on podocytes, the epithelial cells that coat glomerular capillaries.² Early remission tends to lead to better preservation of kidney function over time, he said.

“Time is nephrons,” Dr. Rovin said.

4. Efficacy in African Americans

Although the primary efficacy renal response favored belimumab over placebo in the pivotal trial in this subset, the result wasn’t statistically significant. Voclosporin’s response rate was statistically significant among African Americans, however.

Dr. Petri said this could have to do with the study’s entry criteria. An MMF dose of up to 3 g was allowed in the belimumab trial, but the limit was 2 g in the voclosporin trial. In her experience, African Americans tend to do better with the 3 g dose, she said. This methodology difference could help explain the belimumab result.

“The delta is always going to be affected by how good the comparison group is,” she said.

5. Safety

Dr. Petri said the data on safety favors belimumab in nearly every category (i.e., nephrotoxicity, infection, cardiovascular risk factors, malignancy and drug-drug interactions), and she suggested there might be adherence advantages because the infusions allow for an objective measure of adherence. 

Dr. Rovin offered a caveat in interpreting this observation: “[Although] Dr. Petri presented a side-effect profile that may not have appeared to be as clean as belimumab, one of the issues with that is most of these side effects are coming from the transplant literature, where the calcineurin inhibitors are literally lifelong medications as long as you have the allograft. So the expectation, at least in my mind, is that we’re not going to be using voclosporin on a long-term basis.”