American College of Rheumatology Annual Meeting

American College of Rheumatology Annual Meeting

Source:

Petri M, Rovin B. Session #6S113. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).

Disclosures: Petri reports receiving consulting fees from Alexion, Amgen, AstraZeneca, Aurinia, Axdev, Boston Pharmaceuticals, Emergent BioSolutions, Gilead, GlaxoSmithKline, Idorsia, IQVIA, Janssen, Kezar Life Sciences, Lilly, Merck EMD Serono, Momenta Pharmaceuticals, PPD Inc, Sanofi and UCB; and conducting contracted research for AstraZeneca, Aurinia, Exagen, GlaxoSmithKline, Janssen, Lilly and Thermo Fisher. Rovin reports being a medical or scientific advisor to AstraZeneca, Aurinia, Biogen, BMS, Caliditas, Janssen, Lilly, Galapagos, GSK, Genentech, MorphoSys, Novartis, Otsuka, Pfizer and Traverse.
November 06, 2021
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Great Debate pits belimumab against voclosporin as first-line therapy for lupus nephritis

Source:

Petri M, Rovin B. Session #6S113. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).

Disclosures: Petri reports receiving consulting fees from Alexion, Amgen, AstraZeneca, Aurinia, Axdev, Boston Pharmaceuticals, Emergent BioSolutions, Gilead, GlaxoSmithKline, Idorsia, IQVIA, Janssen, Kezar Life Sciences, Lilly, Merck EMD Serono, Momenta Pharmaceuticals, PPD Inc, Sanofi and UCB; and conducting contracted research for AstraZeneca, Aurinia, Exagen, GlaxoSmithKline, Janssen, Lilly and Thermo Fisher. Rovin reports being a medical or scientific advisor to AstraZeneca, Aurinia, Biogen, BMS, Caliditas, Janssen, Lilly, Galapagos, GSK, Genentech, MorphoSys, Novartis, Otsuka, Pfizer and Traverse.
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Although recent clinical data continue to expand possible treatment options for lupus nephritis, whether belimumab or voclosporin should be the first-line therapy remained hotly contested during the ACR’s annual Great Debate.

Michelle A. Petri, MD, MPH, director of the Hopkins Lupus Center at Johns Hopkins University, and Brad Rovin, MD, from the department of nephrology at the Ohio State University Wexner Medical Center, weighed in on whether belimumab (Benlysta, GlaxoSmithKline) or voclosporin (Lupkynis, Aurinia) is the more attractive option for lupus nephritis.

“In patients with a bad biopsy, with many bad prognostic markers, I don’t think we should be using mycophenolate alone,” Michelle Petri, MD, said in her presentation. “We should be very comfortable starting either a calcineurin inhibitor or belimumab right at the get-go.” Source: Adobe Stock

“We are all well aware of the huge unmet need of lupus nephritis,” Petri said. “In my cohort, in patients who develop nephritis in the first year, 20 years later, 20% are in end-stage renal disease.”

In her defense of belimumab, Petri laid out several considerations, including efficacy at 1 year and in the long-term; efficacy in class V disease; efficacy among Black patients, in non-renal parameters, in preventing organ damage and in preventing GFR reduction.

Michelle Petri, MD, MPH
Michelle A. Petri

Regarding early outcomes, Petri cited the pivotal phase 3 BLISS-LN trial investigating standard of care alone vs. standard of care plus belimumab in patients with lupus nephritis.

“The curves separate almost at the beginning of the trial,” she noted, regarding the primary endpoint of renal response as assessed by creatinine of less than 700 mg. “The delta is actually bigger just before and after the 52-week mark.”

While Petri stressed that comparing clinical trials with different study designs and outcome measures is “not fair,” she highlighted a similar study investigating voclosporin. She noted that, in comparing the two drugs, all subsets favored belimumab except among patients with pure class V disease. While voclosporin demonstrated a stronger result, belimumab was also effective. “In time to renal event or death, by 8 weeks, the curves separate in favor of belimumab with a very nice P value,” she said.

In another comparison of outcomes for the two drugs, Petri looked at time to first renal flare in Black patients. While the delta for this outcome failed to reach statistical significance in the belimumab study, it did reach statistical significance among the 45 Black patients included in the voclosporin trial.

Turning to extra renal outcomes, Petri noted that in the Accelerating Medicines Partnership Lupus Network study, 30% of patients had these complications. “The benefit of belimumab beyond the kidney has been proven in the original phase 3 trials,” she said.

If there was another important take-home message for Petri, it pertains to the capacity of belimumab to stem the tide of organ damage. “It has been shown in novel analyses to prevent time to organ damage progression,” she said, highlighting findings from the BLISS trial.

Turning to GFR outcomes, Petri once again compared belimumab and voclosporin trials. She noted that while the curve for voclosporin in this outcome runs slightly below the standard of care, belimumab protected GFR “virtually from about 3-4 months.”

In defending voclosporin, Rovin framed the discussion in terms of five key arguments. The first is that the two key clinical trials that led to the approval of voclosporin demonstrated one clear outcome: “The combination of voclosporin plus mycophenolate is more effective than mycophenolate alone,” he said.

Brad Rovin

These studies also offered another critical consideration for rheumatologists treating lupus nephritis, namely that patients treated with the combination of voclosporin and mycophenolate require “much less glucocorticoid” than those treated with mycophenolate alone. “This translates into fewer adverse events,” he said. “And, maybe more importantly, adherence to these regimens. Certainly, adherence to glucocorticoids is a big issue.”

For his third argument, Rovin piggybacked off the point made by Petri that voclosporin has shown improved efficacy in Black patients. He added that the drug has demonstrated strong outcomes in patients of Hispanic and non-Hispanic ethnicity. “The third argument in favor of voclosporin is that the combination is effective in patients of diverse racial and ethnic backgrounds,” he said. “That is relevant to the treatment of lupus and lupus nephritis, as you know.”

His fourth argument addressed the speed with which voclosporin can reduce proteinuria. “Rapid response is actually kidney protective overall,” Rovin said. “Time is nephrons in these inflammatory diseases.”

The final point Rovin offered pertained to safety parameters. He noted that in the key trials that led to the approval of the drug, pooled adverse event rates showed no difference between voclosporin and controls in terms of serious events or infections.

“There was an imbalance of deaths in the phase 2 trial but not in the phase 3 trial,” he said, noting that the increase was likely not dose related. However, he suggested that “extraneous circumstances," including drug adherence and access to care, may have led to this outcome.

Ultimately, both Petri and Rovin believe that while there are specific points that argue for belimumab or voclosporin, there is room for both drugs in managing the diverse patient population of lupus nephritis.

“It is time to change our paradigm,” Petri said. “In patients with a bad biopsy, with many bad prognostic markers, I don’t think we should be using mycophenolate alone. We should be very comfortable starting either a calcineurin inhibitor or belimumab right at the get-go.”