Long-term safety of Lupkynis for SLE confirmed in AURORA trial
No signs of kidney toxicity seen in lupus patients in 18-month study
Over 18 months, the approved therapy Lupkynis (voclosporin) lessened inflammation and prevented further kidney damage in systemic lupus erythematosus (SLE) patients with active lupus nephritis, without any signs of kidney-related toxicity seen with similar treatments.
New top-line data show participants in the Lupkynis treatment arm of the now completed Phase 3 AURORA trial (NCT03021499) had similar kidney biopsy (histologic) findings as those in the active control arm receiving mycophenolate mofetil, an immunosuppressant sold under the brand name CellCept, and low-dose steroids alone.
These results contrast with the well-known kidney-related side effects — known as nephrotoxicity — associated with similar medicines, such as cyclosporine and tacrolimus. Known as calcineurin inhibitors (CNIs), these therapies block a protein called calcineurin, reducing inflammation and protecting kidney cells.
Lupkynis is a next-generation CNI with higher potency and a different metabolic profile. These features allow the medication to be given at lower doses, and potentially improve its overall tolerability compared with cyclosporine and tacrolimus.
“The lack of histologic evidence of CNI nephrotoxicity and the absence of progression of chronic kidney damage after approximately 18 months of treatment further strengthen the overall evidence supporting the long-term safety of Lupkynis in [lupus nephritis] patients,” Brad Rovin, MD, professor of nephrology at the Ohio State University Wexner Medical Center, said in a press release from Aurinia Pharmaceuticals. Aurinia is Lupkynis’ developer and the sponsor of the AURORA trial.
According to Greg Keenan, MD, chief medical officer at Aurinia, this result “further differentiates the safety of this second-generation treatment from the legacy, first generation CNIs.”
Lupus nephritis, a type of kidney inflammation, is one of SLE’s most frequent and severe complications.
By blocking calcineurin, CNIs like Lupkynis work by suppressing the inflammatory activity of immune T-cells, while stabilizing the molecular support that gives kidney cells their structure.
Data from AURORA and its extension study, AURORA 2 (NCT03597464), supported Lupkynis approvals in the U.S., the U.K., and Europe. Results showed that Lupkynis, when given alongside mycophenolate mofetil and low-dose steroids, helped maintain stable kidney function.
The lack of … evidence of [toxicity] and the absence of progression of chronic kidney damage after approximately 18 months of treatment further strengthen the overall evidence supporting the long-term safety of Lupkynis in [lupus nephritis] patients.
Now, biopsy kidney samples were collected over 18 months from 16 participants in the Lupkynis arm and from 10 in the control arm of AURORA. Pre-treatment (baseline) and follow-up tissue analyses were conducted to assess activity scores, a measure of active inflammation, and chronicity scores, a measure of irreversible kidney damage.
Compared with baseline, activity scores for both Lupkynis and control groups showed similar improvement, while chronicity scores remained stable over 18 months in both groups.
“We are encouraged by these results,” Keenan said, adding, “Seeing similar improvement in the activity scores and absence of change in the chronicity scores with the Lupkynis treated patients as compared to those on MMF and low dose steroids alone strengthens the totality of the evidence supporting the long-term efficacy and safety of Lupkynis.”
According to Aurinia, detailed data from these analyses will be presented at the Congress of Clinical Rheumatology meeting, to be held May 4-7.
Approved in the U.S. in January 2021 and the EU in September 2022, Lupkynis is the first treatment indicated for adults with active lupus nephritis.