Lupkynis helps protect kidneys with lupus nephritis and high proteinuria

Pooled trial data favor use with background therapy for at-risk patients

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by Lindsey Shapiro |

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Lupkynis (voclosporin) combined with background lupus treatments better preserved kidney function among a subgroup of lupus nephritis patients with particularly high protein levels in the urine (proteinuria) compared with background therapy alone.

Notably, these benefits were observed regardless of patients’ baseline demographic or clinical characteristics, and they were generally consistent with trial analyses involving the broader lupus nephritis population, according to the therapy’s developer, Aurinia Pharmaceuticals.

That’s according to pooled analyses from two clinical trials presented at the European Congress of Rheumatology 2023, held May 31 to June 3 in Milan, Italy. Findings were in the poster (details on page 273), titled “Efficacy and Safety of Voclosporin Across Patient Subgroups With Proteinuria ≥2 MG/MG: An Integrated Analysis Of The AURA-LV and AURORA 1 Studies.”

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“We are pleased to present these findings that further support the efficacy and safety of a voclosporin-based treatment regimen across diverse [lupus nephritis] patient populations,” Greg Keenan, MD, chief medical officer at Aurinia, said in a company press release.

“These findings further differentiate Lupkynis, a next-generation CNI [calcineurin inhibitor], from legacy, first-generation CNIs,” Keenan said.

Lupus nephritis is a serious complication of lupus marked by kidney damage and inflammation. When the kidneys are damaged, protein leaks into the urine. High proteinuria is an indicator of kidney dysfunction and more active lupus nephritis, and it is associated with more severe kidney damage and poorer long-term outcomes.

“There remains the need for safe and effective therapies for patients with high proteinuria, especially given that monoclonal antibody therapies have demonstrated limited efficacy in LN patients with moderate to high proteinuria,” said Emily Littlejohn, a rheumatologist at the Cleveland Clinic in Ohio and the study’s lead author.

Lupkynis is approved in the U.S., European Union, and the U.K. as an oral treatment for adults with active lupus nephritis when combined with background immunosuppressant therapy, including mycophenolate mofetil and corticosteroids.

It works by blocking the activity of a protein called calcineurin — a mechanism thought to reduce inflammation and stabilize kidney cells. Lupkynis was developed by Aurinia, which is partnering with Otsuka Pharma to market the therapy outside the U.S.

Lupkynis was evaluated in the placebo-controlled Phase 2 AURA-LV (NCT02141672) and the Phase 3 AURORA (NCT03021499) trials. A pooled analysis from those trials indicated that Lupkynis, given on top of standard therapy, led to more stable kidney function than background therapy alone, regardless of patients’ demographics.

Both trials enrolled adults with lupus nephritis and proteinuria levels at or above 1.5 g/g. That measurement refers to grams of protein per gram of creatinine, a waste product, in the urine. Known as the urine protein creatinine ratio, or UPCR, it is a standard way of assessing for proteinuria in the clinic. For reference, a normal UPCR value would be at or below about 0.2 g/g.

Participants in either trial received 23.7 mg of Lupkynis or a placebo twice daily alongside mycophenolate mofetil and corticosteroids for up to about a year. Corticosteroid doses were tapered during the trial.

CRR more likely for trial patients on Lupkynis plus background therapy

In the recent analysis, researchers aimed to better understand the effects of Lupkynis in the subgroup of patients with especially high proteinuria, or a UPCR at or above 2 g/g.

Of the 268 trial patients treated with Lupkynis, 217 had a starting UPCR at or above the cutoff value, with a mean of 5.1 g/g. Among the 266 patients randomized to a placebo, 215 met the criteria, with a mean UPCR value of 4.6 g/g.

After a year of treatment, patients given Lupkynis saw a 3.8 g/g decline in UPCR, a significant difference from those in the placebo group, who saw their UPCR drop by 3.1 g/g.

To look at the treatment’s broad effectiveness, researchers assessed how many people in each group achieved a complete renal response (CRR) — a composite measure that essentially indicates a person’s kidney function is in a normal range or stable. Specifically, a CRR was defined as a UPCR at or below 0.5 g/g and stable renal function, with low doses of steroids and no need for rescue medications.

A significantly greater proportion of Lupkynis-treated patients achieved CRR after a year of treatment (41%) compared with the placebo group (21.9%), with a nearly 2.5 times higher odds of achieving a response on Lupkynis.

Response rates were highest among patients in the least severe kidney biopsy class, meaning those with less kidney damage. Still, response rates were numerically greater across Lupkynis-treated patients, regardless of biopsy classification.

Likewise, Lupkynis was associated with better responses compared to a placebo regardless of sex, age, ethnicity, and kidney function at the study’s start. Rates of side effects were similar in both groups and stable over a year of treatment.

Altogether, the findings are “clinically relevant given the lack of safe and effective therapies for patients with high proteinuria,” the researchers wrote.