Novel Regimen Showing Promise, a First in Lupus Nephritis

Pam Harrison

November 21, 2016

CHICAGO — For patients with acute lupus nephritis, an induction regimen of voclosporin, a novel calcineurin inhibitor, plus mycophenolate mofetil (Cellcept) and oral corticosteroids is effective, according to early results from the AURA-LV study (NCT02141672).

"What is exciting about this study is that voclosporin is the first therapeutic agent ever to meet its primary end point in a global clinical trial for active lupus nephritis, said William Pendergraft, MD, from the University of North Carolina Health Care in Chapel Hill.

"And it met all its secondary end points as well, which is really exciting," he added.

One of the worst complications of lupus, a devastating inflammatory autoimmune disorder, is lupus nephritis, Dr Pendergraft explained during a news conference here at Kidney Week 2016.

Until now, "many of the trials, if not all, in lupus nephritis have been wildly unsuccessful," he explained.

AURA-LV Study

The AURA-LV study is designed to examine whether the addition of voclosporin to standard care will increase the speed of remission and overall remission rates.

"This was done in the presence of reduced exposure to steroids, which is very important aspect of this trial," Dr Pendergraft pointed out.

All 265 patients received mycophenolate mofetil 2 g plus low-dose oral corticosteroids (≤10 mg/day). In addition, patients in the low-dose group received voclosporin 23.7 mg twice daily, and patients in the high-dose group received voclosporin 39.5 mg twice daily.

The primary outcome of the trial was complete remission at 24 weeks, but the trial will continue out to 48 weeks, when the same end points will be reanalyzed.

It actually gives me goose bumps to think that we might finally have found a drug that can really help these patients.

During the first 24 weeks of the study, rescue medications were not allowed.

"Patients had what we thought was highly active disease," Dr Pendergraft pointed out. All met the American College of Rheumatology criteria for lupus, and all had biopsy-proven class 3, 4, or 5 lupus nephritis.

All patients also had proteinuria. Those with class 3 or 4 disease had at least 1.5 g of protein in the urine, and those with concomitant class 5 or pure class 5 disease had more than 2 g of protein in the urine.

Complete remission was defined as less than 0.5 g of protein in the urine, normal stable renal function, or a decrease in estimated glomerular filtration rate of less than 20% from baseline.

At 24 weeks, significantly more patients in the low-dose group than in the control group achieved complete remission (32.6% vs 19.3%; P = .045). In the high-dose group, 27.3% achieved complete remission.

In addition, all secondary end points — including partial remission, time to remission, time to partial remission, durability of remission, and decrease in extra renal activity — were met at 24 weeks.

Partial remission was achieved by 70% in the low-dose group, 66% in the high-dose group, and 49% in the control group.

No new safety signals were observed in this trial, Dr Pendergraft reported.

In each of the voclosporin groups, the rate of serious adverse events was about 25%, whereas in the control group, the rate was 16%.

"The nature of these adverse events was consistent with those observed in patients with highly active lupus nephritis," he explained. "And the overall safety profile of voclosporin is consistent with other immunosuppressant agents."

Of the 13 deaths during the study period, 11 occurred at sites that had compromised access to care.

These findings will help investigators plan and "de-risk" the phase 3 trial, which will be starting soon, Dr Pendergraft reported.

"We're all thrilled about these results. It actually gives me goose bumps to think that we might finally have found a drug that can really help these patients," he told Medscape Medical News. "It's very exciting, and the fact that patients in this study had really severe disease just makes it more so."

New Approach

Nephrologists are not using calcineurin inhibitors in patients with active lupus nephritis unless they are using them experimentally, said Gretchen Brandt, MD, from Kaiser Permanente in Washington, DC.

"This is a new area of medicine for this disease," she told Medscape Medical News. "There hasn't been a strong niche for active induction therapy using a calcineurin inhibitor."

But because voclosporin belongs to a well-known class of agents, nephrologists are already comfortable using them, Dr Brandt explained. This could be a bonus if voclosporin is approved for active lupus nephritis.

"It's also an oral medication and has a minimal side-effect profile," she added.

One advantage of voclosporin is that there is no need to adjust the dose on the basis of trough levels, Dr Pendergraft pointed out. And it has a better lipid profile than cyclosporine or tacrolimus, so is less likely to cause diabetes.

Unlike cyclosporine and tacrolimus," voclosporin has been specifically developed as a treatment for acute lupus nephritis," he explained. "There is great interest in bringing it to the market, and it has great benefits over the other two calcineurin inhibitors."

This study was funded by Aurinia Pharmaceuticals. Dr Pendergraft and Dr Brandt have disclosed no relevant financial relationships.

Kidney Week 2016: American Society of Nephrology Annual Meeting: Abstract HI-OR05. Presented November 19, 2016.

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