Type B part of EQUALISE trial recruiting SLE patients with active lupus nephritis
by Lindsey Shapiro | October 10, 2022
Equillium’s investigational antibody-based treatment, itolizumab (EQ001), led to significant reductions in urine protein levels — a marker of kidney dysfunction — in systemic lupus erythematosus (SLE) patients with active lupus nephritis, according to an interim analysis from the type B portion of the Phase 1b EQUALISE clinical trial.
“We are very encouraged by the interim data from the [lupus nephritis] portion of the EQUALISE study,” Bruce Steel, Equillium CEO, said in a press release, adding the data “adds to our conviction in the clinical activity of itolizumab and the potential to be an impactful therapy for patients with lupus nephritis.”
The type B portion of EQUALISE (NCT04128579) is still recruiting SLE patients with active lupus nephritis, ages 18–75, at sites in the U.S., India, and Poland.
“We look forward to continuing to enroll patients in the Type B portion of the EQUALISE study and anticipate sharing topline data in mid-2023. In parallel, we are engaged with key opinion leaders to prepare for later stage development that we expect can support potential product registration,” Steel added.
Lupus nephritis is a common SLE complication that occurs when the self-reactive antibodies that cause SLE damage the kidneys. As a result, the kidneys become inflamed and their function impaired; in some cases, this can lead to kidney failure.
Treatment usually involves medications to reduce inflammation, including corticosteroids, which can come with significant side effects and are not always effective.
“Despite recently approved therapies, 60% of lupus nephritis patients are failing to achieve a complete response at 12 months, highlighting the need for new medicines with differentiated mechanisms,” Steel said.
Itolizumab Granted FDA Fast Track Designation as Potential Treatment for Lupus Nephritis
Itolizumab targets the CD6 receptor on the surface of immune T-cells that help drive inflammation in SLE. CD6 and the protein that binds to it, called ALCAM, are at higher-than-normal levels in the kidneys of people with lupus nephritis, and are associated with disease activity. ALCAM also is increased in patients’ urine, particularly in those with active disease.
Itolizumab effectively blocks CD6’s interaction with ALCAM, and in doing so is thought to prevent the unwanted activity of T-cells, easing inflammation, and preventing further kidney damage.
EQUALISE was initiated in 2019 to evaluate the therapeutic potential of itolizumab in up to 55 SLE patients with and without active lupus nephritis. The type A portion of the trial evaluated the safety of five itolizumab doses — 0.4, 0.8, 1.6, 2.4, or 3.2 mg/kg — in 35 SLE patients over a two-week treatment period. Treatment was administered subcutaneously (under-the-skin) on days 1 and 15.
Results showed itolizumab was generally safe and well-tolerated. The most frequently reported side effects were mild-to-moderate injection site reactions, none of which were serious. Levels of CD6 on T-cells’ surface also were reduced with treatment, according to Equillium.
Reductions in urine protein levels found
Exploratory efficacy analyses evaluated the treatment’s ability to lower the levels of proteins in the urine (proteinuria) — an indicator of kidney dysfunction. This is assessed by evaluating changes in the urine protein creatinine ratio (UPCR), with a higher UPCR reflecting greater proteinuria. Findings demonstrated that patients with proteinuria, but without a lupus nephritis diagnosis at enrollment, saw reductions in urine protein levels with treatment.
As such, the type B portion of the study, which aims to investigate the treatment’s safety, tolerability, and efficacy in about 20 people with active lupus nephritis, was expanded to include both newly diagnosed and refractory patients.
All participants are receiving itolizumab at a dose of 1.6 mg/kg every other week for 24 weeks with a follow-up lasting out to 36 weeks. Participants will also receive standard of care mycophenolate mofetil or mycophenolic acid (2–3 grams per day), and may receive short tapering rounds of systemic corticosteroids.
As of the interim analysis, 13 patients had been enrolled and dosed, with 11 people reaching at least 12 weeks of treatment and six who had already completed treatment.
At the study’s start, patients were highly proteinuric, with a mean UPCR of 5.8 grams of protein per gram of creatinine (g/g). Three out of six patients who finished treatment achieved at least a 50% reduction in UPCR, to a value less than 0.5–0.7 g/g, which investigators considered as a “complete response” to treatment. Two people achieved a partial response, a 50% UPCR reduction.
Overall, four of these six people achieved more than an 80% reduction in UPCR.
Among the 12 participants who had received at least one dose, eight have reached a more than 50% UPCR reduction, with an average reduction of 60%. Notably, the dose of steroids used for these patients was able to be reduced to a dose at or below 7.5 mg/day, in accordance with current recommendations.
“I’m impressed with these promising early and deep reductions in proteinuria, especially given the high nephrotic baseline levels,” said Kenneth Kalunian, MD, the trial’s principal investigator and a professor of clinical medicine at the University of California San Diego School of Medicine. “What is particularly striking are the higher overall response rates observed early in the treatment course that are not typically achieved with standard of care alone and that look competitive with data emerging from the recently approved drugs.”
The treatment was also generally safe and well-tolerated, with no itolizumab-related serious adverse events or treatment discontinuations. Equillium noted these data are preliminary and subject to change as additional findings become available.
“These interim results from the EQUALISE study are encouraging and provide the type of signal we’re looking for to advance a drug to larger controlled trials,” Kalunian said.