Itolizumab Granted FDA Fast Track Designation as Potential Treatment for Lupus Nephritis

The U.S. Food and Drug Administration (FDA) has granted fast track designation to itolizumab as a potential therapy for lupus nephritis, a common and serious complication of systemic lupus erythematosus (SLE) that can lead to kidney failure.

This designation is given to compounds that show considerable potential in treating serious conditions for which available treatments fall short. It is meant to expedite clinical development, regulatory review, and entry into the market upon approval.

“While existing immunosuppressive therapies have improved five-year survival for lupus nephritis patients, more than half don’t have an adequate response to treatment, and many progress to end-stage [kidney] disease requiring dialysis or transplant,” Kenneth Kalunian, MD, the lead principal investigator of the ongoing EQUALISE Phase 1b study (NCT04128579) of itolizumab, said in a press release.

“There are no FDA approved therapies for lupus nephritis; however, the evaluation of itolizumab provides optimism that we may alleviate this significant unmet medical need for lupus nephritis patients,” he added.

Equillium’s itolizumab (EQ001) is a monoclonal antibody that selectively targets the CD6 receptor on the surface of immune T-cells. While T-cells are essential to fight infections and cancer, when abnormally activated, they can lead to inflammatory and autoimmune diseases, such as SLE.

The experimental treatment works by blocking the binding between CD6 and one of its ligands — ALCAM — which is found at higher levels in the urine of people with active lupus nephritis. By suppressing their interaction, itolizumab is thought to prevent immune responses mediated by T-cells, reduce kidney inflammation, and prevent further damage.

Preclinical data presented last month at the 2019 American College of Rheumatology and the Association of Rheumatology Professionals Annual Meeting supported the treatment’s potential.

In mouse models of SLE and lupus nephritis, itolizumab was found to ease kidney disease, while also decreasing the migration of T-cells to inflamed sites and increasing levels of interleukin (IL)-10, an anti-inflammatory molecule.

Data also showed that, compared to healthy controls, the number of CD6- and ALCAM-positive cells were increased in kidneys of people with lupus nephritis and were associated with disease activity. Urinary levels of ALCAM were significantly higher in active lupus nephritis — showing potential to be used to discriminate the active disease from inactive SLE or active SLE without lupus nephritis.

According to the company, itolizumab also suppressed T-cell development and proliferation, as well as inflammatory responses and molecules such as interferon-gamma, TNF-alpha, IL-6, and IL-17.

“Receiving Fast Track designation recognizes the promising therapeutic potential of itolizumab for the treatment for lupus nephritis, particularly given its ability to modulate both the activity and trafficking of effector T cells,” said Krishna Polu, MD, Equillium’s chief medical officer.

The EQUALISE study, initiated in September 2019, is evaluating itolizumab’s safety, pharmacokinetics (uptake, distribution, and elimination in the body), pharmacodynamics (the therapy’s effects on the body), and early effectiveness in up to 56 SLE patients with and without active lupus nephritis.

EQUALISE includes two groups of participants and treatment regimens. Type A consists of SLE patients to be treated with itolizumab for four weeks, while type B comprises people with active lupus nephritis randomly assigned to receive either itolizumab or a placebo for 12 weeks. Both itolizumab or a placebo will be given subcutaneously (under the skin) every two weeks.

Importantly, the EQUALISE trial is also measuring the levels of urinary biomarkers, including ALCAM and CD6, to assess their potential to predict disease progression and treatment response.

“[B]y monitoring levels of the CD6-ALCAM pathway in the urine in the EQUALISE trial we will be assessing the opportunity to take a personalized medicine approach to identify patients where the CD6-ALCAM pathway may be a dominant driver of the disease,” Polu said.