Itolizumab reduces urine protein levels in Phase 1B clinical trial

Therapy also appears able to lessen inflammatory activity of immune cells

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with the investigational injection therapy itolizumab significantly reduced urine protein levels, a marker of kidney dysfunction, in people with active lupus nephritis, a serious lupus complication marked by kidney damage and inflammation.

That’s according to top-line results from a Phase 1b trial called EQUALISE (NCT04128579) that were recently announced by the therapy’s developer, Equillium.

“Physicians want to rapidly and safely reduce the levels of proteinuria [urine protein levels] in patients with lupus nephritis, as this has been associated with improved long-term outcomes, so it is important that we saw both early and large reductions in proteinuria in this study,” Maple Fung, MD, chief medical officer at Equillium, said in a company press release.

Lupus is an autoimmune disease in which immune cells erroneously attack the body’s own healthy tissues. Itolizumab, which is given by subcutaneous (under-the-skin) injection, is designed to dampen the autoimmune attack that drives lupus, particularly lupus nephritis, by preventing an immune cell receptor called CD6 from interacting with a molecule called ALCAM.

The EQUALISE trial was conducted in two parts. In part A, people with systemic lupus erythematosus (SLE), the most common form of lupus, were given two injections of itolizumab, two weeks apart. In part B, 17 people with active lupus nephritis were treated with itolizumab, on top of standard treatments, with injections given every other week, for about six months. Participants then underwent a monitoring period of about another three months.

Interim results from part B, announced in 2022, indicated the therapy was well tolerated and capable of reducing proteinuria, as assessed by a standard measure called urine protein creatinine ratio (UPCR).

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16 patients finished full study

Equillium now announced top-line data from part B. Sixteen patients completed the full study and were analyzed for efficacy.

Prior to starting treatment, the mean UPCR was 4.9 grams of proteins per gram of creatinine (g/g), which indicates high levels of proteins in urine — the normal range for UPCR is around 0.7 g/g or less. By the end of the trial, the median UPCR had decreased by approximately 73%.

Six of the 16 evaluated participants had a complete response to treatment, with UPCR dropping by at least 50% and being at or below 0.7 g/g by the end of the study. Another seven participants had partial responses, with UPCR decreasing by at least 50% by the end of the study, even if it still wasn’t in the normal range.

According to Fung, these response rates are comparable to what was seen in clinical trials of Lupkynis (voclosporin), an approved treatment for lupus nephritis.

Patients in EQUALISE also notably reduced their dosage of corticosteroids while on treatment with itolizumab. Corticosteroids are powerful anti-inflammatory medicines that can be used to manage lupus, but can cause significant side effects, including weight gain and mood disorders, when used long-term.

“These itolizumab results occurred in the setting of patients tapering their systemic corticosteroids, maintaining stable kidney function … and increasing serum albumin [a marker of liver function] while on study,” Fung said.

Pharmacological data from EQUALISE also suggested itolizumab was capable of reducing the inflammatory activity of immune cells as designed. Safety data showed the experimental therapy was generally well tolerated. The most common side effects were low immune cell counts and swelling in the arms or legs, but none of the side effects related to itolizumab were judged to be severe.

Equilibrium has reported these findings to its partner, Ono Pharmaceutical. These Phase 1 findings are one of two large datasets that, once delivered, will trigger Ono to make a decision on whether or not to exercise an option to acquire rights to itolizumab, per a 2022 agreement between the companies. The second package of data, from a Phase 3 clinical trial in another immune disorder, is expected later this year, at which point Ono will make a final decision on whether or not to acquire the therapy.