Atacicept Demonstrates Ability to Reduce Serum Gd-IgA1 in IgAN Patients

Jonathan Barratt, PhD

New data show atacicept can reduce both circulatory Gd-IgA1 and anti-GdlgA1, as well as immune complex levels in patients with immunoglobulin A nephropathy (IgAN).

A team, led by Jonathan Barratt, University of Leicester, investigated whether atacicept can also reduce immune complex levels in patients with IgAN.

The Disease

IgAN is an autoimmune disease that could have a multi-hit mechanisms in the inflammatory pathogenic process. It is known that elevated serum Gd-IgA1 plays a key role in IgAN pathogenesis as the first hit. The second hit is likely antibodies developing against Gd-IgA1 (anti-Gd IgA1) leading to formation of immune complexes, which is the third hit.

The circulating immune complexes can then deposit in the kidney and cause a fourth hit injury.

Testing the Novel Treatment

In the randomized, placebo-controlled, Ph2a JANUS trial, the investigators found that atacicept was the first therapeutic to decrease both circulatory Gd-IgA1 and anti-Gd-lgA1.

In the study, the investigators evaluated patients in the JANUS study for serum IgA-IgG immune complex levels by ELISA at baseline, weeks 4, 12, 24, 48, and 72.

In this trial, atacicept administered subcutaneously once weekly resulted in a substantial reduction in serum Gd-IgA1 in a dose dependent manner that was durable through 72 weeks. The largest overall effect was seen in the atacicept 75 mg group, where after 24 weeks all participants had reductions in serum Gd-IgA1 to the lowest quartiles. This is associated with the most favorable renal survival outcomes.

The investigators also found a decrease in serum anti-Gd-IgA1 levels in both the atacicept 25 mg and atacicept 75 mg arms over time.

The results show there were serum IgA-IgG immune complex levels decreases in both patients treated with atacicept 25 mg ab atacicept 75 mg over time.

At week 24, the mean percent change from baseline was 17% decreased for the atacicept 25 mg group, a 21% decrease for the atacicept 75 mg group, and a 3% decrease for placebo.

For the 72 week results, there was a 29% decrease in the atacicept 25 mg group, a 26% decrease in the atacicept 75 mg group, and only a 13% decrease for the placebo cohort observed.

Overall, atacicept is the first ever therapeutic to show a reduction in serum Gd-IgA1, anti-Gd-IgA1, and immune complex levels in patients with IgAN.

“Atacicept’s ability to mitigate all of the first three hits of the multi-hit hypothesis illustrates its potential to modify the disease,” the authors wrote. “The ongoing Ph2b ORIGIN trial evaluating up to atacicept 150 mg in IgAN pts, will help determine how reduction of these multiple hits translate to renal function.”

The data was presented during the 2022 American Society of Nephrology (ASN) Annual Meeting in Orlando.

The study, “Atacicept Reduces Serum Immune Complex Levels in Patients With IgA Nephropathy (IgAN),” was published online by ASN.