Benefits of investigational IgA nephropathy drug persist for 72 weeks

Patients with IgA nephropathy (IgAN) who have been treated with atacicept continue to show improvement in disease status through 72 weeks, with consistent reductions in the key indicators of IgAN and the kidney function remaining stable, according to the open-label extension phase of the phase IIb ORIGIN study.

The 72-week interim data with atacicept are consistent with a disease-modifying IgAN profile, reported lead study investigator Dr Richard Lafayette, director of the Stanford Glomerular Disease Center at Stanford University Medical Center in Stanford, California, US.

In the group of patients who received atacicept continuously, galactose-deficient IgA1 (Gd-IgA1) levels dropped by a further 3 percent, reaching –62 percent at week 72 compared with –59 percent at week 36 at the end of the double-blind treatment. Persistent reductions were also observed in the proportion of patients with hematuria (from –67 percent to –81 percent) and in urine protein:creatinine ratio (UPCR; from –34 percent to –45 percent). [ERA 2024, abstract 812]

Patients who switched from placebo to atacicept at week 36 saw comparable reductions in outcome measures as those who received the drug from the beginning (Gd-IgA1 levels: from –7 percent at week 36 to –59 percent at week 72; hematuria rate: from –5 percent to –59 percent; UPCR: from 3 percent to –47 percent).

As for kidney function, Lafayette noted that eGFR remained stable among patients who initially received atacicept but was only stabilized following the switch among those who initially received placebo.

“The demonstration of stable eGFR well beyond a year in participants receiving atacicept represents an important potential advancement for IgAN patients and has potential implications for the future treatment paradigm in this disease,” the investigator stated.

“It is also exciting [to see] that switching to atacicept halted the eGFR decline seen in participants initially treated with placebo, with similar reductions in Gd-IgA1, hematuria, and UPCR as shown in the active cohort in the first 36 weeks,” he added.

Looking at safety, the data accumulated during the open-label extension align with the observations from the double-blind treatment phase of ORIGIN clinical trial, Lafayette noted. “Atacicept was generally well tolerated.”

From baseline to week 72, the rate of treatment-emergent adverse events (TEAEs) with atacicept 150 mg was 79 percent. Infections and infestations occurred in 45 percent of patients, and study drug-related TEAEs were reported in 67 percent. Two patients had serious TEAEs, and one discontinued treatment due to TEAEs. None of the patients died.

The 72-week results “provide evidence of possible long-term, comprehensive IgAN disease modification and additional confidence in the ongoing phase III ORIGIN 3 study,” Lafayette said.

ORIGIN included 116 patients (mean age 39 years, 59 percent male, 44 percent Asian) with biopsy-proven IgAN, 24-h urine protein >0.75 g/day or UPCR >0.75 g/g, and eGFR ≥30 mL/min/1.73 m². These patients were randomly assigned to treatment with atacicept at 150 (n=33), 75 (n=33), or 25 mg (n=16) or placebo (n=34), self-administered by subcutaneous injection.

A total of 111 patients completed the 36-week treatment and entered the open-label extension, of which 80 were from the atacicept arms and 31 were from the placebo arm. These patients were given atacicept at 150 mg for up to 60 additional weeks.