Felzartamab Slows IgAN Decline in New Phase 2 Data

Jonathan Barratt, MBChB, PhD

Credit: George Clinical

Felzartamab was well-tolerated, led to sustained proteinuria reductions, and reduced estimated glomerular filtration rate (eGFR) decline in patients with IgA nephropathy (IgAN) compared to placebo.¹

These findings were complete 24-month data,from the randomized, double-blind, placebo-controlled phase 2a IGNAZ study, were presented at The American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California, held October 23-26, by Jonathan Barratt, MBChB, PhD, Mayer Professor of Renal Medicine, University of Leicester, Leicester, United Kingdom.

"The complete results of the IGNAZ Study reaffirm our interim findings, showing a reduction in proteinuria, stabilization of kidney function, and sustained treatment effect more than 18 months after the last dose of felzartamab,” Barratt said in a statement.² “This is promising news for patients and supports the potential of felzartamab to be a meaningful treatment option for people living with IgA nephropathy, a leading cause of chronic kidney disease.”

Felzartamab is a monoclonal antibody that targets CD38 on plasma cells, which is suspected as the source of pathogenic Gd-IgA1 and autoantibodies in IgAn. In the IGNAZ study, Barratt and colleagues enrolled patients aged between 18 and 80 years with biopsy-confirmed IgAN, proteinuria levels of at least 1.0 g/day (at least 0.5 g/days in Japanese patients), and eGFR levels of at least 30 mL/min per 1.73m2. Participants were using renin-angiotensin inhibitors for at least 3 months at baseline and were randomized to placebo (n = 12), 2 doses of felzartamab in 15 days (n = 12), 5 doses of felzartamab in 2 months (n = 11), or 9 doses felzartamab in 5 months (n = 13). In the second part of the study, 6 Japanese patients received open-label 9 doses in 5 months.¹

The participants were mostly men (64%), with a mean age of 41.6 years, urine protein creatinine ratio (UPCR) of 1.7 g/g, and eGFR levels of 74.6 mL/min per 1.73m2. Forty of 48 participants completed treatment in part 1.¹

The investigators found that participants treated with felzartamab experienced rapid, clinically meaningful reductions in UPCR compared with placebo, with participants that received 9 doses in 5 months experiencing the most pronounced effect. Participants treated with felzartamab had mean eGFR decline less than those treated with placebo and had rapid and durable IgA reductions which lasted 19 months after the last dose, with IgG recovering by 6-9 months.¹

Findings were similar in the 6 patients in part 2 of the study. Felzartamab was generally well-tolerated, with dose-independent grade 1 or 2 treatment-emergent adverse events (AEs). The most common treatment-related AE was infusion related reactions, mostly during the first dose. One infusion related reaction was considered a serious AE and 5 participants discontinued felzartamab due to these reactions. There were also a number of nonserious, grade ½ infections across felzartamab arms.¹

“We are encouraged by the overall results of the IGNAZ study, especially given the significant unmet medical need for additional treatments to address high-risk IgA nephropathy,” Uptal Patel, MD, Head of Development, HI-Bio at Biogen added.² “We are grateful to all the participants, investigators and study staff who contributed to this study, whose findings will help us continue to evaluate felzartamab’s role in preserving kidney function as we plan for Phase 3.”

REFERENCES
1. Barratt J, Floege J, Lafayette RA, et al. Felzartamab for IgA Nephropathy: Final Results of the IGNAZ Study. Presented at: ASN Kidney Week 2024, October 23-26; San Diego, California

2. Biogen Presents Positive Results from Phase 2 IGNAZ Study of Felzartamab in IgA Nephropathy at American Society of Nephrology (ASN) Kidney Week 2024. News release. Biogen. October 26, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-presents-positive-results-phase-2-ignaz-study-felzartamab