Investigators have initiated dosing in the Phase III PROMINENT trial (NCT0696280) evaluating the investigational anti-CD38 antibody felzartamab (Biogen) in the treatment of primary membranous nephropathy (PMN).

Biogen Launches Phase 3 PROMINENT Trial of Felzartamab for Primary Membranous Nephropathy

There are currently no FDA-approved treatments for PMN, a rare and serious autoimmune kidney disease, emphasizing the significance of the trial program for this patient population.^1,2

“We are encouraged by the opportunity to advance a Phase III study for [PMN], a condition that carries a significant risk of kidney failure,” said Travis Murdoch, head of the Biogen West Coast Hub, in a press release. “This is the third Phase III trial of felzartamab launched by Biogen this year, underscoring our ongoing commitment to developing potential novel treatment options for patients living with kidney disease.”¹

Felzartamab Targets CD38+ Cells in a High-Need PMN Population

Felzartamab, a fully human anti-CD38 monoclonal antibody, has received Breakthrough Therapy Designation and Orphan Drug Designation (ODD) by the FDA for the treatment of PMN. It was also granted ODD for antibody-mediated rejection in patients who received a kidney transplant. Biogen gained rights to the drug when it acquired Human Immunology Biosciences in May 2024.³

Research has shown felzartamab selectively depletes CD38+ cells and plasma cells, which are the source of autoantibodies that attack the body’s own tissues in various immune-mediated diseases. Notably, investigators estimate that approximately 80% of patients with PMN carry autoantibodies against PLA2R that are produced by CD38-expressing plasma cells.¹

Findings from a Phase II trial (NCT05021484) published by The New England Journal of Medicine found that felzartamab demonstrated a potential therapeutic benefit and an acceptable safety and adverse event (AE) profile in patients with antibody-mediated rejection occurring at least 180 days following kidney transplantation.^4,5

In that trial, eight of 11 patients administered felzartamab reported mild or moderate infusion reactions. Serious AEs were observed in one patient in the felzartamab cohort and four of 10 patients in the placebo cohort, with graft loss occurring in one patient in the placebo cohort. After 24 weeks, morphologic antibody-mediated rejection resolved more frequently in nine of 11 patients in the felzartamab cohort compared with two of 10 patients in the placebo cohort, which translates to a difference of 62 percentage points (95% confidence interval [CI], 19 to 100) and a risk ratio of 0.23 (95% confidence interval [CI], 0.06 to 0.83).

PROMINENT Trial's Primary Endpoint to Evaluate for Complete Remission

The 104-week, randomized, open-label, global, multicenter Phase III PROMINENT trial will compare the efficacy and safety of felzartamab vs. tacrolimus in producing complete remission of proteinuria in patients with moderate-to-high-risk PMN, including both newly diagnosed and relapsed participants. Investigators anticipate enrolling approximately 180 patients with PMN and project readout in 2029.

The trial’s primary endpoint is percentage of patients experiencing complete remissions at week 104. Investigators will analyze anti-PLA2R autoantibody positive and negative patients, who will be stratified based on PLA2R levels. The trial’s key secondary endpoints include efficacy of felzartamab on serum anti-phospholipase A2 receptor antibodies and patient-reported outcomes.

Felzartamab’s Broader Clinical Program Reflects Biogen’s Kidney Disease Strategy

Two other Phase III trials evaluating felzartamab are planned for this year, which include the TRANSCEND (NCT06685757)⁶ trial analyzing the drug’s efficacy treating late antibody-mediated rejection in adults who underwent kidney transplantation and the PREVAIL trial (NCT06935357)⁷ in patients with IgA nephropathy.

“Primary membranous nephropathy remains an unaddressed area of nephrology, for which there are no approved treatments. Felzartamab’s mechanism of action designed to deplete the cells that produce the pathogenic antibodies is exciting news for patients that are waiting for potential meaningful new treatment options,” PROMINENT trial principal investigator Mohamed El-Shahawy, MD, MPH, MHA, director of the Academic Research Institute in Los Angeles, clinical professor of Medicine at Keck-University of Southern California School of Medicine, said in the release. “I’m grateful that Biogen is advancing research in this rare kidney disease and am eager to see the continued progress in the study’s enrollment.”¹

References

1. Biogen Initiates Phase 3 Study of Felzartamab for the Treatment of Primary Membranous Nephropathy. News release. Biogen. June 30, 2025. Accessed June 30, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-initiates-phase-3-study-felzartamab-treatment-primary

2. A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Primary Membranous Nephropathy (PMN) (PROMINENT). ClinicalTrials.gov. Updated June 5, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT06962800

3. Biogen Bolsters Late-Stage Pipeline, Expands Immunology Portfolio with Agreement to Acquire Human Immunology Biosciences. News release. Biogen. May 22, 2024. Accessed June 30, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-bolsters-late-stage-pipeline-expands-immunology-portfolio

4. Mayer K, et al. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med 2024;391:122-132 DOI: 10.1056/NEJMoa2400763. Vol. 391 No. 2.

5. Felzartamab in Late Antibody-Mediated Rejection. ClinicalTrials.gov. April 18, 2024. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05021484

6. A Trial of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR) (TRANSCEND). ClinicalTrials.gov. Updated June 17, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT06685757

7. A Study to Learn About the Effects of Felzartamab Infusions on Adults With Immunoglobulin A Nephropathy (IgAN) (PREVAIL). ClinicalTrials.gov. Updated June 17, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT06935357