Biogen Launches Global Phase 3 PROMINENT Trial Evaluating Felzartamab in Primary Membranous Nephropathy
Biogen Inc. (Nasdaq: BIIB) has announced the initiation of dosing in its global Phase 3 clinical trial, known as PROMINENT, to assess the safety and efficacy of its investigational anti-CD38 antibody, felzartamab, in adults with primary membranous nephropathy (PMN). This randomized, open-label study will compare felzartamab with tacrolimus, a commonly used immunosuppressant, in a cohort of approximately 180 patients worldwide. The trial is expected to complete in 2029.
Primary membranous nephropathy is a rare and serious autoimmune kidney disease characterized by the formation of autoantibodies that damage the glomerular basement membrane, often resulting in nephrotic syndrome—a condition marked by high levels of protein in the urine, severe swelling, and a significant risk of progression to kidney failure. Despite its impact, there are currently no FDA-approved therapies for PMN, and treatment options are limited to non-specific and often toxic agents such as chemotherapy or general immunosuppressants.
A Precision-Targeted Approach to an Unmet Need
Felzartamab is a monoclonal antibody that targets CD38, a protein found on plasma cells, which are responsible for producing the pathogenic autoantibodies in many immune-mediated diseases. Notably, in PMN, up to 80% of patients generate anti-phospholipase A2 receptor (aPLA2R) autoantibodies via CD38+ plasma cells. By selectively depleting these cells, felzartamab offers a promising, mechanism-driven approach to potentially halting disease progression.
“Launching the PROMINENT trial represents a meaningful step forward for people living with PMN, a disease that carries a high burden and limited treatment choices,” said Travis Murdoch, Head of the Biogen West Coast Hub. “This is the third Phase 3 study for felzartamab that Biogen has initiated this year, highlighting our deep commitment to expanding treatment possibilities for kidney diseases.”
Trial Design and Objectives
The PROMINENT trial (NCT06962800) is a 104-week, global multicenter study involving adults with moderate- to high-risk PMN, including those newly diagnosed or experiencing disease relapse. Participants will be randomized to receive either felzartamab or tacrolimus, and the primary endpoint is the percentage of participants achieving complete remission of proteinuria at week 104.
Secondary endpoints will include:
- Changes in serum aPLA2R antibody levels,
- Renal function metrics, and
- Patient-reported outcomes related to quality of life.
Importantly, the study will include both aPLA2R-positive and -negative patients and stratify enrollment accordingly, allowing for a broader understanding of felzartamab’s efficacy across PMN subtypes.
Clinical Community Welcomes Innovation
Dr. Mohamed El-Shahawy, Clinical Professor at the Keck School of Medicine at the University of Southern California and one of the trial’s principal investigators, emphasized the significance of the trial: “PMN remains a largely unaddressed condition in nephrology. Felzartamab’s mechanism of depleting the very plasma cells responsible for disease-driving antibodies gives us hope for a meaningful therapeutic advance. I’m grateful that Biogen is prioritizing this rare disease and advancing research that could ultimately change clinical practice.”
Supporting Evidence from Phase 2 Trials
Felzartamab’s development is underpinned by promising results from two prior Phase 2 studies, M-PLACE (n=31) and NewPLACE (n=24), which focused on patients with aPLA2R-positive PMN. In the M-PLACE trial, participants showed a median 45% reduction in aPLA2R titers within one week of treatment, with over half showing significant responses by six months. These biomarker improvements were accompanied by favorable changes in proteinuria and serum albumin levels.
Safety data from both trials showed that most treatment-emergent adverse events (TEAEs) were mild to moderate in intensity, with infusion-related reactions being the most commonly observed side effect—primarily during the first infusion.
A Broad Kidney Disease Pipeline
Beyond PMN, felzartamab is currently being investigated in two additional Phase 3 trials launched this year by Biogen:
- TRANSCEND (NCT06685757), targeting late antibody-mediated rejection in kidney transplant recipients.
- PREVAIL (NCT06935357), evaluating felzartamab in patients with IgA nephropathy, another progressive autoimmune kidney disease.
About Felzartamab
Felzartamab is a fully human monoclonal antibody against CD38, originally developed by MorphoSys AG (now MorphoSys GmbH, a Novartis company). The rights to felzartamab were licensed to Human Immunology Biosciences (HI-Bio), which Biogen acquired in July 2024. Biogen now holds global development and commercialization rights for felzartamab, excluding China (including Macau, Hong Kong, and Taiwan).
Felzartamab is currently an investigational product and has not yet received approval from any regulatory authority.
About Primary Membranous Nephropathy (PMN)
PMN affects approximately 36,000 patients in the United States and is a leading cause of nephrotic syndrome in adults. The disease arises from an autoimmune attack on the kidney’s filtration units, often leading to massive protein loss, swelling, fatigue, and risk of life-threatening infections. Despite the severity of PMN, nearly one-third of patients fail to achieve remission with current treatment strategies. This underscores the urgent need for targeted and durable therapeutic options.
