Biogen has reported encouraging phase 2 results with its anti-CD38 antibody felzartamab in IgA nephropathy (IgAN), a rare autoimmune kidney disease that represents a leading cause of kidney failure. The data, presented at Kidney Week 2024 in San Diego, showed substantial reductions in proteinuria and stabilized kidney function in the 54-subject IGNAZ study.
Clinical Trial Results
In the IGNAZ study, patients received a nine-dose regimen of felzartamab over a six-month treatment period, with follow-up extending 18 months after the last dose. The results demonstrated a 50% reduction in proteinuria levels after two years of follow-up, while estimated glomerular filtration rate (eGFR) levels were maintained over that period.
The positive outcomes represent an early validation of Biogen's recent $1.8 billion acquisition of Human Immunology Biosciences (HI-Bio), which brought felzartamab into the company's pipeline as part of its strategic pivot toward immunology programs to complement its neuroscience focus.
Mechanism of Action and Disease Background
According to the American Society of Nephrology (ASN), IgAN is an autoimmune kidney disease driven by immune cells that express CD38 protein on their surface. CD38-expressing cells contribute to disease progression through the secretion of antibodies that form immune complexes, which subsequently deposit in the kidneys and cause inflammation and loss of kidney function.
Felzartamab's therapeutic approach involves depleting these antibody-secreting cells, thereby reducing the cellular drivers of disease. This mechanism could potentially provide durable clinical benefit with intermittent dosing, "potentially lowering patient burden and offering improved tolerability," according to Biogen.
Market Context and Unmet Need
IgAN affects approximately 130,000 people in the United States and another 115,000 in Europe. The disease has historically had limited treatment options, with the first FDA-approved therapy, Calliditas Therapeutics' corticosteroid-based Tarpeyo (budesonide), gaining approval in 2021. This was followed by Travere Therapeutics' endothelin antagonist Filspari (sparsentan) last year and Novartis' oral complement factor B inhibitor Fabhalta (iptacopan) just weeks ago.
Despite these recent approvals, significant unmet medical need remains. "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," commented Uptal Patel, head of development of HI-Bio at Biogen.
Broader Development Program
Beyond IgAN, felzartamab is being evaluated across multiple kidney-related indications. The drug is currently in mid-stage clinical trials for primary membranous nephropathy (PMN) and antibody-mediated transplant rejection, and is in phase 1 development for lupus nephritis.
Looking ahead, Biogen has initiated three pivotal phase 3 studies for felzartamab across multiple kidney indications, with the first data readout anticipated in 2027 from the TRANSCEND study evaluating the drug in adult kidney recipients diagnosed with late antibody-mediated rejection.
Future Outlook
The competitive landscape for IgAN continues to evolve, with additional potential therapies in development including APRIL-targeting antibodies from Novartis and Otsuka. However, felzartamab's unique mechanism of targeting CD38-expressing cells positions it as a potentially differentiated therapeutic approach.
Based on the encouraging phase 2 results, Biogen is now planning to advance felzartamab into a phase 3 program for IgAN, representing a significant milestone in the development of this investigational anti-CD38 monoclonal antibody platform.
