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Positive phase 2 data from 2 studies on the investigational monoclonal antibody felzartamab designed to deplete CD38+ plasma cells, demonstrated reduced pathogenic antibody levels in primary membranous nephropathy.
Human Immunology Biosciences (HI-Bio) announced positive data from two Phase 2 studies of felzartamab, an investigational monoclonal antibody designed to deplete CD38+ plasma cells in patients with primary membranous nephropathy (PMN).1
PMN is a rare, immune-mediated kidney disease with a high burden, affecting more than 36,000 patients in the US, and has no therapies approved for treatment by the US Food and Drug Administration (FDA).
The current standard of care comprises off-label use of immunosuppressive agents, but nearly one-third of patients progress to end-stage renal disease (ESRD), and half continue to have nephrotic syndrome, a condition of high proteinuria.
“PMN is one of the most common causes of nephrotic syndrome, resulting in severe proteinuria, edema, fatigue, progression to ESRD and increased risk of thromboembolism and infection,” Brad Rovin, MD, Director of the Division of Nephrology at Ohio State University stated. “We need to advance clinical immunology to a point where diseases like PMN can be turned into manageable conditions with deep and durable remissions."
The investigation enrolled 55 patients with newly diagnosed or relapsed/refractory PMN across 2 clinical studies, M-PLACE, and NewPLACE, with a median anti-PLA2R (aPLA2R) serum titer of 197 RU/mL. aPLA2R is suspected to be the driver of up to 80% of PMN cases, according to the announcement.
Results indicated a dose-dependent reduction in pathogenic antibody levels in patients treated with felzartamab. The most durable reductions were observed in the 9-dose arm, compared with the 2- and 5-dose regimens.
Early and substantial reductions in titers were seen in many patients as early as one week >50% reduction), with prominent responses in most patients at the conclusion of 6 treatment months.
Investigators saw robust reduction of autoantibody levels measured regardless of initial aPLA2R titer, including in patients with high baseline titers who typically have increased risk of disease severity and progression as well as lower expected response to standard therapies.
Moreover, improvements in proteinuria and serum albumin levels were apparent with the administration of felzartamab, indicating potential renal recovery. Proteinuria remissions included patients previously found to be refractory to anti-CD20 therapies sucha as rituximab and cyclophosphamide.
Across both studies, felzartamab was generally well-tolerated, with the majority of treatment-emergent adverse events (TEAEs) being mild-moderate and consistent with the known mechanism of action of felzartamab in the PMN population.
The study exhibited the most common TEAE was infusion-related reactions on the first infusion that were mostly mild to moderate in intensity. Among all patients, 4 of 55 (7.3%) had a TEAE leading to treatment discontinuation that was deemed related to the intervention.
HI-Bio stated its intention to advance felzartamab into late-stage development in PMN and other autoantibody-driven immune-mediated diseases, as it has shown promising results in depleting pathogenic antibody levels in PMN. Felzartamab has the potential to turn PMN into a manageable condition with deep and durable remissions and has the potential to become the first approved therapy for this rare disease.
“These results, the tolerability profile observed, and the fact that PMN is a high burden disease with no approved therapies all support our intention to advance felzartamab into late-stage development and discuss the path forward with regulators," Travis Murdoch, MD, CEO, HI-Bio, stated. "We are focused on developing felzartamab in PMN and other autoantibody driven IMDs where patients have serious unmet needs.”