HI-Bio Reports Positive Phase 2 Data on Felzartamab for Treatment of Primary Membranous Nephropathy

Rare Daily Staff

Human Immunology Biosciences, a clinical-stage company developing targeted therapies for patients with severe immune-mediated diseases, reported positive data from two phase 2 studies of felzartamab for the treatment of primary membranous nephropathy, a rare, immune-mediated kidney disease.

Felzartamab showed dose-dependent reduction in pathogenic antibody levels across the two clinical studies, M-PLACE and NewPLACE, and proteinuria remission was observed across patient groups, including those starting with high aPLA2R titers or refractory to prior immunosuppressive therapies

Primary membranous nephropathy (PMN) is a rare, high burden disease that impacts more than 36,000 patients in the United States. There are currently no approved therapies for PMN. Standard of care comprises off-label use of a variety of agents, including immunosuppressive cyclophosphamide and CD20-targeted B-cell depleting agents. Even with these strategies, half of PMN patients continue to have nephrotic syndrome and nearly one third progress to end-stage renal disease (ESRD). aPLA2R autoantibodies are thought to be drivers of disease in as much as 80 percent of PMN cases. Persistent elevated aPLA2R levels are associated with worse response to immunosuppressive therapy, longer time to remission and high risk of progression to kidney failure.

Felzartamab is an investigational monoclonal antibody designed to deplete CD38+ plasma cells, which are believed to drive primary membranous nephropathy (PMN) through the production of anti-PLA2R (aPLA2R) autoantibodies. The company intends to advance felzartamab into late-stage studies in PMN and other autoantibody-driven immune-mediated diseases.

M-PLACE was a phase 1b/2a proof-of-concept, open-label, multinational study to assess safety and efficacy in adults with aPLA2R-positive PMN using a five-month (nine-dose) course. The study enrolled 31 patients who were newly diagnosed and relapsed or refractory to immunotherapies.

NewPLACE is a two-arm, multi-center, open-label, parallel-group phase 2 trial that enrolled 24 patients to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of alternative two- and five-dose courses, over two weeks and two months respectively, and retreatment of felzartamab in patients with aPLA2R-positive PMN indicated for immunosuppressive therapy. The studied dose level across both studies and all arms was consistent with the target dose for felzartamab at 16 mg/kg.

The most durable reductions in aPLA2R levels were observed in the nine-dose arm as studied in M-PLACE, as compared to the two- and five-dose regimens studied in NewPLACE. Together, these studies enrolled a population of patients with the highest median aPLA2R serum titers as measured with an FDA-cleared immunoassay in a therapeutic clinical study to date.

In the final analysis of M-PLACE, early and substantial reductions in aPLA2R titers were observed in most patients as early as one week (median reduction of 45 percent), with deep responses (>50 percent reduction) in most patients at six months at end-of-treatment. A deepening or maintenance of response in the majority of responders after end-of-treatment through month 12 was observed. Robust reduction of autoantibody levels was measured regardless of initial aPLA2R titer including in patients with high baseline titers, who typically have increased risk of disease severity and progression, and lower expected response to standard of care therapies.

In M-PLACE, improvements in proteinuria and serum albumin levels were observed with administration of felzartamab, highlighting potential renal recovery. Proteinuria remissions included patients previously found to be refractory to anti-CD20 therapies (e.g., rituximab) and cyclophosphamide.

Across both studies, felzartamab was found to be generally well tolerated. The majority of treatment emergent adverse events (TEAEs) reported were mild to moderate and consistent with the known mechanism of action of felzartamab in the PMN population. The most common TEAE was infusion-related reactions on the first infusion that were mostly mild to moderate in intensity. In all, four of 55 patients (7.3 percent) had a TEAE leading to treatment discontinuation that was deemed related to study drug. Further, as published in Kidney International Reports in 2022, humoral response to immunization with SARS-CoV-2 vaccines was preserved with felzartamab use.

The company intends to present further data on the M-PLACE and NewPLACE studies at an upcoming medical meeting.

“These data are very encouraging, demonstrating robust responses with proteinuria remissions in high-risk treatment naïve and refractory patients,” said Travis Murdoch, CEO of HI-Bio. “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. We are focused on developing felzartamab in PMN and other autoantibody driven IMDs where patients have serious unmet needs.”

HI-Bio is currently evaluating the safety and efficacy of investigational felzartamab for patients with aPLA2R antibody-positive membranous nephropathy (in the M-PLACE and NewPLACE trials) and Immunoglobulin A Nephropathy (IGNAZ trial). Felzartamab is also being evaluated in investigator-initiated studies for PMN in patients who have had inadequate response to anti-CD20 and for antibody mediated rejection (AMR) of renal allograft transplants. HI-Bio in-licensed felzartamab from MorphoSys in June 2022, and holds executive worldwide rights for felzartamab with the exception of Greater China.

In 2017, MorphoSys entered into an exclusive regional licensing agreement with I-Mab Biopharma to develop and commercialize felzartamab in Greater China which encompasses Mainland China, Hong Kong, Macau, and Taiwan. I-Mab is evaluating felzartamab in relapsed/refractory multiple myeloma.

Photo: Travis Murdoch, CEO of HI-Bio