HI-Bio Receives FDA Orphan Drug Designation for Felzartamab for the Treatment of Membranous Nephropathy
SOUTH SAN FRANCISCO, Calif., – May 25, 2023 – Human Immunology Biosciences (HI-Bio™), a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for felzartamab, the company’s investigational agent that is in development for the treatment of primary membranous nephropathy (PMN). Felzartamab is an investigational monoclonal antibody designed to deplete CD38+ plasma cells, which are believed to drive PMN through the production of pathogenic autoantibodies. The company intends to advance felzartamab into late-stage studies.
“The FDA’s orphan drug designation for felzartamab is an acknowledgment of the critical and ongoing unmet need in PMN and the potential for felzartamab to be an important new therapeutic option to improve the lives of patients with PMN who currently have very limited treatment options,” said Uptal Patel, M.D., Chief Medical Officer at HI-Bio. “We are excited to advance our clinical development program to make progress on our goal of transforming PMN into a well-managed condition.”
PMN is a rare IMD affecting the kidneys, impacting more than 36,000 people 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 therapies like cyclophosphamide, and CD20-targeted B-cell depleting agents. Even with these strategies, half of patients with PMN continue to have nephrotic syndrome and nearly one third progress to kidney failure.
As recently announced, positive data was achieved for felzartamab in patients with PMN across two Phase 2 studies. Beyond PMN, felzartamab is currently in development for IgA Nephropathy and Antibody Mediated Rejection of kidney transplants. The company intends to explore developing felzartamab in additional IMDs where patients have serious unmet needs.
The FDA’s Orphan Drug Designation program is designed to advance the development of drugs and biologics intended to treat a rare disease or condition that affects fewer than 200,000 people in the United States. Orphan drug designation qualifies HI-Bio for certain development incentives, including tax credits for qualified clinical trials, exemption of FDA application fees and up to seven-year market exclusivity upon regulatory approval.
About Primary Membranous Nephropathy (PMN)
PMN is a rare autoantibody-mediated autoimmune kidney disease and a leading cause of nephrotic syndrome (NS) in adults worldwide. Disease onset and diagnosis typically occurs between 40 and 50 years of age, with 80% of patients presenting with Nephrotic Syndrome (i.e., edema, >3.5 g/day proteinuria, hypoalbuminemia). PMN is characterized by a thickening of the glomerular basement membrane (GBM) due to the formation and deposition of immune complexes in this space between podocytes and the glomerular endothelium of the kidney.
Approximately 80% of PMN cases arise due to autoantibodies that recognize the phospholipase A2 receptor (PLA2R) antigen expressed on podocytes. Anti-PLA2R is both a diagnostic and prognostic biomarker, and total aPLA2R antibody level has been shown to be a biomarker for prognosis of outcome in patients with PMN. Other autoantibodies have been identified in patients with PMN including anti-THSD7A, NELL-1 and Sema3B, further supporting the role of antibody-secreting plasma cells in the pathophysiology of PMN. CD38+ long lived plasma cells and plasmablasts are a main source of autoantibodies.
There are no approved therapies for PMN. The current standard of care comprises off-label use of supportive care measures (e.g., angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and diuretics), conventional immunosuppressive treatments (ISTs) (e.g. cyclophosphamide combined with steroids and calcineurin inhibitors) or B-cell depleting agents (e.g. anti-CD20 antibodies). However, these treatments are not effective in all patients, with a significant proportion of patients not achieving remission or relapsing. In addition, conventional immunosuppressive treatments are associated with a high risk of toxicity.
About Felzartamab
Felzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. In PMN, CD38+long-lived plasma cells drive pathogenic antibody production, contributing to functional damage to the glomeruli in the kidney. By targeting CD38, felzartamab has the potential to deplete CD38+ plasma cells while leaving other functionally important plasma cells intact, which may ultimately improve clinical outcomes in a broad range of autoantibody driven diseases.
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.
Felzartamab is an investigational drug that has not yet been approved by any regulatory authorities.