82% (n=9/11) of patients on felzartamab
experienced resolution of antibody-mediated rejection
per Banff criteria on biopsy at 24 weeks versus 20% (n=2/10) who
received placebo, and patients treated with felzartamab showed
reductions in disease-linked biomarkers and stabilization of
eGFR
63% (n=7/11) of felzartamab-treated patients
achieved microvascular inflammation (MVI) score of 0 and 100%
(n=11/11) of felzartamab treated patients had an improvement in MVI
score
Results published in New England Journal of
Medicine and presented at 61st European Renal
Association (ERA) Congress
Results support advancement of felzartamab
into late-stage development as a novel therapeutic approach in
antibody-mediated rejection
SOUTH
SAN FRANCISCO, Calif., May 25, 2024
/PRNewswire/ -- Human Immunology Biosciences (HI-Bio™), a
clinical-stage biotechnology company developing targeted therapies
for patients with severe immune-mediated diseases (IMDs), today
announced positive results from a Phase 2 investigator-sponsored
clinical trial of felzartamab for late antibody-mediated rejection
(AMR) in kidney transplant recipients.
Felzartamab is an investigational monoclonal antibody designed
to specifically target and deplete CD38+ cells, which can include
plasmablasts, plasma cells and natural killer (NK) cells, which are
believed to drive AMR and other IMDs. This double-blind,
placebo-controlled Phase 2 study was designed to assess the safety
and tolerability of felzartamab in adults with late AMR occurring
at least 180 days after kidney transplantation. Patients were
randomized 1:1 to receive nine infusions of felzartamab (16 mg/kg)
or placebo over 20 weeks, followed by an observation period of 32
weeks. Biopsies were taken at baseline, 24 weeks and 52 weeks. The
study enrolled 22 patients.
Felzartamab had acceptable safety and side-effect profiles in
patients with late AMR. Most adverse events were mild or moderate
in severity. Mild or moderate infusion reactions, typically on the
first infusion, occurred in patients in the felzartamab group
(n=8). There were no treatment-related discontinuations.
Key secondary endpoints demonstrated potential for felzartamab
to be the first effective therapeutic for late AMR, resolving
disease according to the Banff Classification. The classification
is the international standard for characterizing kidney
transplant-related disease, including late rejection.
In the treatment arm, 82% (n=9/11) of patients experienced
resolution of AMR at week 24, compared to 20% (n=2/10) who received
placebo. One placebo patient had a graft loss at week 14, likely
due to persistent, chronic active AMR. The median microvascular
inflammation (MVI) score was lower in the felzartamab group than in
the placebo group (0 vs. 2.5) at week 24 with 64% (n=7/11) of
felzartamab-treated subjects achieving an MVI score of 0. Of those
who experienced resolution at 24 weeks, 67% (n=6/9) maintained
resolution at 52 weeks, with no drug being administered during the
observation period. Additionally, deep reduction in donor-derived
cell-free DNA (dd-cfDNA), a marker of allograft injury, was
observed.
Both stabilization of eGFR, an indicator of kidney function, and
reductions in NK cells, key mediators of downstream inflammation
and tissue damage, were shown relative to placebo.
"There is a large unmet need for a therapy that resolves disease
by the Banff Classification and preserves kidney function in
patients with antibody-mediated rejection," said Principal
Investigator Georg Böhmig,
M.D., Associate Professor of Medicine at
the Division of Nephrology and Dialysis, Department
of Medicine III, Medical University Vienna. "The data
presented in this study are very compelling and represent the
potential for significant progress to be made in this high burden
disease."
According to the United Network for Organ Sharing (UNOS), there
are approximately 93,000 patients on the kidney transplant waitlist
in the United States, with one in
20 patients dying each year while waiting for a transplant. AMR
occurs despite the use of standard immunosuppressive regimens and
is a leading cause of post-transplant kidney failure, impacting
approximately 23,000 transplant recipients in the United States and often leads to
transplant loss. There are currently no approved therapies for late
AMR.
"We believe these data demonstrate the potential for felzartamab
to help preserve the transformative and often life-saving benefit
of a kidney transplant by resolving a leading cause of rejection,"
said Uptal Patel, M.D., Chief
Medical Officer at HI-Bio. "Based on the observed activity and
concurrence of results across key biomarkers of graft damage and
function, we continue to be confident in our anti-CD38 depletion
strategy with felzartamab. We intend to advance felzartamab to
late-stage studies in antibody-mediated rejection and other
immune-mediated diseases, where patients have serious unmet
needs."
The data were simultaneously published in the New England
Journal of Medicine and presented as a late-breaking presentation
by lead author Katharina Mayer,
M.D., of the Division of Nephrology and Dialysis at the Medical
University of Vienna, at the
61st European Renal Association (ERA) Congress in
Stockholm.
The full presentation from the ERA Congress will be made
available on HI-Bio's website.
About Antibody-Mediated Rejection (AMR) in Kidney Transplant
Recipients
Antibody-mediated rejection (AMR) is a major cause of kidney
transplant failure, with chronic AMR affecting ~12% of patients
that receive kidney transplants annually in the
U.S.1 AMR has emerged as the leading cause of late
graft loss in kidney transplant recipients. Effective treatment
options for chronic AMR are currently limited.2
About Felzartamab
Felzartamab is an investigational therapeutic human monoclonal
antibody directed against CD38, a protein expressed on mature
plasma cells. Felzartamab has been shown in clinical studies to
selectively deplete CD38+ plasma cells, which may allow
applications that ultimately improve clinical outcomes in a broad
range of diseases driven by pathogenic antibodies. Felzartamab was
originally developed by MorphoSys AG for multiple myeloma. HI-Bio
exclusively licensed the rights to develop and commercialize
felzartamab across all indications in all countries and territories
excluding China (including
Macau and Hong Kong and Taiwan), where TJ Biopharma retains the
rights.
Felzartamab is an investigational therapeutic candidate that has
not yet been approved by any regulatory authority.
About HI-Bio
Human Immunology Biosciences, Inc. (HI-Bio™), was incubated by ARCH
Venture Partners and Monograph Capital to develop precision
therapies for immune-mediated diseases and to bring clinical
immunology into its next chapter. Inspired by the rise of targeted
therapies in clinical oncology, the company pursues a therapeutic
strategy of targeting and depleting the immune cell types that
drive IMDs. The company's most advanced candidate, felzartamab, is
a CD38-targeted antibody shown in clinical studies to deplete CD38+
cells, including plasma and natural killer (NK) cells, which are
implicated in a range of indications including antibody-mediated
rejection (AMR), IgA nephropathy (IgAN), lupus nephritis (LN) and
primary membranous nephropathy (PMN). Other investors include Alpha
Wave Global, Arkin Bio Capital, Jeito Capital and Viking Global
Investors.
To learn more about HI-Bio, visit www.hibio.com or follow
the company on LinkedIn and X.
References:
- Schinstock et al. (2018) Kidney Transplant with Low Levels of
DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option
for Highly-Sensitized Transplant Candidates (Page 8). Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481511/pdf/nihms837168.pdf#page=8;
Ciancio et al. (2018) Antibody-mediated rejection implies a
poor prognosis in kidney transplantation: Results from a single
center. Available at:
https://onlinelibrary.wiley.com/doi/10.1111/ctr.13392
- Rodriguez-Ramirez et al. (2022) Antibody-mediated
rejection: prevention, monitoring and treatment dilemmas (Page 1).
Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475491/
Contact
|
Morgan
Warners
|
Caroline
Fry
|
FGS Global
|
FGS
Global
|
morgan.warners@fgsglobal.com
|
caroline.fry@fgsglobal.com
|
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