Faster immune reconstitution and decreased rate
of post-transplant viral infection in patients transplanted with
Omisirge versus umbilical cord blood
Gamida Cell Ltd. (Nasdaq: GMDA), a cell therapy pioneer working
to turn cells into powerful therapeutics, today announced the
publication in press of a prospective sub-study of the Phase 3
clinical trial for Omisirge® (omidubicel-onlv), the company’s
allogeneic stem cell transplant therapy, characterizing immune
reconstitution kinetics following hematopoietic stem cell
transplantation (HCT) with Omisirge compared to umbilical cord
blood (UCB). The article appears online on the Transplantation and
Cellular Therapy journal website.
Thirty-seven patients (Omisirge: n=17, UCB: n=20) from 14 global
sites were included in the sub-study and blood samples were
collected from seven to 365 days post-transplantation. Omisirge was
found to facilitate faster immune reconstitution, including natural
killer (NK) cell and helper T (Th) cell reconstitution than UCB
before day 28 post-transplantation. The early reconstitution may
account for the reduced rate of viral infections observed after
transplantation with Omisirge versus UCB.
“The speed of immune reconstitution is critical for patients who
are vulnerable to infection immediately following transplant,” said
Mitchell Horwitz, M.D., senior author of the publication and stem
cell transplant specialist and Professor of Medicine at Duke Cancer
Institute. “These data suggest that Omisirge generates rapid
functional recovery of the immune system, which may be associated
with the lower rate of viral infections observed among patients who
received Omisirge.”
- Omisirge recipients demonstrated an up to 70-fold advantage
over patients who received UCB in median cell counts across most
cell populations, occurring predominantly in the short-term
post-transplantation setting, including NK and T cell
reconstitution in the first two weeks post-transplantation. By
three weeks post-HCT, Omisirge recipients were 3 times more likely
to achieve clinically relevant Th and NK cell counts of 100
cells/µL or above.
- Omisirge recipients received a 33-fold higher median dose of
CD34+ stem cells than UCB recipients. The CD34+ cell content for
recipients transplanted with Omisirge correlated with faster immune
reconstitution by Day 7 post-HCT, which in turn coincided with
earlier hematopoietic recovery.
- Omisirge recipients exhibited superior reconstitution of B
cells, dendritic cells and monocytes.
- Clinical outcomes in this sub-study were consistent with those
from the Phase 3 study for Omisirge. The rate of grade 2/3
infections in the first year were significantly lower with Omisirge
than with UCB: 29% vs 70% for bacterial infections and 6% vs 45%
for viral infections. No differences were reported in incidence of
acute or chronic GVHD between the Omisirge transplanted patients
and the UCB transplanted patients.
“The approval of Omisirge was based on the reduced time to
neutrophil recovery and reduced risk of infection compared to
standard cord blood,” said Ronit Simantov, M.D., Chief Medical and
Scientific Officer of Gamida Cell. "The robust recovery of multiple
immune cell populations we observed provides a potential mechanism
for the reduced incidence of serious bacterial, fungal and viral
infections associated with Omisirge transplantation.”
Stem cell graft source is a known factor influencing immune
reconstitution along with other factors such as patient age,
disease type, preparative chemotherapy regimen and
post-transplantation supportive care.1,2 These data support past
findings that Omisirge stimulates a faster immune response than
standard cord blood.3
The authors noted several limitations to the study, including
sample size. Additionally, there is limited available literature
comparing immune reconstitution by donor source. Although age
variation may influence immune reconstitution outcomes, an
age-adjusted analysis found no age-specific effect.
Omisirge Indication
Omisirge is a nicotinamide modified allogeneic hematopoietic
progenitor cell therapy derived from cord blood indicated for use
in adults and pediatric patients 12 years and older with
hematologic malignancies who are planned for umbilical cord blood
transplantation following myeloablative conditioning to reduce the
time to neutrophil recovery and the incidence of infection.
Important Safety Information for Omisirge
BOXED WARNING: INFUSION REACTIONS, GRAFT VERSUS HOST DISEASE,
ENGRAFTMENT SYNDROME, AND GRAFT FAILURE
- Infusion reactions may be fatal. Monitor patients during
infusion and discontinue for severe reactions. Use is
contraindicated in patients with known allergy to dimethyl
sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin or
bovine material.
- Graft-versus-Host Disease may be fatal. Administration of
immunosuppressive therapy may decrease the risk of GvHD.
- Engraftment syndrome may be fatal. Treat engraftment
syndrome promptly with corticosteroids.
- Graft failure may be fatal. Monitor patients for laboratory
evidence of hematopoietic recovery.
Contraindications
OMISIRGE is contraindicated in patients with known
hypersensitivity to dimethyl sulfoxide (DMSO), Dextran 40,
gentamicin, human serum albumin, or bovine products.
Warnings and Precautions
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of OMISIRGE.
Reactions include bronchospasm, wheezing, angioedema, pruritis and
hives. Serious hypersensitivity reactions, including anaphylaxis,
may be due to DMSO, residual gentamicin, Dextran 40, human serum
albumin (HSA) and bovine material in OMISIRGE. OMISIRGE may contain
residual antibiotics if the cord blood donor was exposed to
antibiotics in utero. Patients with a history of allergic reactions
to antibiotics should be monitored for allergic reactions following
OMISIRGE administration.
Infusion Reactions
Infusion reactions occurred following OMISIRGE infusion,
including hypertension, mucosal inflammation, dysphagia, dyspnea,
vomiting, and gastrointestinal toxicity. Premedication with
antipyretics, histamine antagonists, and corticosteroids may reduce
the incidence and intensity of infusion reactions. In patients
transplanted with OMISIRGE in clinical trials, 47% (55/117)
patients had an infusion reaction of any severity. Grade 3-4
infusion reactions were reported in 15% (18/117) patients. Infusion
reactions may begin within minutes of the start of infusion of
OMISIRGE, although symptoms may continue to intensify and not peak
for several hours after the completion of the infusion. Monitor
patients for signs and symptoms of infusion reactions during and
after OMISIRGE administration. When a reaction occurs, pause the
infusion and institute supportive care as needed.
Graft-versus-Host Disease
Acute and chronic GvHD, including life-threatening and fatal
cases, occurred following treatment with OMISIRGE. In patients
transplanted with OMISIRGE Grade II-IV acute GvHD was reported in
58% (68/117). Grade III- IV acute GvHD was reported in 17%
(20/117). Chronic GvHD occurred in 35% (41/117) of patients. Acute
GvHD manifests as maculopapular rash, gastrointestinal symptoms,
and elevated bilirubin. Patients treated with OMISIRGE should
receive immunosuppressive drugs to decrease the risk of GvHD, be
monitored for signs and symptoms of GvHD, and treated if GvHD
develops.
Engraftment Syndrome
Engraftment syndrome may occur because OMISIRGE is derived from
umbilical cord blood. Monitor patients for unexplained fever, rash,
hypoxemia, weight gain, and pulmonary infiltrates in the
peri-engraftment period. Treat with corticosteroids as soon as
engraftment syndrome is recognized to ameliorate symptoms. If
untreated, engraftment syndrome may progress to multiorgan failure
and death.
Graft Failure
Primary graft failure occurred in 3% (4/117) of patients in
OMISIRGE clinical trials. Primary graft failure, which may be
fatal, is defined as failure to achieve an absolute neutrophil
count greater than 500 per microliter blood by Day 42 after
transplantation. Immunologic rejection is the primary cause of
graft failure. Monitor patients for laboratory evidence of
hematopoietic recovery.
Malignancies of Donor Origin
Two patients treated with OMISIRGE developed post-transplant
lymphoproliferative disorder (PTLD) in the second-year
post-transplant. PTLD manifests as a lymphoma-like disease favoring
non-nodal sites. PTLD is usually fatal if not treated. The etiology
is thought to be donor lymphoid cells transformed by Epstein-Barr
virus (EBV). Serial monitoring of blood for EBV DNA may be
warranted in patients with persistent cytopenias. One patient
treated with OMISIRGE developed a donor-cell derived
myelodysplastic syndrome (MDS) during the fourth-year
post-transplant. The natural history is presumed to be the same as
that for de novo MDS. Monitor life-long for secondary malignancies.
If a secondary malignancy occurs, contact Gamida Cell at (844)
477-7478.
Transmission of Serious Infections
Transmission of infectious disease may occur because OMISIRGE is
derived from umbilical cord blood. Disease may be caused by known
or unknown infectious agents. Donors are screened for increased
risk of infection, clinical evidence of sepsis, and communicable
disease risks associated with xenotransplantation. Maternal and
infant donor blood is tested for evidence of donor infection. See
full Prescribing Information, Warnings and Precautions,
Transmission of Serious Infections for list of testing performed.
OMISIRGE is tested for sterility, endotoxin, and mycoplasma. There
may be an effect on the reliability of the sterility test results
if the cord blood donor was exposed to antibiotics in utero.
Product manufacturing includes bovine-derived reagents. All
animal-derived reagents are tested for animal viruses, bacteria,
fungi, and mycoplasma before use. These measures do not eliminate
the risk of transmitting these or other transmissible infectious
diseases and disease agents. Test results may be found on the
container label and/or in accompanying records. If final
sterility results are not available at the time of use, Quality
Assurance will communicate any positive results from sterility
testing to the physician. Report the occurrence of transmitted
infection to Gamida Cell at (844) 477-7478.
Transmission of Rare Genetic Diseases
OMISIRGE may transmit rare genetic diseases involving the
hematopoietic system because it is derived from umbilical cord
blood. Cord blood donors have been screened to exclude donors with
sickle cell anemia, and anemias due to abnormalities in hemoglobins
C, D, and E. Because of the age of the donor at the time cord blood
collection takes place, the ability to exclude rare genetic
diseases is severely limited.
ADVERSE REACTIONS
The most common adverse reactions (incidence > 20%) are
infections, GvHD, and infusion reaction.
Please see full Prescribing Information,
including Boxed Warning.
About the Omisirge Phase 3 Study
In a global, randomized Phase 3 clinical study (NCT02730299),
Omisirge demonstrated a median time to neutrophil recovery of 12
days in the intent to treat population, compared to 22 days for
standard cord blood (p<0.001).4 Incidence of Grade 2/3 bacterial
or Grade 3 fungal infections through 100 days following
transplantation occurred in 39% of patients in the Omisirge arm and
60% of patients in the standard cord blood arm.1 The full Phase 3
clinical study results are available in Blood, the official journal
of the American Society of Hematology. The safety profile for
Omisirge is consistent with the expected adverse events of
allogeneic hematopoietic stem cell transplantation following
myeloablative conditioning. Among 117 patients who received
Omisirge for any disease, infusion reactions occurred in 47% of
patients (Grade 3 or 4 in 15%), acute graft-versus-host disease
(GvHD) in 58% (Grade III-IV in 17%), chronic GvHD in 35% and graft
failure in 3%.5
About Gamida Cell
Gamida Cell is a cell therapy pioneer working to turn cells into
powerful therapeutics. The company’s proprietary nicotinamide (NAM)
technology leverages the properties of NAM to enhance and expand
cells, creating allogeneic cell therapy products and candidates
that are potentially curative for patients with hematologic
malignancies. These include Omisirge®, an FDA-approved nicotinamide
modified allogeneic hematopoietic progenitor cell therapy, and
GDA-201, an intrinsic NK cell therapy candidate being investigated
for the treatment of hematologic malignancies. For additional
information, please visit www.gamida-cell.com or follow Gamida Cell
on LinkedIn, Facebook, Twitter and Instagram.
Omisirge® is a registered trademark of Gamida Cell Inc. © 2023
Gamida Cell Inc. All Rights Reserved.
Cautionary Note Regarding Forward Looking Statements
This press release contains forward-looking statements as that
term is defined in the Private Securities Litigation Reform Act of
1995, including with respect to the potentially life-saving or
curative therapeutic and commercial potential of Omisirge®
(omidubicel-onlv). Any statement describing Gamida Cell’s goals,
expectations, financial or other projections, intentions or beliefs
is a forward-looking statement and should be considered an at-risk
statement. Such statements are subject to a number of risks,
uncertainties and assumptions including those related to clinical,
scientific, regulatory and technical developments and those
inherent in the process of developing and commercializing product
candidates that are safe and effective for use as human
therapeutics. In light of these risks and uncertainties, and other
risks and uncertainties that are described in the Risk Factors
section and other sections of Gamida Cell’s Quarterly Report on
Form 10-Q, filed with the Securities and Exchange Commission (SEC)
on May 15, 2023, and other filings that Gamida Cell makes with the
SEC from time to time (which are available at www.sec.gov), the
events and circumstances discussed in such forward-looking
statements may not occur, and Gamida Cell’s actual results could
differ materially and adversely from those anticipated or implied
thereby. Although Gamida Cell’s forward-looking statements reflect
the good faith judgment of its management, these statements are
based only on facts and factors currently known by Gamida Cell. As
a result, you are cautioned not to rely on these forward-looking
statements.
__________________________
1 Mackall C, Fry T, Gress R, et al. Background to hematopoietic
cell transplantation, including post-transplant immune recovery.
Bone Marrow Transplant. 2009;44:457-462.
https://doi.org/10.1038/bmt.2009.255.
2 Storek, J., Dawson, M. A., Storer, B., Stevens-Ayers, T.,
Maloney, D. G., Marr, K. A., Witherspoon, R. P., Bensinger, W.,
Flowers, M. E., Martin, P., Storb, R., Appelbaum, F. R., &
Boeckh, M. (2001). Immune reconstitution after allogeneic marrow
transplantation compared with blood stem cell transplantation.
Blood, 97(11), 3380–3389.
https://doi.org/10.1182/blood.v97.11.3380
3 De Koning C., Tao W., Lacna A., van Veghel K., Horwitz M.E.,
Sanz G., Jagasia M.H., Wagner J.E., Stiff P.J., Hanna R., et al.
Lymphoid and myeloid immune cell reconstitution after
nicotinamide-expanded cord blood transplantation. Bone Marrow
Transplant. 2021:1–8. doi: 10.1038/s41409-021-01417-4.
4 Horwitz, M. E., Stiff, P. J., Cutler, C., Brunstein, C.,
Hanna, R., Maziarz, R. T., Rezvani, A. R., Karris, N. A., McGuirk,
J., Valcarcel, D., Schiller, G. J., Lindemans, C. A., Hwang, W. Y.,
Koh, L. P., Keating, A., Khaled, Y., Hamerschlak, N., Frankfurt,
O., Peled, T., … Sanz, G. (2021). Omidubicel vs standard
myeloablative umbilical cord blood transplantation: Results of a
phase 3 randomized study. Blood, 138(16), 1429–1440.
5 Omisirge [package insert]. Boston, MA: Gamida Cell; 2023.
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