—First Demonstration of Successful Engraftment
of Gene Corrected Hematopoietic Stem Cells Without the Use of
Conditioning—
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (“Rocket”), a
leading U.S.-based multi-platform clinical-stage gene therapy
company, today announces the publication of long-term data from the
ongoing Phase 1/2 trial of RP-L102, the Company’s lentiviral vector
(LVV)-based gene therapy for Fanconi Anemia (FA) in the journal
Nature Medicine. The data included in the manuscript are from the
first four patients treated with RP-L102 in the Phase 1/2
FANCOLEN-I trial that utilized first-generation “Process A” without
the use of any conditioning regimen. Follow-up for each of the
initial four patients was 18-30 months from administration of
RP-L102.
“Data from our first trial of RP-L102 demonstrate increasing
levels of bone marrow engraftment, leading to stabilization and
restored bone marrow function. These data highlight the natural
selective advantage that uniquely exists in FA for gene corrected
stem cells over diseased stem cells, which potentially obviates the
need for conditioning,” said Jonathan Schwartz, M.D., Chief Medical
Officer and Senior Vice President of Rocket. “At the end of the
year, we will have a first look at initial data from our Phase 1
trial of ‘Process B’ RP-L102, which utilizes fresh cells and
incorporates a modified stem cell enrichment process, transduction
enhancers, and commercial-grade vector and final drug product. We
are also excited by the prospect of starting our global
registrational trial incorporating recent alignment on endpoints
from both the U.S. Food and Drug Administration and European
Medicines Agency.”
“There is an increased and urgent need for new therapies for
patients and families suffering from FA as current treatments are
limited to toxic and burdensome bone marrow transplant,” said Paula
Río, Ph.D., Senior Scientist, División de Terapias Innovadoras en
el Sistema Hematopoyético, CIEMAT/CIBERER Unidad Mixta de Terapias
Avanzadas CIEMAT/IIS Fundación Jiménez Díaz, and co-first author of
the manuscript. “We are very pleased to see long-term follow-up
data that further support our thesis for RP-L102 gene therapy
without any conditioning to serve as an innovative, low-toxicity
treatment for the hematologic component of this devastating
disease.”
The data included in the manuscript are from four pediatric
patients (ages 3-6 years) who received RP-L102 utilizing fresh or
cryopreserved CD34+ cells that were collected and transduced.
Patients 02002 and 02006 were treated with higher dose levels of
RP-L102. Patients 02004 and 02005 received non-optimized and lower
doses of RP-L102. Key highlights of the manuscript include:
- Follow-up data for the initial four patients 18-30 months
post-infusion demonstrate progressively increased engraftment in
peripheral blood leukocytes and in the bone marrow following
administration of RP-L102 without the use of conditioning.
- In Patient 02002 at 30 months follow-up, approximately 44% of
bone marrow CD34+ cells displayed gene marking, suggesting the
engraftment of very primitive corrected hematopoietic stem cells
(HSCs).
- Sequential increases in gene marking in peripheral blood and in
the bone marrow for Patients 02004 and 02005 were also seen, but at
more modest levels and after longer durations.
- Phenotypic correction of bone marrow cells was measured by
resistance to mitomycin-C (MMC) in colony forming cells. The bone
marrow resistance to MMC in Patient 02002 increased to 70% at 24
months, approaching the phenotype of a healthy donor. Patients
02004, 02005 and 02006 also displayed progressive increases in MMC
resistance.
- Phenotypic correction of blood cells was measured by
chromosomal stability of T-lymphocytes in the presence of
diepoxybutane (DEB). DEB exposure resulted in a lower proportion of
cells with aberrant chromosomes in Patients 02002, 02004 and
02006.
- Hematologic correction was measured by changes in previously
declining pre-treatment blood count trajectories, which were
evident in at least two peripheral blood lineages for each of the
four patients. Patient 02002 demonstrated stabilized neutrophil
counts and hemoglobin levels as early as six months
post-administration of RP-L102. Similar trends were also seen in
Patient 02006.
- Progressive increases in the total number of corrected
leukocytes were observed shortly after the initial administration
of RP-L102 in all treated patients.
- Favorable safety profile with no serious adverse events
associated with infusion of the investigational product in these
initial four patients.
About Fanconi Anemia
Fanconi Anemia (FA) is a rare pediatric disease characterized by
bone marrow failure, malformations and cancer predisposition. The
primary cause of death among patients with FA is bone marrow
failure, which typically occurs during the first decade of life.
Allogeneic hematopoietic stem cell transplantation (HSCT), when
available, corrects the hematologic component of FA, but requires
myeloablative conditioning. Graft-versus-host disease, a known
complication of allogeneic HSCT, is associated with an increased
risk of solid tumors, mainly squamous cell carcinomas of the head
and neck region. Approximately 60-70% of patients with FA have a
FANC-A gene mutation, which encodes for a protein essential for DNA
repair. Mutation in the FANC-A gene leads to chromosomal breakage
and increased sensitivity to oxidative and environmental stress.
Chromosome fragility induced by DNA-alkylating agents such as
mitomycin-C (MMC) or diepoxybutane (DEB) is the ‘gold standard’
test for FA diagnosis. Somatic mosaicism occurs when there is a
spontaneous correction of the mutated gene that can lead to
stabilization or correction of a FA patient’s blood counts in the
absence of any administered therapy. Somatic mosaicism, often
referred to as ‘nature’s gene therapy’ provides a strong rationale
for the development of FA gene therapy because of the selective
growth advantage of gene-corrected hematopoietic stem cells over FA
cells1.
1Soulier, J.,et al. (2005) Detection of somatic mosaicism and
classification of Fanconi anemia patients by analysis of the
FA/BRCA pathway. Blood 105: 1329-1336
About Rocket Pharmaceuticals, Inc.
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (“Rocket”) is an
emerging, clinical-stage biotechnology company focused on
developing first-in-class gene therapy treatment options for rare,
devastating diseases. Rocket’s multi-platform development approach
applies the well-established lentiviral vector (LVV) and
adeno-associated viral vector (AAV) gene therapy platforms.
Rocket's first two clinical programs using LVV-based gene therapy
are for the treatment of Fanconi Anemia (FA), a difficult to treat
genetic disease that leads to bone marrow failure and potentially
cancer, and Leukocyte Adhesion Deficiency-I (LAD-I), a severe
pediatric genetic disorder that causes recurrent and
life-threatening infections which are frequently fatal. Rocket’s
first clinical program using AAV-based gene therapy is for Danon
disease, a devastating, pediatric heart failure condition. Rocket’s
pre-clinical pipeline programs for bone marrow-derived disorders
are for Pyruvate Kinase Deficiency (PKD) and Infantile Malignant
Osteopetrosis (IMO). For more information about Rocket, please
visit www.rocketpharma.com.
Rocket Cautionary Statement Regarding Forward-Looking
Statements
Various statements in this release concerning Rocket's future
expectations, plans and prospects, including without limitation,
Rocket's expectations regarding the safety, effectiveness and
timing of product candidates that Rocket may develop, to treat
Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I),
Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis
(IMO) and Danon disease, and the safety, effectiveness and timing
of related pre-clinical studies and clinical trials, may constitute
forward-looking statements for the purposes of the safe harbor
provisions under the Private Securities Litigation Reform Act of
1995 and other federal securities laws and are subject to
substantial risks, uncertainties and assumptions. You should not
place reliance on these forward-looking statements, which often
include words such as "believe," "expect," "anticipate," "intend,"
"plan," "will give," "estimate," "seek," "will," "may," "suggest"
or similar terms, variations of such terms or the negative of those
terms. Although Rocket believes that the expectations reflected in
the forward-looking statements are reasonable, Rocket cannot
guarantee such outcomes. Actual results may differ materially from
those indicated by these forward-looking statements as a result of
various important factors, including, without limitation, Rocket's
ability to successfully demonstrate the efficacy and safety of such
products and pre-clinical studies and clinical trials, its gene
therapy programs, the pre-clinical and clinical results for its
product candidates, which may not support further development and
marketing approval, the potential advantages of Rocket's product
candidates, actions of regulatory agencies, which may affect the
initiation, timing and progress of pre-clinical studies and
clinical trials of its product candidates, Rocket's and its
licensors’ ability to obtain, maintain and protect its and their
respective intellectual property, the timing, cost or other aspects
of a potential commercial launch of Rocket's product candidates,
Rocket's ability to manage operating expenses, Rocket's ability to
obtain additional funding to support its business activities and
establish and maintain strategic business alliances and new
business initiatives, Rocket's dependence on third parties for
development, manufacture, marketing, sales and distribution of
product candidates, the outcome of litigation, and unexpected
expenditures, as well as those risks more fully discussed in the
section entitled "Risk Factors" in Rocket's Annual Report on Form
10-K for the year ended December 31, 2018. Accordingly, you should
not place undue reliance on these forward-looking statements. All
such statements speak only as of the date made, and Rocket
undertakes no obligation to update or revise publicly any
forward-looking statements, whether as a result of new information,
future events or otherwise.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190910005368/en/
Claudine Prowse, Ph.D. SVP, Strategy & Corporate Development
Rocket Pharma, Inc. The Empire State Building, Suite 7530 New York,
NY 10118 www.rocketpharma.com investors@rocketpharma.com
Rocket Pharmaceuticals (NASDAQ:RCKT)
Historical Stock Chart
From Mar 2024 to Apr 2024
Rocket Pharmaceuticals (NASDAQ:RCKT)
Historical Stock Chart
From Apr 2023 to Apr 2024