Robust and sustained efficacy in both adult PKD
patients up to 30 months post-RP-L301; first pediatric patient
results suggest efficacy similar to adult cohort with initial
greater than five-point increase in hemoglobin
Sustained genetic correction observed in eight
of 12 evaluable Fanconi Anemia patients, and phenotypic correction
and concomitant hematologic stabilization observed in seven of 12
patients 12-42 months after RP-L102 in Phase 2 pivotal trial
100% overall survival at 12 months post-RP-L201
and favorable safety profile for all LAD-I patients with 12-24
months of follow-up
Robust preclinical proof of concept studies
showed RP-A601 for PKP2-ACM decreased arrhythmias and increased
survival
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading
late-stage biotechnology company advancing an integrated and
sustainable pipeline of genetic therapies for rare disorders with
high unmet need, today announced positive data from the Pyruvate
Kinase Deficiency (PKD), Fanconi Anemia, Severe Leukocyte Adhesion
Deficiency-I (LAD-I) and Danon Disease clinical programs and
PKP2-arrhythmogenic cardiomyopathy (PKP2-ACM) preclinical program
presented at the 26th Annual Meeting of the American Society of
Gene and Cell Therapy (ASGCT) in Los Angeles, California.
“I am pleased that we continue to deliver outstanding clinical
results that highlight the momentum across both our LV hematology
and AAV cardiovascular platforms,” said Jonathan Schwartz, M.D.,
Chief Gene Therapy Officer, Rocket Pharma. “The first pediatric PKD
patient in our Phase 1 trial demonstrated initial hemoglobin
increase of more than five points, and additional patients in our
pivotal Fanconi Anemia trial have demonstrated robust engraftment
and hematologic stabilization. All patients in the LAD-I pivotal
trial continue to demonstrate improvements in clinical parameters.
Regarding RP-A501, as of May 2023, all six patients with ongoing
follow-up in the Danon Phase 1 trial continue to demonstrate
improvements or stabilization at a time when these patients would
most likely experience progressive disease or death.”
Dr. Schwartz continued, “In addition, after recently receiving
IND clearance from the FDA, we are excited to present robust
preclinical proof of concept data from our PKP2-ACM program for the
first time at a scientific meeting. PKP2-ACM is a devastating
disease that is a frequent cause of sudden cardiac death and
represents a significant unmet need given the limited and
non-curative treatment options available to patients. Our data
demonstrate decreased arrhythmias, improved cardiac structure and
function, and increased survival; these results, and our rapid
advancement to the first clinical gene therapy trial for PKP2-ACM,
showcase our proven and consistent ability to elevate gene therapy
research and our dedication to bringing these therapies to patients
who need them most.”
Global Phase 1 Study Results of Lentiviral Mediated Gene
Therapy for Severe Pyruvate Kinase Deficiency (PKD)
The oral presentation includes positive updated data (cut-off
May 3, 2023) from two adult patients followed up to 30 months and
encouraging early data from the first pediatric patient treated
with RP-L301, Rocket’s ex vivo lentiviral gene therapy candidate
for Pyruvate Kinase Deficiency (PKD).
- Robust and sustained efficacy in both adult patients up to 30
months post-infusion demonstrated by normalized hemoglobin (from
baseline levels in the 7.0-7.5 g/dL range), improved hemolysis
parameters, and red blood cell transfusion independence.
- Both adult patients reported improved quality of life with
documented improvements via formal quality of life
assessments.
- The safety profile appears highly favorable, with no
RP-L301-related serious adverse events in either of the adult
patients. Previously reported transient transaminase elevation seen
in both adult subjects post conditioning and infusion with no
clinical stigmata of liver injury have fully resolved.
- Insertion site analyses in peripheral blood and bone marrow in
both adult patients through 24 months post-RP-L301 demonstrated
highly polyclonal patterns and there has been no evidence of
insertional mutagenesis.
- First pediatric results suggest similar efficacy as observed in
long-term efficacy data in the adult cohort.
- The first pediatric patient infusion of RP-L301 was well
tolerated, with engraftment achieved at day +15, hospital discharge
less than one month following infusion, and no RP-L301-related
serious adverse events.
- Hemoglobin normalized six weeks post-infusion and measured 13.4
g/dL at eight weeks (from median baseline of 7.9 g/dL). There were
no red blood cell transfusion requirements following
engraftment.
- Adult and pediatric enrollment is completed in the Phase 1
study. Phase 2 pivotal trial initiation is anticipated in the
fourth quarter of 2023.
Lentiviral-Mediated Gene Therapy for Fanconi Anemia [Group
A]: Results from Global RP-L102 Clinical Trials
The oral presentation includes positive, updated data (cut-off
April 17, 2023) from the ongoing Phase 2 pivotal trial of RP-L102,
Rocket’s ex vivo lentiviral gene therapy candidate for Fanconi
Anemia (FA).
- RP-L102 conferred sustained genetic correction in eight of 12
evaluable patients and comprehensive phenotypic correction in seven
of 12 evaluable patients with ≥12 months of follow up as
demonstrated by increased resistance to mitomycin-C (MMC) in bone
marrow (BM)-derived colony forming cells and hematologic
stabilization.
- The safety profile of RP-L102 remains highly favorable with no
significant safety signals, and the treatment, administered without
any cytotoxic conditioning, continues to be well tolerated. No
signs of bone marrow dysplasia, clonal dominance or insertional
mutagenesis related to RP-L102 have been observed.
- Polyclonal integration patterns have been observed in each of
the seven patients with phenotypic, genetic, and hematologic
evidence of engraftment.
- Pivotal trial enrollment and treatment have been completed, and
the final two patients have been treated with commercial drug
product in preparation for launch.
- Based on the positive efficacy and safety data from the Phase 2
pivotal FA trial, Rocket anticipates filing the Biologics License
Application (BLA) with the FDA in the fourth quarter of 2023.
Autologous Ex Vivo Lentiviral Gene Therapy for Pediatric
Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I):
Interim Results from an Ongoing Phase 1/2 Study
The poster presentation includes positive, updated top-line data
(cut-off November 2, 2022) at 12 to 24 months of follow-up after
RP-L201 infusion for all nine patients. RP-L201 is Rocket’s ex vivo
lentiviral gene therapy candidate for severe Leukocyte Adhesion
Deficiency-I (LAD-I).
- Observed 100% overall survival at 12 months post-infusion via
Kaplan Meier estimate for all nine LAD-I patients with 12 to 24
months of available follow-up. Data also showed evidence of
resolution of LAD-I-related skin rash and restoration of wound
repair capabilities.
- The safety profile of RP-L201 was highly favorable in all
patients with no RP-L201-related serious adverse events to date.
Adverse events related to other study procedures, including
busulfan conditioning, have been previously disclosed and are
consistent with the safety profiles of those agents and
procedures.
- Based on the positive efficacy and safety data from the Phase 2
pivotal LAD-I trial, Rocket anticipates filing the Biologics
License Application (BLA) with the FDA during this second quarter
of 2023.
Danon Disease Phase 1 RP-A501 Results: The First Single-Dose
Intravenous (IV) Gene Therapy with Recombinant Adeno-Associated
Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy
The spotlight oral presentation includes positive, previously
disclosed data (cut-off July 11, 2022) in patients followed for up
to 36 months in the ongoing Phase 1 clinical trial of RP-A501,
Rocket’s investigational AAV gene therapy for Danon Disease. The
presentation includes data from patients treated with the low dose
(6.7 x 1013 GC/kg) in the pediatric (n=2) and adolescent/young
adult (n=3) cohorts, and the high-dose (1.1 x 1014 GC/kg)
adolescent/young adult cohort (n=2).
- As previously disclosed, RP-A501 was associated with favorable
safety at the low dose with an appropriate immunomodulatory
regimen. There have been no RP-A501-related or steroid-related
serious adverse events reported to date in the pediatric
cohort.
- Efficacy results continue to demonstrate sustained improvement
or stabilization in all patients with preserved left ventricular
systolic function at time of treatment (n=6, across all cohorts)
across key clinical, biomarker, echocardiographic, and quality of
life parameters.
- Improvement or stabilization of disease progression in these
patients treated with RP-A501, as measured by natriuretic peptides,
is in direct contrast to progressive worsening observed over three
to 30 months in patients in the prospective natural history
study.
- As of the presentation, all six patients that remain in
follow-up continue to show signs of improvement or stabilization;
additional follow-up data to be provided at a future date.
- The Phase 2 pivotal trial of RP-A501 for Danon Disease remains
on track for initiation during this second quarter of 2023.
Preclinical Efficacy of AAVrh.74-PKP2a (RP-A601): Gene
Therapy for PKP2-associated Arrhythmogenic Cardiomyopathy
The late-breaking abstract presentation includes robust
preclinical proof of concept for RP-A601, Rocket’s investigational
AAV gene therapy for the treatment of arrhythmogenic cardiomyopathy
due to plakophilin 2 pathogenic variants (PKP2-ACM), a devastating
inherited heart disease that can lead to life-threatening
arrhythmias, cardiac structural abnormalities, and sudden cardiac
death. PKP2-ACM affects approximately 50,000 people in the U.S. and
Europe.
- The current standard of care for patients with PKP2-ACM
consists of medical therapy, implantable cardioverter
defibrillators (ICDs), and ablations, which are not curative. Even
with treatment, life-threatening arrhythmias and progression of
disease still occur.
- Preclinical proof of concept from a translationally relevant
animal model has been demonstrated following Rocket-sponsored
studies with academic partners. The preclinical studies with a
cardiomyocyte-specific PKP2 knockout mouse model of ACM evaluated
initial proof of concept and dose-related effects of AAV vectors
(RP-A601), including survival, functional and anatomic benefits.
Notably, the studies evaluated the delivery of RP-A601 at seven-
and 14-days following induction of PKP2 knockout and subsequent
disease onset.
- Results demonstrated increased survival and preserved cardiac
function in the PKP2 knockout mouse model following administration
of RP-A601.
- 100% of adult PKP2 knockout mice receiving RP-A601 seven days
after knockout induction demonstrated survival to the five-month
duration of evaluation, compared to 100% mortality by approximately
day 50 in PKP2 knockout mice receiving formulation control. PKP2
knockout mice receiving RP-A601 displayed preserved ejection
fraction and right ventricular area at 28 days, sustained to five
months.
- Fourteen days following RP-A601 administration, PKP2 knockout
mice demonstrated robust survival with a similar degree of cardiac
benefit through five months. RP-A601 was also associated with
mitigation of isoproterenol-induced premature ventricular
contractions (PVCs) and arrhythmias, which are major morbidity
components of ACM.
- Based on robust preclinical proof of concept that has
demonstrated decreased arrhythmias and increased survival and the
completion of extensive IND-enabling toxicology studies, Rocket has
received IND clearance from the FDA for a Phase 1 study of RP-A601
that will assess the impact of RP-A601 on PKP2 myocardial protein
expression, cardiac biomarkers, and clinical predictors of
life-threatening ventricular arrhythmias and sudden cardiac
death.
- Rocket is initiating Phase 1 study start-up activities and
rapidly advancing the first investigational gene therapy for
PKP2-ACM into the clinic.
About Pyruvate Kinase Deficiency
Pyruvate Kinase Deficiency (PKD) is a rare, monogenic red blood
cell disorder resulting from a mutation in the PKLR gene encoding
for the pyruvate kinase enzyme, a key component of the red blood
cell glycolytic pathway. Mutations in the PKLR gene result in
increased red blood cell destruction and the disorder ranges from
mild to life-threatening anemia. PKD has an estimated prevalence of
4,000 to 8,000 patients in the U.S. and Europe. Children are the
most commonly and severely affected subgroup of patients. Patients
with PKD have a high unmet medical need, as currently available
treatments include splenectomy and red blood cell transfusions,
which are associated with immune defects and chronic iron overload.
Recently, mitapivat, an oral enzyme activator, was approved for use
in adult patients, however its efficacy is limited in more
severely-afflicted patients, most notably in those who are
splenectomized, transfusion-dependent, or whose disease results
from deleterious mutations.
RP-L301 was in-licensed from the Centro de Investigaciones
Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de
Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
(IIS-FJD).
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
Fanconi Anemia complementation group A (FANCA) gene mutation, which
encodes for a protein essential for DNA repair. Mutations in the
FANCA gene leads to chromosomal breakage and increased sensitivity
to oxidative and environmental stress. Increased sensitivity to
DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane
(DEB) is a ‘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 ‘natural 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 cells. There is a high unmet medical need for
patients with FA.
About Leukocyte Adhesion Deficiency-I
Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare,
autosomal recessive pediatric disease caused by mutations in the
ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is
a key protein that facilitates leukocyte adhesion and extravasation
from blood vessels to combat infections. As a result, children with
severe LAD-I are often affected immediately after birth. During
infancy, they suffer from recurrent life-threatening bacterial and
fungal infections that respond poorly to antibiotics and require
frequent hospitalizations. Children who survive infancy experience
recurrent severe infections including pneumonia, gingival ulcers,
necrotic skin ulcers, and septicemia. Without a successful bone
marrow transplant, mortality in patients with severe LAD-I is
60-75% prior to the age of 2 and survival beyond the age of 5 is
uncommon. There is a high unmet medical need for patients with
severe LAD-I.
Rocket’s LAD-I research is made possible by a grant from the
California Institute for Regenerative Medicine (Grant Number
CLIN2-11480). The contents of this press release are solely the
responsibility of Rocket and do not necessarily represent the
official views of CIRM or any other agency of the State of
California.
About Danon Disease
Danon Disease is a rare X-linked inherited disorder caused by
mutations in the gene encoding lysosome-associated membrane protein
2 (LAMP-2), an important mediator of autophagy. This results in
accumulation of autophagosomes and glycogen, particularly in
cardiac muscle and other tissues, which ultimately leads to heart
failure, and for male patients, frequent death during adolescence
or early adulthood. It is estimated to have a prevalence of 15,000
to 30,000 patients in the U.S. and Europe. The only available
treatment option for Danon Disease is cardiac transplantation,
which is associated with substantial complications and is not
considered curative. There are no specific therapies available for
the treatment of Danon Disease. There is a high unmet medical need
for patients with Danon Disease.
About PKP2-Arrhythmogenic Cardiomyopathy (PKP2-ACM)
PKP2-ACM is an inherited heart disease caused by mutations in
the PKP2 gene and characterized by life-threatening ventricular
arrhythmias, cardiac structural abnormalities, and sudden cardiac
death. PKP2-ACM affects approximately 50,000 adults and children in
the U.S. and Europe. Patients living with PKP2-ACM have an urgent
unmet medical need, as current medical, implantable cardioverter
defibrillator (ICD), and ablation therapies do not consistently
prevent disease progression or arrhythmia recurrence, are
associated with significant morbidity including inappropriate
shocks and device and procedure-related complications, and do not
address the underlying pathophysiology or genetic mutation. RP-A601
is being investigated as a one-time, potentially curative gene
therapy treatment that may improve survival and quality of life for
patients affected by this devastating disease.
About Rocket Pharmaceuticals, Inc.
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an
integrated and sustainable pipeline of investigational genetic
therapies designed to correct the root cause of complex and rare
disorders. The Company’s platform-agnostic approach enables it to
design the best therapy for each indication, creating potentially
transformative options for patients afflicted with rare genetic
diseases. Rocket's clinical programs using lentiviral vector (LV)
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, Leukocyte Adhesion Deficiency-I
(LAD-I), a severe pediatric genetic disorder that causes recurrent
and life-threatening infections which are frequently fatal, and
Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell
disorder resulting in increased red cell destruction and mild to
life-threatening anemia. Rocket’s first clinical program using
adeno-associated virus (AAV)-based gene therapy is for Danon
Disease, a devastating, pediatric heart failure condition. Rocket
also has preclinical AAV-based gene therapy programs in
PKP2-arrhythmogenic cardiomyopathy (ACM) and BAG3-associated
dilated cardiomyopathy (DCM). 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 and effectiveness of
product candidates that Rocket is developing to treat Fanconi
Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate
Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the
expected timing and data readouts of Rocket’s ongoing and planned
clinical trials, the expected timing and outcome of Rocket’s
regulatory interactions and planned submissions, Rocket’s plans for
the advancement of its Danon Disease program, including its planned
pivotal trial, 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 “aim,” “anticipate,” "believe," “can,”
“continue,” “design,” “estimate,” "expect," "intend," “may,”
"plan," “potential,” "will give," "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 monitor the impact of COVID-19 on its business
operations and take steps to ensure the safety of patients,
families and employees, the interest from patients and families for
participation in each of Rocket’s ongoing trials, patient
enrollment, trial timelines and data readouts, our expectations
regarding our drug supply for our ongoing and anticipated trials,
actions of regulatory agencies, which may affect the initiation,
timing and progress of pre-clinical studies and clinical trials of
its product candidates, our ability to submit regulatory filings
with the U.S. Food and Drug Administration (FDA) and to obtain and
maintain FDA or other regulatory authority approval of our product
candidates, Rocket’s dependence on third parties for development,
manufacture, marketing, sales and distribution of product
candidates, the outcome of litigation, our competitors’ activities,
including decisions as to the timing of competing product launches,
pricing and discounting, our integration of an acquired business,
which involves a number of risks, including the possibility that
the integration process could result in the loss of key employees,
the disruption of our ongoing business, or inconsistencies in
standards, controls, procedures, or policies, our ability to
successfully develop and commercialize any technology that we may
in-license or products we may acquire and any 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, 2022, filed February 28, 2023
with the SEC and subsequent filings with the SEC including our
Quarterly Reports on Form 10-Q. 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.
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Media Kevin Giordano kgiordano@rocketpharma.com
Investors Brooks Rahmer investors@rocketpharma.com
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