— Pediatric efficacy data for both
patients show initial improvements across clinical, functional and
biomarker endpoints with six to nine months of follow-up; positive
results including protein expression obtained at three and six
months consistent with adult cohorts at similar timeframe—
— Results demonstrate sustained clinical
benefit across all parameters in adult patients with up to 36
months of follow-up—
— All adult and pediatric patients with closely
monitored immunomodulatory regimen showed improvement in New York
Health Association (NYHA) class (from II to I) with follow-up of
six to 36 months; patients are no longer afflicted with cardiac
disease symptoms during regular activity or cardiac-related
limitations in physical activity—
— RP-A501 was generally well tolerated with
manageable safety profile across pediatric and adult cohorts—
— Strength of clinical data presented to date
expected to support Phase 2 pivotal study; FDA feedback on pivotal
study design and endpoints anticipated later this year—
— Webcast to be held at 8:00 a.m. ET today,
Sept. 30—
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading
late-stage biotechnology company advancing an integrated and
sustainable pipeline of investigational genetic therapies for rare
childhood disorders with high unmet need, today announces positive
clinical updates from its Phase 1 Danon Disease Trial for RP-A501
through an oral poster session at the Heart Failure Society of
America (HFSA) Annual Scientific Meeting 2022. This includes
updated safety and efficacy data from patients in the pediatric and
adult cohorts which demonstrate that RP-A501 was generally well
tolerated and conferred clinical benefit.
“Today’s Danon Disease trial results, the most comprehensive
investigational gene therapy dataset for any cardiac condition,
demonstrate positive early findings in pediatric patients and
continued robust activity in adults that represent potential
freedom from the devastating effects of this disease, including
those that lead to heart transplantation or death,” said Gaurav
Shah, M.D., Chief Executive Officer of Rocket Pharma. “Results
showed RP-A501 was generally well tolerated with evidence of
durable treatment effect and improvement of Danon Disease,
including for both pediatric patients with up to nine months of
follow-up and four adult patients with up to 36 months of
follow-up. Further, efficacy data from the pediatric patients are
following similar or more favorable positive trends as in the
adults at a similar timeframe. Pediatric patients showed vacuole
clearance and marked reductions in brain natriuretic peptide (BNP)
and troponin. We also observed improvement in New York Heart
Association (NYHA) class and early improvements in the Kansas City
Cardiomyopathy Questionnaire (KCCQ) for both patients.”
Dr. Shah continued, “Data collected in adults from biomarker,
clinical and functional parameters trend towards improvement in the
initial months following gene therapy and appear durable for two to
three years after treatment. I am particularly excited that five
out of five currently enrolled pediatric and adult patients with a
closely monitored immunomodulatory regimen showed improvement in
NYHA class (from II to I) with a follow-up of six to 36 months.
Simply put, these data indicate that these patients are no longer
afflicted with cardiac disease symptoms during regular activity or
cardiac-related limitations in physical activity. In this
devastating disease with markedly shortened life span,
stabilization alone may be considered meaningful, so the sustained
improvements we’ve seen exceed our expectations and could be
transformative for patients receiving gene therapy.”
“Taken together, we believe the totality of data from the six
patients currently enrolled in the Phase 1 trial will support
advancement toward a Phase 2 pivotal study,” said Dr. Shah. “We
recently convened an advisory board of international experts who
endorsed our planned Phase 2 study design and endpoints, and we
look forward to further discussions with the FDA later this
year.”
Safety Profile of the First Pediatric Cardiomyopathy Gene
Therapy Trial: RP-A501 (AAV9:LAMP2B) for Danon Disease and Extended
Results from Phase 1
The data described in this oral poster presentation (data
cut-off September 27, 2022, with source data verification through
July 11, 2022) and in this press release are from the ongoing
first-in-human Phase 1 clinical trial evaluating a single
intravenous infusion of RP-A501, the Company’s investigational gene
therapy for the treatment of Danon Disease. The presentation
includes early efficacy data with updated safety data from the
low-dose (6.7 x 1013GC/kg; n=2) pediatric cohort, as well as
updated efficacy and safety data from young adult and adolescent
patients in the low-dose (6.7 x 1013 GC/kg; n=3) and high-dose (1.1
x 1014 GC/kg; n=2) cohorts.
- Early pediatric efficacy data are consistent with initial
improvements observed in adult patients at a similar timeframe of
up to nine months follow-up and sustained clinical benefit across
biomarker, clinical and functional parameters in currently enrolled
adult patients at 24 to 36 months of follow-up.
- Gene expression: In the pediatric cohort, LAMP2B gene
expression by immunohistochemistry was 21.1% in patient 1008 at six
months and 34.7% in patient 1009 at three months. Evidence of
durable and meaningful cardiac LAMP2B protein expression as read at
a centralized core lab was achieved in all patients across
pediatric and adult cohorts at three months and sustained through
six to nine months in the pediatric cohort and 24 months in the
adult cohorts in patients with a closely monitored immunomodulatory
regimen.
- The following assays were performed, validated and reported for
patients with at least six months of follow-up.
- Vacuolar area: In the first pediatric patient (1008),
vacuolar area as assessed by an automated method in representative
biopsy samples was found to have decreased by 77% at six months.
Six-month biopsy results are not yet available for the second
pediatric patient (1009). All adult patients have also seen
meaningful decreases in vacuolar area ranging from 26% to 74% at
most recent available timepoints.
- Brain natriuretic peptide (BNP): In the pediatric
cohort, BNP, a key marker of heart failure, decreased from a
pretreatment baseline by 78% in patient 1008 at nine months and by
62% in patient 1009 at six months. All patients in the pediatric
and adult cohorts showed stabilization or meaningful decreases in
BNP, with the most dramatic increases observed in patients with
higher baseline BNP (90% for patient 1002 in the adult cohort at 30
months and 78% for patient 1008 in the pediatric cohort at nine
months). Adult patients demonstrated reduction in BNP of greater
than 75% from mean pretreatment baseline compared to mean values at
18 to 24 month timepoints.
- Troponin: The pediatric patients, despite a more limited
six and nine months of follow-up, were observed to have meaningful
decreases in high sensitivity troponin I (hsTnI), a protein in the
blood showing signs of cardiac injury, of 90% and 85%,
respectively. Patients in the adult cohorts demonstrated
significant decreases in hsTnI. Notably, the four adult patients
were observed to have a reduction in troponin of greater than 75%
from mean pretreatment baseline to mean values at 18 to 24 months
that was sustained in the three adult patients who are currently 30
to 36 months post-treatment.
- New York Heart Association (NYHA) Class: In the
pediatric cohort, an improvement (from Class II to I) in NYHA
class, a measure of the symptoms and functional limitations
resulting from heart failure, was observed in both patients. In the
adult cohorts, all three patients treated with a closely monitored
immunomodulatory regimen showed improvement in NYHA class (from II
to I). Stabilization of NYHA class was observed in one adult
patient treated at the low dose without a closely monitored
regimen.
- Kansas City Cardiomyopathy Questionnaire (KCCQ):
Patients in the pediatric cohort showed significant improvement in
KCCQ Overall Score, a measure (0-100) of physical and social
limitations, symptoms and quality of life in patients with heart
failure. Specifically, patient 1008 demonstrated improvement from a
pretreatment baseline of 50 to 93 at nine months and patient 1009
demonstrated improvement from a pretreatment baseline of 52 to 81
at three months. All patients treated in pediatric and adult
cohorts with a closely monitored immunomodulatory regimen showed
improvements ranging between three and 43 points when comparing
baseline to the most recent available timepoint.
- Left ventricular (LV) wall thickness: In the pediatric
cohort, patient 1008 demonstrated reduction in maximum LV wall
thickness by 3% from treatment baseline after six months of
follow-up. In the adult cohort, all four patients demonstrated a
reduction of greater than 15% and greater than 20% from mean
baseline in both LV posterior wall thickness in diastole and
maximum LV wall thickness, respectively, compared to mean values at
18 to 24 months, which represents improvement of the ventricular
hypertrophy.
- RP-A501 was observed to be generally well tolerated at the low
dose with a manageable safety profile across pediatric and adult
cohorts.
- In the pediatric cohort, RP-A501 was well tolerated in both
patients with six to eleven months follow-up. The patients were
observed to have normal-range platelets, minimal complement
activation and no complement-related adverse events. The two
patients received a modified immunomodulatory regimen to mitigate
adverse events. No significant immediate or delayed toxicities,
significant skeletal myopathy, or late transaminase elevations have
been observed to date.
- Taken together, these results are consistent with a positive
benefit/risk profile for RP-A501 in Danon Disease.
- Phase 1 enrollment and treatment are complete.
- RP-A501 together with the enhanced immunomodulatory regimen
appears well tolerated and effective in the pediatric cohort.
- In the adult cohort, RP-A501 stabilizes and potentially
improves Danon Disease cardiomyopathy.
- Early pediatric data are encouraging and consistent with
improvements at similar or earlier timepoints compared to the adult
cohorts.
- Findings are supportive of Phase 2 evaluation of RP-A501 in
Danon Disease.
Investor Webcast Information
Company management will discuss the Danon Disease data via
webcast today, Sept. 30, 2022, at 8:00 a.m. ET. To access the
webcast, please register online at:
https://ir.rocketpharma.com/events-presentations. Participants are
requested to register a minimum of 15 minutes before the start of
the call.
A simultaneous webcast of the presentation will be available
under “Events” in the Investors section of the Company’s website
at: https://ir.rocketpharma.com/. The webcast replay will be
available on the Rocket website upon completion of the event.
About RP-A501
RP-A501 is an investigational gene therapy product being
developed for Danon Disease and the first potential gene therapy
for monogenic heart failure. It consists of a recombinant
adeno-associated serotype 9 (AAV9) capsid containing a functional
version of the human LAMP2B transgene (AAV9.LAMP2B). RP-A501 is
currently being evaluated in a Phase 1 clinical trial; preliminary
data from this study’s low-dose cohort showed that RP-A501 was
generally well tolerated and conferred evidence of improved cardiac
function.
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.
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
childhood 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 (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, 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. 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 its guidance for 2022, the safety
and effectiveness of RP-A501 for the potential treatment of Danon
Disease, trends for RP-A501 safety and efficacy based on the adult
patients treated to date, the expected timing and outcome of
Rocket’s regulatory interactions and planned submissions, including
in connection with the potential advancement toward a Phase 2
pivotal study for RP-A501, Rocket’s plans for the advancement of
its Danon Disease program 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 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, our expectations
regarding the delays and impact of COVID-19 on clinical sites,
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, 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, 2021, filed
February 28, 2022 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220930005139/en/
Media Kevin Giordano Director, Corporate Communications
kgiordano@rocketpharma.com
Investors Jessie Yeung, M.B.A. Vice President, Investor
Relations and Corporate Finance investors@rocketpharma.com
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