SAN RAFAEL, Calif.,
May 12, 2021 /PRNewswire/
-- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced
three oral and three poster presentations on valoctocogene
roxaparvovec, an investigational gene therapy for the treatment of
adults with severe hemophilia A at the American Society of Gene and
Cell Therapy (ASGCT) Virtual 2021 Annual Meeting being held May
11-14. These six presentations advance the scientific
understanding of the potential of valoctocogene roxaparvovec to
treat people with hemophilia A.
"BioMarin is committed to furthering our scientific
understanding of gene therapy through our experience developing
valoctocogene roxaparvovec. This foundation of knowledge will help
to inform the development of other gene therapies in our
pipeline. The studies presented at ASGCT illustrate our
continued quest to define who responds to treatment, why, and for
how long. Vector catabolism remains the leading hypothesis as
to why Factor VIII expression evolves over time, highlighting
pathways to improve patient outcomes," said Lon Cardon, Ph.D., Senior Vice President, Chief
Scientific Strategy Officer at BioMarin. "Our
presentations at ASGCT extend our nearly decade-long experience in
AAV scientific and clinical research to improve our understanding
of the critical features of vectors, promoters, pharmacologic
agents, and manufacturing technologies to help us deliver
potentially transformative treatments to people with rare genetic
disease."
The oral presentation, Investigating Mechanisms of
Variability of AAV5-hFVIII-SQ Expression in Mice, provide new
insights into inter-individual differences in Factor VIII
expression of regulatory molecules involved in transduction,
transcription and protein folding/secretion, as well as advance the
understanding of factors that may impact variability in transgene
expression. BioMarin is conducting multiple ongoing in vitro
and in vivo studies to further investigate the mechanistic drivers
of AAV5 gene therapy variability.
The oral presentation, Long-Term Expression Comparison of
Adeno-Associated Virus (AAV) Vector Produced in HEK293 vs Sf Cell
Lines, compares the durability of transgene expression in mice
using vectors produced in mammalian cell production systems or
baculovirus—Spodoptera frugiperda (Sf) insect-cell systems—and
showed comparable long-term durability of transgene expression by
week 12 through week 57 with no difference between HEK293- vs
Sf-produced groups.
The poster presentation, Rare Genomic Integrations of
AAV5-hFVIII-SQ Occur without Evidence of Clonal Activation or
Gene-Specific Targeting, showed that in liver samples from
non-human primates, 13 or 26 weeks after vector administration, the
vast majority of AAV5-FVIII-SQ vector or valoctocogene roxaparvovec
(>99.9%) showed no signs of integration, consistent with a
predominantly episomal presence. Rare vector integration events
occurred on average in less than 1 in 600 liver cells, which is in
line with expectations for AAV vectors and several orders of
magnitude lower than the natural mutation rate in the general
population. There was no evidence of clonal expansion, suggesting
that individual integration sites were restricted to single cells
or small groups of progeny cells. BioMarin supports
continuous scientific evaluations to better characterize
integration profiles across AAV gene therapy products.
BioMarin's presentations at ASGCT include:
Platform Presentations
Investigating Mechanisms of Variability of AAV5-hFVIII-SQ
Expression in Mice
Bridget Yates
BioMarin Pharmaceutical Inc., Novato,
CA, USA
Wednesday, May
12 · 6:30 – 6:45
pm
Long-Term Expression Comparison of Adeno-Associated Virus (AAV)
Vector Produced in HEK293 vs Sf Cell Lines
Britta Handyside, PhD
BioMarin Pharmaceutical Inc., Novato,
CA, USA
Wednesday, May
12 · 7:15 – 7:30
pm
Lack of Germline Transmission in Male Mice Following
Administration of AAV5-hFVIII-SQ, an Investigational Gene Therapy
for Hemophilia A
Cheng Su, PhD
BioMarin Pharmaceutical Inc., Novato,
CA, USA
Friday, May 14
· 1:00 – 1:15 pm
Poster Sessions
Poster
#
|
Title &
Authors
|
338
|
The Effect of
Prophylactic Corticosteroid Treatment on Adeno-Associated Virus
(AAV)-Mediated Gene Expression
Handyside B, Zhang L,
Yates B, Xie L, Kaplowitz B, Gorostiza O, Murphy R, Fredette N,
Baridon B, Ngo K, Siso S, Agrawal V, Cortesio C, Akeefe H,
Woloszynek J, Zhang W, Su C, Colosi P, Bullens S, Veres G, Bunting
S, Fong S
|
892
|
Ultra-Sensitive AAV
Capsid Detection by Immunocapture-Based Quantitative Polymerase
Chain Reaction Following Factor VIII Gene Transfer
Sandza K, Clark A,
Koziol E, Akeefe H, Yang F,
Holcomb J, Patton K, Hammon K, Mitchell N, Wong W, Zoog S, Kim B,
Henshaw J, Vettermann C
|
895
|
Rare Genomic
Integrations of AAV5-hFVIII-SQ Occur without Evidence of Clonal
Activation or Gene-Specific Targeting
Sullivan L, Zahn M, Gil
Farina I, Kasprzyk T, O'Neill C, Eggan K, Zoog S, Veres G, Schmidt
M, Vettermann C
|
Regulatory Status
In Europe, BioMarin plans to
submit a Marketing Authorization Application (MAA) for
valoctocogene roxaparvovec for the treatment of severe hemophilia A
with one-year results from the Phase 3 GENEr8-1 study to the
European Medicines Agency (EMA) in June
2021.
In the United States, BioMarin
plans to submit two-year follow-up safety and efficacy data on all
study participants from the GENEr8-1 study to support the
benefit/risk assessment of valoctocogene roxaparvovec. BioMarin is
targeting a Biologics License Application (BLA) submission in the
second quarter of 2022 assuming favorable study results, followed
by an expected six-month review procedure by the FDA.
The FDA granted Regenerative Medicine Advanced Therapy (RMAT)
designation to valoctocogene roxaparvovec in March 2021. RMAT is an expedited program intended
to facilitate development and review of regenerative medicine
therapies, such as valoctocogene roxaparvovec, that are intended to
address an unmet medical need in patients with serious conditions.
The RMAT designation is complementary to Breakthrough Therapy
Designation, which the Company received in 2017, allowing early,
close, and frequent interactions with the FDA.
In addition to the RMAT Designation and Breakthrough Therapy
Designation, BioMarin's valoctocogene roxaparvovec also has
received orphan drug designation from the FDA and EMA for the
treatment of severe hemophilia A. The Orphan Drug Designation
program is intended to advance the evaluation and development of
products that demonstrate promise for the diagnosis and/or
treatment of rare diseases or conditions.
Robust Clinical Program
BioMarin has multiple clinical studies underway in its
comprehensive gene therapy program for the treatment of severe
hemophilia A. In addition to the global Phase 3 study
GENEr8-1 and the ongoing Phase 1/2 dose escalation study, the
Company is actively enrolling participants in a Phase 3b, single arm, open-label study to evaluate the
efficacy and safety of valoctocogene roxaparvovec at a dose of 6e13
vg/kg with prophylactic corticosteroids in people with hemophilia
A. The Company is running a Phase 1/2 Study with the
6e13kg/vg dose of valoctocogene roxaparvovec in approximately 10
participants with pre-existing AAV5 antibodies, as well as another
Phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene
roxaparvovec in people with hemophilia A with active or prior FVIII
inhibitors.
Gene Therapy Manufacturing
BioMarin has leveraged its knowledge and experience in
manufacturing complex biological products to design, construct and
validate a state-of-the-art vector production facility in
Novato, California. This
facility is the site of production for both valoctocogene
roxaparvovec and BMN 307, an investigational gene therapy to treat
Phenylketonuria. Manufacturing capabilities are an essential driver
for BioMarin's gene therapy programs and allows the Company to
control quality, capacity, costs and scheduling enabling rapid
development. Production of gene therapies with a commercial ready
process at scale reduces risk associated with making process
changes later in development and may speed overall development
timelines significantly.
Ongoing process development efforts and experience gained at
commercial scale have led to improvements in productivity and
operational efficiency. The ability to scale out the facility
with additional equipment combined with the improvements in
productivity result in a doubling of overall potential capacity to
10,000 doses per year, combined for both products, depending on
final dose and product mix. This improvement in productivity is
anticipated to meet potential commercial and clinical demand for
both valoctocogene roxaparvovec and BMN 307 well into the
future.
About Hemophilia A
People living with hemophilia A lack sufficient functioning
Factor VIII protein to help their blood clot and are at risk for
painful and/or potentially life-threatening bleeds from even modest
injuries. Additionally, people with the most severe form of
hemophilia A (FVIII levels <1%) often experience painful,
spontaneous bleeds into their muscles or joints. Individuals
with the most severe form of hemophilia A make up approximately 50
percent of the hemophilia A population. People with
hemophilia A with moderate (FVIII 1-5%) or mild (FVIII 5-40%)
disease show a much-reduced propensity to bleed. The standard
of care for individuals with severe hemophilia A is a prophylactic
regimen of replacement Factor VIII infusions administered
intravenously up to two to three times per week or 100 to 150
infusions per year. Despite these regimens, many people
continue to experience breakthrough bleeds, resulting in
progressive and debilitating joint damage, which can have a major
impact on their quality of life.
Hemophilia A, also called Factor VIII deficiency or classic
hemophilia, is an X-linked genetic disorder caused by missing or
defective Factor VIII, a clotting protein. Although it is passed
down from parents to children, about 1/3 of cases are caused by a
spontaneous mutation, a new mutation that was not inherited.
Approximately 1 in 10,000 people have Hemophilia A.
About BioMarin
BioMarin is a global biotechnology company that develops and
commercializes innovative therapies for serious and
life-threatening rare and ultra-rare genetic diseases. The
Company's portfolio consists of six commercialized products and
multiple clinical and pre-clinical product candidates. For
additional information, please visit www.biomarin.com.
Information on BioMarin's website is not incorporated by reference
into this press release.
Forward Looking Statements
This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc., including
without limitation, statements about the potential of valoctocogene
roxaparvovec to treat people with hemophilia A, the foundation of
knowledge from these studies will help to inform the development of
other gene therapies in our pipeline, , our experience in AAV
scientific and clinical research helping us to deliver potentially
transformative treatments, , the Company's plans to submit an
MAA to EMA in June 2021, the
Company's plans to submit two-year follow-up safety and efficacy
data on all study participants from the GENEr8-1 study to the FDA,
the Company targeting a BLA submission to the FDA in the second
quarter of 2022 followed by an expected six-month review procedure
by the FDA and statements about the overall potential capacity of
our vector production manufacturing facility in Novato to produce 10,000 doses per year,
depending on final dose and product mix, and the anticipation that
this capacity will meet potential commercial and clinical demand
for both valoctocogene roxaparvovec and BMN 307 well into the
future. These forward-looking statements are predictions and
involve risks and uncertainties such that actual results may differ
materially from these statements. These risks and uncertainties
include, among others: results and timing of current and planned
preclinical studies and clinical trials of valoctocogene
roxaparvovec, including final analysis of data from the
continuation of these trials; any potential adverse events observed
in the continuing monitoring of the patients in the clinical
trials; the content and timing of decisions by the FDA, the EMA and
other regulatory authorities; the content and timing of decisions
by local and central ethics committees regarding the clinical
trials; our ability to successfully manufacture the product
candidate for the preclinical and clinical trials; and those
other risks detailed from time to time under the caption "Risk
Factors" and elsewhere in BioMarin's Securities and Exchange
Commission (SEC) filings, including without limitation, BioMarin's
Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, as such factors may be updated by
any subsequent reports. BioMarin undertakes no duty or obligation
to update any forward-looking statements contained in this press
release as a result of new information, future events or changes in
its expectations.
BioMarin® is a registered trademark of BioMarin Pharmaceutical
Inc.
Contacts:
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|
Investors
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Media
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Traci
McCarty
|
Debra
Charlesworth
|
BioMarin
Pharmaceutical Inc.
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BioMarin
Pharmaceutical Inc.
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(415)
455-7558
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(415)
455-7451
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SOURCE BioMarin Pharmaceutical Inc.