SAN RAFAEL, Calif.,
July 8, 2019 /PRNewswire/ -- BioMarin
Pharmaceutical Inc. (NASDAQ: BMRN) announced today that based on
recent meetings with health authorities in the U.S. and
Europe, the company plans to
submit marketing applications to both the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency (EMA) in 4Q
2019 for its investigational gene therapy, valoctocogene
roxaparvovec, for adults with severe hemophilia A. These
submissions will be based on the updated three-year Phase 1/2 data
and the recently completed Phase 3 interim analysis of patients
treated with material from the to-be-commercialized process.
Both submissions are expected to represent the first time a gene
therapy product for any type of hemophilia will be reviewed for
marketing authorization by health authorities.
Both the FDA and EMA continue to prioritize interactions related
to the review of valoctocogene roxaparvovec through the
Breakthrough Therapy Designation program in the U.S and the
Priority Medicines (PRIME) regulatory initiative in Europe. Valoctocogene roxaparvovec is
one of the first therapies to go through the new PRIME
initiative. FDA and EMA grant expedited review designations
for investigational therapies that address unmet medical needs in
the treatment of a serious condition and/or show the potential to
offer major therapeutic advantages over existing
treatments.
"People with severe hemophilia A continue to experience
clinically relevant breakthrough bleeds despite the current
standard of care and can be limited in their physical activities,"
said Professor John Pasi, M.B.,
Ch.B., Ph.D., from Barts and the London School of Medicine and
Dentistry; the chief investigator for the valoctocogene
roxaparvovec Phase 1/2 study and a principal investigator for the
Phase 3 study. "Valoctocogene roxaparvovec represents a
potentially transformative investigative therapy that could improve
patients' quality of life, including consequences of bleeding,
physical functioning, role functioning, emotional impact, treatment
concern, and worry."
"We applaud the FDA's efforts to incorporate the patient voice
in the regulatory review process. Powerful and moving testimonials
from clinical study participants have helped serve as a critical
element in the FDA's considerations of potentially the first
commercially available gene therapy for any type of hemophilia,"
said Hank Fuchs, M.D., President,
Global Research and Development at BioMarin. "As important,
we commend the EMA PRIME initiative for enabling enhanced
interactions and early dialogue that have optimized our development
plans and have helped speed up evaluation of this novel
investigational gene therapy."
ISTH Late-Breaking Abstract
Earlier today, Professor Pasi presented data in a late-breaking
abstract session on the efficacy and safety of valoctocogene
roxaparvovec in an ongoing Phase 1/2 study at the 27th
International Society on Thrombosis and Haemostasis (ISTH) 2019
Congress in Melbourne,
Australia.
The three-year update of the 6e13 vg/kg dose cohort in the Phase
1/2 study demonstrated that bleed rate control and reduction in
Factor VIII usage was maintained for a third year following a
single administration of valoctocogene roxaparvovec. In the
year prior to study entry, the mean Annualized Bleed Rate (ABR) was
16.3 and the median was 16.5. Over three years, the ABR was
reduced to a mean of 0.6 and a median of zero. This
represents a 96% reduction in participants' mean ABR, and there is
100% resolution of target joints. There was also a 96% reduction in
participants' mean annualized Factor VIII usage rate over three
years, and all participants remain off Factor VIII
prophylaxis. Factor VIII levels sustained over a three-year
period were sufficient to achieve striking hemostatic
efficacy. Factor VIII expression has entered a plateau phase
where the rate of decline has substantially slowed, which could be
indicative of durable, long-term expression.
"We are grateful to the study participants, who have made this
progress possible in less than four years since the first
participant was enrolled in a clinical study," Fuchs added.
"We have been moving efficiently through the development process,
in no small part because of our ability to treat clinical trial
participants with valoctocogene roxaparvovec produced using our
commercial process. Utilization of to-be-commercialized
material during Phase 3 studies significantly de-risks the program,
as no production or facility changes need to be made to support
commercial demand."
Valoctocogene Roxaparvovec Safety Summary
Overall, valoctocogene roxaparvovec continues to have a
favorable safety profile and has been well-tolerated by
participants across all doses in the Phase 1/2 and Phase 3
studies. No participants developed inhibitors to Factor VIII,
and no participants withdrew from the study. All participants
have remained off Factor VIII prophylaxis. Corticosteroid use was
transient with no long-lasting clinical sequelae. No
participants have developed thrombotic events. Transient
liver biomarker abnormalities and infusion-associated reactions
have been the primary treatment-related adverse events, with no
emergence of any delayed adverse events.
GENEr8-1 To Complete Enrollment in Early Fall 2019
While the planned regulatory submissions in 4Q 2019 will be
based on an interim analysis of the Phase 3 GENEr8-1 study results,
the trial will continue to enroll to its planned completion target
of 130 total patients. Completion of this portion of the
study is not required for initial marketing authorizations of
valoctocogene roxaparvovec. The final analysis from the Phase
3 GENEr8-1 study will be the basis for evaluating the clinical
superiority of valoctocogene roxaparvovec to prophylactic
Factor VIII replacement therapy. The completion of enrollment
of the GENEr8-1 study is expected in the early fall of 2019.
Regulatory Status
The FDA granted valoctocogene roxaparvovec Breakthrough Therapy
Designation based on preliminary clinical evidence indicating that
valoctocogene roxaparvovec may demonstrate substantial improvement
over available therapy. The FDA's Breakthrough Therapy
Designation program is intended to facilitate and expedite
development and review of new drugs to address unmet medical need
in the treatment of a serious condition. The EMA has granted
access to its Priority Medicines (PRIME) regulatory initiative for
valoctocogene roxaparvovec for its potential to benefit patients
with unmet medical needs based on early clinical data.
BioMarin's valoctocogene roxaparvovec has also 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.
Gene Therapy Manufacturing
BioMarin has constructed, commissioned, and validated one of the
first gene therapy manufacturing facilities of its kind in the
world, which is located in Novato, California. Marketing
authorization documentation will be included in the filings, and
the facility is ready for inspection to support approval.
This facility can support approximately 4,000 doses per year, and
the production process was developed in accordance with
International Conference on Harmonisation guidance for
Pharmaceuticals for Human Use, facilitating worldwide registration
with health authorities. In 2018, the International Society
for Pharmaceutical Engineering (ISPE) selected the Company's gene
therapy manufacturing facility as the Facility of the Year Category
Winner for Project Execution.
About Hemophilia A
People living with hemophilia A lack enough 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 severe hemophilia A often
experience painful, spontaneous bleeds into their muscles or
joints. Individuals with hemophilia A diagnosed as severe
make up 43 percent of the hemophilia A population. The
standard of care for severe hemophilia A is a prophylactic regimen
of replacement Factor VIII infusions administered intravenously up
to two to three times per week. Despite these regimens, many
people continue to experience 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 is born with 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 seven 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 Statement
This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc.(BioMarin),
including without limitation, statements about development of
BioMarin's valoctocogene roxaparvovec program generally; the
company's plans for regulatory submissions in the U.S, and
Europe in 4Q 2019, expectations
regarding the company's ongoing clinical trials, and the completion
of enrollment of the Phase 3 study. 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
the above interim data; additional data from the continuation of
the Phase 1/2 trial and the Phase 3 trial, any potential adverse
events observed in the continuing monitoring of the participants in
the clinical trials; the content and timing of decisions by the
U.S. Food and Drug Administration, the European Commission 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 valoctocogene
roxaparvovec for the clinical trials and commercially, if
approved; 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
BioMarin's Quarterly Report on Form 10-Q for the quarter ended
March 31, 2019, and future filings
and reports by BioMarin. 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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Traci
McCarty
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Debra
Charlesworth
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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.