SAN RAFAEL, Calif.,
May 28, 2019 /PRNewswire/ -- BioMarin
Pharmaceutical Inc. (NASDAQ: BMRN) announced today that its
investigational gene therapy, valoctocogene roxaparvovec, for
adults with severe hemophilia A achieved pre-specified clinical
criteria for regulatory review in the U.S. and Europe. As of May
28, 2019, eight patients in the 20-patient cohort of the
Phase 3 GENEr8-1 study achieved Factor VIII levels of 40
international units per deciliter (IU/dL), or more, at 23 to 26
weeks, meeting the pre-specified criteria for Factor VIII activity
levels. The company will meet with the Food and Drug
Administration (FDA) and European Medicines Agency (EMA) to review
the phase 3 data and the other elements of a submission and intends
to announce the timing for its planned marketing applications in 3Q
2019.
Topline Data Results
As of the April 30, 2019 data
cutoff, between weeks 23 to 26, in a cohort of the Phase 3 GENEr8-1
study of valoctocogene roxaparvovec dosed at 6e13 vg/kg, seven of
16 study participants reached or exceeded the pre-specified Factor
VIII levels of 40 international units per deciliter using the
chromogenic substrate (CS) assay. Subsequent to the
April 30 cutoff, one additional
participant met that criteria, bringing the total to eight
participants.
For the 16 patients who had reached week 26 by the April 30 cutoff since administration
of valoctocogene roxaparvovec, the estimated median Annual
Bleed Rate (ABR) was zero and the estimated mean ABR was 1.5,
representing a reduction of 85% from baseline levels where all
patients were on standard of care prophylaxis. In addition,
there was an 84% reduction in median annualized Factor VIII usage
and a 94% reduction in mean FVIII usage annualized between week 5
and 26. In the 23 to 26 week time period the mean Factor VIII
level using the CS assay was 36 (SD=28) IU/dL and the median was 33
IU/dL.
"Reaching this pre-specified clinical endpoint is an important
milestone that brings us one step closer to a potential regulatory
submission in both the U.S. and Europe for valoctocogene roxaparvovec to treat
adults with severe hemophilia A," said Hank
Fuchs, M.D., President of Worldwide Research and Development
at BioMarin. "Our discussions with the FDA and EMA underscore
the high level of unmet need in the hemophilia community, and we
look forward to continuing our productive dialogue on the
submissions."
Regulatory Status
The U.S. Food and Drug Administration (FDA) granted
valoctocogene roxaparvovec Breakthrough Therapy
Designation. 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. To qualify for Breakthrough Therapy
Designation, preliminary clinical evidence must show that the drug
may demonstrate substantial improvement over existing
therapies.
The European Medicines Agency (EMA) has granted access to
its Priority Medicines (PRIME) regulatory initiative for
valoctocogene roxaparvovec. To be accepted for PRIME, an
investigational therapy has to show its potential to benefit
patients with unmet medical needs based on early clinical data.
PRIME focuses on medicines that may offer a major therapeutic
advantage over existing treatments, or benefit patients with no
treatment options. These medicines are considered priority
medicines within the European Union (EU).
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.
Conference Call and Webcast to be Held May 28, 2019 at 8:00 AM
Eastern Time
Interested parties may access a live video webcast that will
include audio and slides of the presentations via the investor
section of the BioMarin website. A replay of the meeting will
be archived on the site for one week.
For those who choose not to listen and view the event via
webcast, dial-in information for the audio portion of the webcast
can be accessed using:
U.S. / Canada Dial-in Number: (866) 502-9859
International Dial-in Number: (574) 990-1362
Conference ID: 2295086
Replay Dial-in Number: (855) 859-2056
Replay International Dial-in Number: (404) 537-3406
Conference ID: 2295086
Registrational Studies Underway; GENEr8-1 to Evaluate
Superiority
The global Phase 3 program includes two studies with
valoctocogene roxaparvovec, one with the 6e13 vg/kg dose (GENEr8-1)
and one with the 4e13 vg/kg dose (GENEr8-2). With the
goal of evaluating superiority of valoctocogene roxaparvovec to the
current standard of care, prophylactic therapy, the sample size of
the GENEr8-1 study is approximately 130 total participants.
The study is powered to evaluate superiority to the current
standard of care. Enrollment completion in the newly amended
GENEr8-1 study is expected in the third quarter of 2019.
GENEr8-2, the ongoing Phase 3 study with the 4e13 vg/kg dose,
remains unchanged with an N=40. The GENEr8-2 study is
expected to complete enrollment one to two quarters after GENEr8-1
in 2019.
BioMarin now has six clinical studies underway in its
comprehensive gene therapy program for the treatment of severe
hemophilia A. In addition to the two global Phase 3 studies
GENEr8-1 and GENEr8-2, the Company recently began a Phase 1/2 Study
with the 6E13kg/vg dose of valoctocogene roxaparvovec in
approximately 10 participants with pre-existing AAV5
antibodies. Two additional and separate studies, one to study
seroprevalence in people with severe hemophilia A and one
non-interventional study to determine baseline characteristics in
people with hemophilia A, are ongoing around the world.
Participants in the Phase 1/2 dose escalation study will continue
to be monitored as part of the global program underway.
Valoctocogene roxaparvovec investigational product from
BioMarin's commercial scale manufacturing facility will be used in
all BioMarin interventional studies going forward.
Product to support the additional participants in the GENEr8-1 has
been produced and is immediately available.
Valoctocogene Roxaparvovec Safety
Overall, valoctocogene roxaparvovec has been well-tolerated by
the 22 participants in the Phase 3 cohort at the 6e13 vg/kg
dose. No participants developed inhibitors to Factor VIII,
and no participants withdrew from the study. The most common
adverse events (AEs) were alanine aminotransferase (ALT) elevation
(17 participants, 77.3%), nausea (11 participants, 50%), headache
(10 participants, 45.5%), fatigue (9 participants, 40.9%),
arthralgia (8 participants, 36.4%), AST elevation (8 participants,
36.4%), nasopharyngitis (7 participants, 31.8%), back pain (6
participants, 27.3%), and oropharyngeal pain (5 participants,
22.7%). Three subjects experienced serious adverse events
(SAEs) (13.6%); two SAEs were related to infusion reactions, one
SAE of gastroenteritis was unrelated to treatment.
Gene Therapy Manufacturing
BioMarin has constructed one of the first gene therapy
manufacturing facilities of its kind in the world, which is located
in Novato, California. Good Manufacturing Practices (GMP)
production of valoctocogene roxaparvovec has commenced, and this
manufacturing facility will support pivotal clinical development
activities and anticipated commercial demand, if valoctocogene
roxaparvovec is approved. This facility is capable of supporting
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 FVIII protein to
help their blood clot and are at risk for painful, potentially
life-threatening bleeds from even modest injuries.
Additionally, people with severe hemophilia A often experience
painful, spontaneous bleeds into their muscles or joints. The
standard of care for the 43 percent of individuals with hemophilia
A who are severely affected is a prophylactic regimen of Factor
VIII infusions administered intravenously 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 (FVIII) 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 Statements
This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc., including
without limitation, statements about the development of BioMarin's
valoctocogene roxaparvovec program generally, the possibility of an
accelerated and/or conditional filing and approval by the FDA or
EMA, respectively; the impact of valoctocogene roxaparvovec gene
therapy for treating patients with severe hemophilia A, the
potential for valoctocogene roxaparvovec to reduce or eliminate
bleeds, reduce the number of Factor VIII infusions, improve the
quality of life and the ongoing clinical programs generally.
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
and additional 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 BioMarin's Annual and quarterly Reports on
Forms 10-K and 10-Q, 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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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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