SAN RAFAEL, Calif.,
June 17, 2020 /PRNewswire/
-- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today
additional data from its previously reported four-year update of an
open-label Phase 1/2 study of valoctocogene roxaparvovec, an
investigational gene therapy treatment for severe hemophilia A. The
results were presented during a late-breaking oral presentation at
the World Federation of Hemophilia (WFH) Virtual Summit by
Professor John Pasi, M.B., Ch.B.,
Ph.D., from Barts and the London School of Medicine and Dentistry
and Chief Investigator for this Phase 1/2 study.
"With four years of data, this study represents the longest
duration of clinical experience for any gene therapy in hemophilia
A. It is exciting to observe that all study participants
remain off Factor VIII prophylaxis therapy, while also experiencing
a greater than 90 percent reduction in bleeding episodes from a
single administration of valoctocogene roxaparvovec," said
Professor Pasi. "These data demonstrate the very real
potential of a paradigm shift in the treatment of hemophilia A and
that ongoing research into gene therapies could represent an
entirely new way to approach meeting the high unmet need in
patients with severe hemophilia A."
"BioMarin is committed to the bleeding disorders community with
the most robust and advanced clinical development program for a
potential first gene therapy in severe hemophilia A," said
Hank Fuchs, M.D., President, Global
Research and Development at BioMarin. "We are pleased to
share these data at WFH. Demonstrating a 96% reduction in
exogenous Factor VIII usage as patients are now producing their own
endogenous factor VIII is a potential benefit that we hope to be
able to offer as we work closely with regulators to seek approval
and work to reduce the burden of hemophilia."
The data presented at WFH is the most current data (April 8, 2020, cut off) and includes four years
of data for the 6e13 vg/kg cohort and three years of data for the
4e13 vg/kg cohort.
Annualized Bleed Rate and Factor VIII Use in 6e13 vg/kg
Cohort
In the six study participants who were previously on Factor VIII
prophylaxis in the 6e13 vg/kg cohort, the data showed substantial
and sustained reductions in bleeding that required Factor VIII
infusions. In the year prior to treatment with valoctocogene
roxaparvovec, the mean Annualized Bleed Rate (ABR) was 16.3 and the
median was 16.5. During the four years following treatment with
valoctocogene roxaparvovec, the cumulative mean ABR was 0.8, which
represents a 95% reduction from baseline. In the fourth year, the
mean ABR was 1.3 and the median was zero (see Table 1). There was a
96% reduction in mean Factor VIII usage to 5.4 infusions per year
cumulatively over four years from the baseline of 135.6 infusions
per year.
Among all seven study participants in the 6e13 vg/kg cohort, 86%
or six out of seven were bleed-free in the fourth year. All
participants remain off Factor VIII prophylaxis therapy (see Table
1).
Annualized Bleed Rate and Factor VIII Use in 4e13 vg/kg
Cohort
Similarly, in the six study participants in the 4e13 vg/kg
cohort, the data showed substantial and sustained reductions in
bleeding requiring Factor VIII infusions following treatment with
valoctocogene roxaparvovec. All participants remain off Factor VIII
prophylaxis therapy.
In the year prior to treatment with valoctocogene roxaparvovec,
the mean ABR was 12.2 and the median was 8.0. The cumulative mean
ABR was reduced by 93% to 0.9 with continued absence of target
joint bleeds in 5 of 6 subjects during the three years observed,
which represents a 93% reduction from baseline. During the
third year of follow-up, the mean ABR was 0.5 and the median
was zero (0), and 67% or four out of six study participants were
bleed-free. Five out of six participants had no spontaneous bleeds.
There was a 96% reduction in mean Factor VIII usage to 5.7
infusions per year cumulatively over three years from the baseline
of 142.8 infusions per year. (see Table 1)
Factor VIII Activity Levels for 6e13 vg/kg and 4e13 vg/kg
Cohorts
For the 6e13 vg/kg and 4e13 vg/kg cohorts, mean Factor VIII
activity levels over four and three years, respectively, support
the observed reductions in bleed rates and annualized Factor VIII
usage. All study participants had severe hemophilia A at baseline,
defined as less than or equal to 1 IU/dL of Factor VIII
activity.
At the end of the fourth-year post-infusion with valoctocogene
roxaparvovec, all patients continue to produce their own endogenous
factor with the mean Factor VIII activity level of the 6e13 vg/kg
cohort at 24.2 IU/dL as measured by the chromogenic substrate (CS)
assay and at 35.4 IU/dL as measured by the One-Stage (OS)
assay. The median Factor VIII activity levels at the end of
the fourth year was 16.4 IU/dL as measured by the CS assay and 23.4
IU/dL as measured by the OS assay. These measurements are
based on six of the seven participants, as an evaluable sample for
the seventh study participant was not available.
Mean Factor VIII activity levels over three years similarly
support the observed reductions in bleed rates and annualized
Factor VIII usage for the 4e13 vg/kg cohort. At the end of
the third year post-infusion with valoctocogene roxaparvovec, mean
Factor VIII activity level of the 4e13 vg/kg cohort was 9.9 IU/dL
as measured by the CS assay and 14.9 IU/dL as measured by the OS
assay. The median Factor VIII activity levels at the end of
the third year was 7.9 IU/dL as measured by the CS assay and 12.3
IU/dL as measured by the OS assay (see Tables 2 and 3 for graphics
of data results).
Webinar with BioMarin and Study Investigators, Today at
5:00 PM ET
At 5pm ET, BioMarin management
will host a webinar with key clinical investigators, Professor
John Pasi and Dr. Steve Pipe, to discuss results from the Phase
1/2 Study of valoctocogene roxaparvovec gene therapy for severe
hemophilia A presented at the WFH Virtual Summit today.
Interested parties may access a live video webinar that will
include audio and slides at:
https://bmrn.zoom.us/j/94005113278
For access to the audio portion only, please use a dial-in
number in your region for the highest quality connection:
U.S. Dial-in Numbers: +1 669 900 6833 (Bay Area); +1
253 215 8782 (Washington); +1 346
248 7799 (Houston): +1 929 205
6099 (New York); +1 301 715 8592
(Maryland); +1 312 626 6799
(Chicago)
International Dial-in Numbers Available at:
https://bmrn.zoom.us/u/acdpx0wbxX
Webinar ID: 940 0511 3278
Safety Summary
Overall, the safety profile of valoctocogene roxaparvovec
remains consistent with previously reported data with no
delayed-onset, treatment-related events. No participants
developed inhibitors to Factor VIII, and no participants withdrew
from the study. No participants have developed thrombotic
events. The most common adverse events associated with
valoctocogene roxaparvovec occurred early and included transient
infusion-associated reactions and transient, asymptomatic, and mild
to moderate rise in the levels of certain proteins and enzymes
measured in liver function tests with no long-lasting clinical
sequelae.
Robust Clinical Program
The global Phase 3 study of valoctocogene roxaparvovec at the
6e13 vg/kg dose (GENEr8-1) evaluates superiority of valoctocogene
roxaparvovec to the current standard of care, FVIII prophylactic
therapy. The sample size of the GENEr8-1 study is
approximately 130 total participants. Enrollment is completed
and the data from this study is expected in the fourth quarter of
2020 or the first quarter of 2021.
BioMarin has five 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, 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. The Company is also running two
additional and separate studies, one to study AAV seroprevalence in
people with severe hemophilia A and one non-interventional study to
determine baseline characteristics in people with hemophilia
A. Participants in the Phase 1/2 dose escalation study will
continue to be monitored as part of the global program
underway.
Regulatory Status
The Food and Drug Administration (FDA) is reviewing the
biologics license application, under Priority Review, for
valoctocogene roxaparvovec with a PDUFA action date of August 21, 2020. The FDA also granted
valoctocogene roxaparvovec Breakthrough Therapy
designation.
The European Medicines Agency (EMA) validated the Company's
Marketing Authorization Application (MAA) for valoctocogene
roxaparvovec, which has been in review under accelerated assessment
since January. Recognizing valoctocogene roxaparvovec for its
potential to benefit patients with unmet medical needs, EMA granted
access to its Priority Medicines (PRIME) regulatory
initiative. Although the MAA remains under accelerated
assessment at this time, the Company expects the review procedure
to be extended by at least three months due to COVID-19
delays. Further, the Company believes there is a high
possibility that the MAA will revert to the standard review
procedure, as is the case with most filings that initially receive
accelerated assessment. Because of the combination of these
events, the Company expects an opinion from the Committee for
Medicinal Products for Human Use (CHMP) in late 2020/early
2021.
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.
The Company believes that both submissions represent the first
time a gene therapy product for any type of hemophilia indication
is under review for marketing authorization by health
authorities.
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: (i) the development of
BioMarin's valoctocogene roxaparvovec program generally, (ii) the
impact of valoctocogene roxaparvovec gene therapy for treating
patients with severe hemophilia A, (iii) the 4-year data
demonstrating the very real potential of a paradigm shift in the
treatment of hemophilia A and that ongoing research into gene
therapies could represent an entirely new way to approach meeting
the high unmet need in patients with severe hemophilia A, (iv) the
data from the Company's Phase 3 study expected in the fourth
quarter of 2020 or the first quarter of 2021, (v) that Factor VIII
activity levels over four years supporting reductions in bleed
rates and Factor VIII usage, and (vi) the potential approval and
commercialization of valoctocogene roxaparvovec for the treatment
of severe hemophilia A, including timing of such approval
decisions. 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; any potential adverse events observed in the
continuing monitoring of the patients in the Phase 1/2 trial; the
content and timing of decisions by the FDA, the European Commission
and other regulatory authorities, including the potential impact of
the COVID-19 pandemic on the regulatory authorities' abilities to
issue such decisions and the timing of such decisions; the content
and timing of decisions by local and central ethics committees
regarding the clinical trials; BioMarin's ability to successfully
manufacture valoctocogene roxaparvovec; 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, 2020, 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:
|
|
Investors
|
Media
|
Traci
McCarty
|
Debra
Charlesworth
|
BioMarin
Pharmaceutical Inc.
|
BioMarin
Pharmaceutical Inc.
|
(415)
455-7558
|
(415)
455-7451
|
View original content to download
multimedia:http://www.prnewswire.com/news-releases/biomarin-provides-additional-data-from-recent-4-year-update-of-ongoing-phase-12-study-of-valoctocogene-roxaparvovec-gene-therapy-for-severe-hemophilia-a-in-late-breaking-oral-presentation-at-world-federation-of-hemophilia-virtual-301078398.html
SOURCE BioMarin Pharmaceutical Inc.