SAN RAFAEL, Calif.,
Oct. 18, 2017 /PRNewswire/ --
BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) updated the investment
community on the Company's development portfolio, which is focused
on innovative therapies to treat rare and ultra-rare diseases.
"We are pleased to share the progress of our development
programs in therapies to treat rare genetic diseases; hemophilia A,
PKU, achondroplasia and our next IND into Friedreich's Ataxia,"
said Hank Fuchs, M.D., President
Worldwide Research and Development of BioMarin. "In the near
term, we are expecting an FDA decision on pegvaliase to treat
adults with uncontrolled PKU in the first half of next year, and we
continue to be rapidly and decisively developing the potential
first gene therapy for severe hemophilia A."
BioMarin Selects BMN 290 for Friedreich's Ataxia
BioMarin announced today that it has selected BMN 290, a
selective chromatin modulation therapy, for the treatment of
Friedreich's Ataxia (FA). FA is a rare autosomal recessive
disorder with worldwide prevalence of approximately 15,000, which
results in disabling neurologic and cardiac progressive
decline. Currently there are no approved disease modifying
therapies for FA. In preclinical models, BMN 290 increases
frataxin expression in affected tissues more than two-fold.
BMN 290 is a second generation compound derived from a compound
acquired from Repligen that had human clinical data demonstrating
increases in frataxin in FA patients. BMN 290 was selected
for its favorable penetration into the central nervous system and
cardiac target tissues, and its preservation of the selectivity of
the original Repligen compound. The company expects to submit
the IND in 2H 2018.
BMN 270 Gene Therapy for Severe Hemophilia A
BioMarin announced today that the FDA has completed their review
of the IND application for BMN 270, an investigational gene therapy
treatment for severe hemophilia A, and concluded that it can
proceed. The IND application included 52-week data at the
6e13 vg/kg dose and the protocol for the Phase 3 study using the
6e13 vg/kg dose. The protocol for the second Phase 3 study
using the 4e13 vg/kg dose has also been submitted to the
FDA.
BioMarin also announced today that the Phase 3 Clinical Trial
Application was approved by the UK Medicines and Healthcare
Products Regulatory Agency (MHRA).
The company expects to initiate the global Phase 3 program in
the fourth quarter of 2017.
Data Update on Phase 1/2 Study of 4e13 vg/kg Dose
In addition, the company provided an update on the ongoing
open-label Phase 1/2 study of the 4e13 vg/kg dose at up to 36 weeks
of observation at the September 14,
2017 data cut. Since the last data update provided
during the Q2 earnings call on August 2,
2017, five of the six patients at the 4e13 vg/kg dose
tracked to the low range of normal, and the sixth is in the mild
range for Factor VIII levels. Median annualized bleed and
factor VIII use rates for 4e13 and 6e13 vg/kg were zero after Week
4.
Factor VIII Levels
(%) of 4e13 vg/kg Dose Patients* by Visit (N=6)
|
|
Week**
|
4
|
8
|
12
|
16
|
20
|
24
|
28
|
32
|
36
|
4e13 vg/kg
Dose
|
|
|
|
|
|
|
|
|
|
n
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
3
|
3
|
Median
Factor VIII
Level*** (%)
|
4
|
15
|
21
|
29
|
34
|
28
|
31
|
51
|
45
|
Mean
Factor VIII
Level*** (%)
|
5
|
13
|
19
|
26
|
31
|
29
|
30
|
51
|
47
|
Range
(low, high)
|
(2,10)
|
(3,21)
|
(6,32)
|
(5,38)
|
(7,45)
|
(7,43)
|
(4,44)
|
(48,54)
|
(41,55)
|
|
*All patients had
severe hemophilia A, defined as less than or equal to 1% of Factor
VIII activity levels, expressed as a percentage of normal factor
activity in blood.
|
**Weeks were
windowed by +/- 2 weeks
|
*** Bolded numbers
are in the mild to normal range of Factor VIII activity as defined
by the World Federation of Hemophilia,
http://www.wfh.org/en/page.aspx?pid=643 (link current as
of Oct. 17, 2017). Factor VIII levels are determined by one-stage
assay.
|
BMN 270 Reduces
Bleeds and Factor VIII Use: Summary of Mean Annualized
Bleeding Rate (ABR) and FVIII Use Rate of 4e13 vg/kg Dose for
Patients Previously on Prophylaxis (N=6) at September 14, 2017 data
cut
|
|
|
Before BMN 270
Infusion
|
After BMN 270
Infusion
|
|
Median (mean,
SD)
|
Median (mean,
SD)
|
Annualized
Bleeding Rate*
(bleeding episodes per
year per subject)
|
8.0 (12.2,
15.4)
|
0.0 (0.8,
1.9)
|
Annualized FVIII
Use Rate*
(infusions per year per
subject)
|
155.5 (146.5,
41.6)
|
0.0 (2.7,
6.7)
|
|
*Post-infusion
data were based on data after Week 4
|
BMN 270 Generic Name is Valoctocogene Roxaparvovec
BioMarin was issued the International Nonproprietary Name (INN)
valoctocogene roxaparvovec for BMN 270. The World Health
Organization (WHO) has approved the INN "valoctocogene
roxaparvovec" for the Company's gene therapy to treat hemophilia
A. International Nonproprietary Names (INN) identify
pharmaceutical substances or active pharmaceutical ingredients.
Each INN is a unique name that is globally recognized and is public
property. A nonproprietary name is also known as a generic
name.
Gene Therapy Manufacturing
BioMarin has constructed one of the largest gene therapy
manufacturing facilities in the world, which is located in
Novato, California. Good
Manufacturing Practices (GMP) production of BMN 270 has commenced
and will support clinical development activities and anticipated
commercial demand. This facility is capable of supporting
approximately 2,000 patients 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.
Vosoritide Data Update
BioMarin provided an update on its open-label Phase 2 study of
vosoritide, an analog of C-type Natriuretic Peptide (CNP), in
children with achondroplasia, the most common form of
disproportionate short stature in humans.
Vosoritide for achondroplasia demonstrates sustained increase in
average growth velocity over 30 months of treatment in 10 children,
who completed 30 months of daily dosing at 15 µg/kg/day. Over
this period of time, patients have experienced mean absolute growth
increase of approximately 4 cm over what their baseline growth
velocity would have predicted.
The sustained increase in annualized growth velocity was
accompanied by sustained improvements over time in height compared
to age- and gender-matched unaffected children as measure by
z-scores. In addition, treatment with vosoritide shows
continued improvement over time in proportionality as measured by a
ratio of the upper and lower body measurements or U/L
ratio.
Pegvaliase Program Update
The Pegvaliase Biologics License Application (BLA) remains on
Track for FDA Action during the first half of 2018. The
company plans to submit a Marketing Authorization Application (MAA)
to the European Medicines Agency (EMA) in Q1 2018.
2017 Full-year Total Revenue and Non-GAAP Guidance
reaffirmed
Today, the Company commented on their Total Product Revenue and
Non-GAAP trends for the third quarter and full-year 2017. In
terms of the overall commercial business, BioMarin stated that
sales of products in markets throughout most of the world are
performing at or above internal expectations. However, the
Company said the one exception is Brazil, where a slowdown in Federal purchasing
orders has extended into the third quarter of this year. As a
result, third quarter revenues are expected to be negatively
impacted. For the fourth quarter, if orders are placed in
Brazil as expected, Total Product
Revenue for full-year 2017 is anticipated to be in the mid-point of
guidance. However, if sales to Brazil continue to be slow in the fourth
quarter, full-year 2017 Total Product Revenue may be at the low end
of guidance. Regardless of Brazilian ordering patterns for
the remainder of the year, and based on careful expense control,
the Company still expects to be in the mid to high-end of Non-GAAP
profitability guidance for full-year 2017.
About BioMarin and Disease Information
BioMarin is a global biotechnology company that develops and
commercializes innovative therapies for patients with 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.
About Friedreich's Ataxia
Friedreich's ataxia (FA) is a progressive, neurological disorder
that affects approximately 15,000 people in the United States and Europe, typically resulting in wheelchair
dependence in young adulthood and early death due to cardiac
failure. It is caused by mutations in the FXN gene, and is
inherited in an autosomal recessive manner. FXN mutations result in
reduced expression of frataxin protein, manifesting in progressive
neurological and cardiac damage. Major neurological symptoms
include muscle weakness and ataxia, a loss of balance and
coordination. These symptoms typically appear between 10 and 15
years of age, but FA has been diagnosed in people from ages 2 to 50
with earlier onset associated with a more severe course.
BMN 270 Safety
Overall, BMN 270 has been well-tolerated by patients across all
doses, including the two patients that received the lowest doses of
6e12 and 2e13 vg/kg, respectively. No patients developed
inhibitors to Factor VIII and no patients withdrew from the
study. The most common adverse events (AEs) across all dose
cohorts were alanine aminotransferase (ALT) elevation (11 patients,
73%); arthralgia, aspartate aminotransferase elevation, and
headache (7 patients each, 47%); back pain and fatigue (5 patients
each, 33%). Two patients reported Serious Adverse Events
(SAEs) during the study. One patient was hospitalized for
observation after developing Grade 2 pyrexia with myalgia and
headache within 24 hours of receiving BMN 270. The event
resolved within 48 hours following treatment with paracetamol, an
over-the-counter treatment for pain and fever. The event was
assessed as related to BMN 270. The other SAE was assessed as
not related to BMN 270, attributed to a planned knee surgery to
treat hemophilic arthropathy, and Grade 1 in severity. No
complications were reported.
About Hemophilia A
Hemophilia A, also called Factor VIII (FVIII) deficiency or
classic hemophilia, is a 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. As an
X-linked disorder, hemophilia A mostly affects males, occurring in
approximately 1 in 5,000 male births. People living with the
disease are not able to form blood clots efficiently and are at
risk for excessive bleeding from modest injuries, potentially
endangering their life. People with severe hemophilia often bleed
spontaneously into their muscles or joints. The standard of care
for the 43% of hemophilia A patients who are severely affected, is
a prophylactic regimen of Factor VIII infusions three times per
week. Even with prophylactic regimens, many patients still
experience microbleeds and spontaneous bleeding events that result
in progressive joint damage.
Vosoritide Safety
Vosoritide was generally well tolerated at all doses. The
majority of adverse events (AEs) were mild and no serious AEs were
reported as study drug-related. Across all doses, injection site
reactions and hypotension were the most common drug-related AEs.
All injection site reaction events were transient. AEs of
hypotension were mild, transient and resolved without medical
intervention, and the majority were asymptomatic and reported in
context of routine blood pressure measurements. No new safety
findings were observed at the 30 µg/kg/day dose.
About Achondroplasia
Achondroplasia, the most common form of disproportionate short
stature in humans, is characterized by failure of normal conversion
of cartilage into bone, which results in disproportionate short
stature. This condition is caused by a mutation in the
fibroblast growth factor receptor 3 gene (FGFR3), a negative
regulator of bone growth. Beyond disproportionate short stature,
people with achondroplasia can experience serious health
complications, including foramen magnum compression, sleep apnea,
bowed legs, mid-face hypoplasia, permanent sway of the lower back,
spinal stenosis and recurrent ear infections. Some of these
complications can result in invasive surgeries such as spinal cord
decompression and straightening of bowed legs. In addition, studies
show increased mortality at every age.
More than 80% of children with achondroplasia have parents of
average stature and have the condition as the result of a
spontaneous gene mutation. The worldwide incidence rate of
achondroplasia is about one in 25,000 live births. Vosoritide
is being tested in children whose growth plates are still "open,"
typically those under 18 years of age. This is approximately
25 percent of people with achondroplasia. In the United States, Europe, Latin
America and the Middle
East, there is currently no licensed medicines for
achondroplasia.
Pegvaliase Safety
The safety data set for all pegvaliase trials includes exposure
up to seven years and approximately 680 patient years of treatment,
300 of which are from the Phase 3 program. Most Adverse
Events (AEs) were mild or moderate in severity. 8.5% of
patients reported AEs leading to study withdrawal. The most
common Adverse Events (AEs) were arthralgia (69.5%), injection site
reaction (65.1%), headache (51.9%), nasopharyngitis (41.1%), and
rash (40.2%).
Pegvaliase treated patients had acute systemic hypersensitivity
adverse events (4.6%) as defined by the broad National Institute of
Allergy and Infectious Disease and the Food Allergy and Anaphylaxis
Network (NIAID/FAAN) (Sampson's) criteria for anaphylaxis by expert
external adjudication. Hypersensitivity adverse events and
acute systemic hypersensitivity events mainly occurred in the first
year of treatment. With prolonged exposure, AE rates declined
for almost all categories. Using high-sensitivity assays,
anti-drug IgE was undetected in the observed acute systemic
hypersensitivity events. Eight of the 13 patients with acute
systemic hypersensitivity events were re-dosed and six of the eight
re-dosed patients continued therapy.
About Phenylketonuria
Phenylketonuria (PKU) is a genetic disorder affecting
approximately 50,000 diagnosed patients in the developed world and
is caused by a deficiency of the enzyme PAH. This enzyme is
required for the metabolism of Phe, an essential amino acid found
in most protein-containing foods. If the active enzyme is not
present in sufficient quantities, Phe accumulates to abnormally
high levels in the blood and becomes toxic to the brain, resulting
in a variety of complications including severe intellectual
disability, seizures, tremors, behavioral problems and psychiatric
symptoms. As a result of newborn screening efforts implemented in
the 1960s and early 1970s, virtually all individuals with PKU or
PAH deficiency under the age of 40 in developed countries are
diagnosed at birth and treatment is implemented soon after. PAH
deficiency can be managed with a Phe-restricted diet, which is
supplemented by low-protein modified foods and Phe-free medical
foods; however, the strict diet is difficult for most adult
patients to adhere to the extent needed for achieving adequate
control of blood Phe levels. To learn more about PKU and PAH
deficiency, please visit www.PKU.com. Information on this
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., including,
without limitation, statements about its development programs and
regulatory actions related to these programs, including the
expected timing of the filing of the MAA for pegvaliase and an FDA
decision on pegvaliase, the timing of its anticipated submission of
an IND for BMN 290, BioMarin's BMN 270 program generally, the
timing of the initiation of the global Phase 3 program, the
expected design and size of the Phase 3 studies and a Phase 1/2
study in subjects with pre-existing antibodies against AAV5,
expected regulatory actions related to BMN 270, the expectations of
total BioMarin revenues for the third quarter and full year 2017
and the financial performance of BioMarin as a whole, and
statements about the anticipated capacity of the Company's gene
therapy manufacturing facility. 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 our product candidates, the continued clinical
experiences of the patients in the current clinical studies; 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 our product candidates for the
preclinical and clinical trials; the ordering patterns for our
commercial products, particularly orders from Brazilian
governmental entities; 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
June 30, 2017, 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 trademarks of BioMarin Pharmaceutical
Inc.
Contacts:
|
|
Investors
|
Media
|
Traci
McCarty
|
Debra
Charlesworth
|
BioMarin
Pharmaceutical Inc.
|
BioMarin
Pharmaceutical Inc.
|
(415)
455-7558
|
(415)
455-7451
|
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