SAN RAFAEL, Calif.,
March 20, 2021 /PRNewswire/
-- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced
that data from the open-label long-term extension of the Phase 3
study of 15 µg/kg dose of vosoritide was presented at an oral
presentation at ENDO21, the Endocrine Society's Annual Meeting
by Professor Ravi Savarirayan, M.B., B.S., M.D., clinical
investigator from the Murdoch Children's Research Institute, Royal
Children's Hospital, University of
Melbourne, Parkville, Victoria. Vosoritide is an investigational,
once daily injection analog of C-type Natriuretic Peptide (CNP) for
the treatment of achondroplasia, the most common form of
disproportionate short stature in humans.
The data from the open-label extension presented at ENDO21
showed that children maintained an increase in Annual Growth
Velocity (AGV) through the second year of continuous treatment with
vosoritide. Children who received two years of vosoritide
therapy had a baseline mean AGV of 4.28 cm/year. After one year of
treatment, mean AGV was 5.71 cm/year and after the second year mean
AGV was 5.65 cm/year, demonstrating sustained restoration of a
major portion of the growth deficit in achondroplasia through the
second year of treatment. Children also had an improved height
z-score, which is a measure of height relative to that of a similar
population of average height.
In the children who were crossed over from placebo to vosoritide
in the open-label extension arm, similar efficacy after one year
was observed compared to children who received treatment with
vosoritide after one year. Children who were crossed over to
treatment had a baseline mean AGV of 3.99 cm/year. After one
year of treatment, mean AGV was 5.57 cm per year.
Retention of subjects on treatment was high with 93% of patients
originally randomized to receive vosoritide remaining on treatment
two years later.
"This is an important extension of the original study's findings
and confirm that the benefits of vosoritide are sustained during
treatment through two years," said
Savarirayan. "While these two-year data are encouraging at
showing a durable treatment effect, longer term follow-up will
provide additional insights on improvements in body proportions and
whether such improvements can potentially make a difference in
certain aspects of a child's life."
"Maintaining a consistent level of growth is important because
it supports that vosoritide is addressing the root cause of
achondroplasia," said Melita Irving, Clinical Geneticist at Guy's and
St Thomas' NHS Foundation Trust, London,
UK and investigator for the vosoritide clinical program at
the Evelina London Children's Hospital. "The clinical program
for vosoritide is robust and will continue to evaluate the impact
on other important medical outcomes in achondroplasia through
long-term evaluation. Overall, the data are encouraging, and allows
us to imagine the potential for this first and only targeted
precision treatment for achondroplasia."
"We continue to take a relentless approach to advance our
understanding of how vosoritide could potentially benefit children
with achondroplasia, and to collect the information families and
physicians will need to make informed decisions about the choice of
treatment," said Hank Fuchs, M.D.,
President, Worldwide Research and Development at BioMarin. "We
are encouraged by the consistency of this data with our
expectations based on the known biology of CNP effects on growth,
and with earlier studies, specifically with regards to durability
of effect in absence of pathological advancement of bone
age. We are grateful to the children, families and
investigators for participating in this study and allowing the
opportunity for the scientific exchange of clinical data at medical
meetings like ENDO2021."
Vosoritide Safety
The 2-year data demonstrated that vosoritide, administered at
15ug/kg/day was generally well tolerated with no new safety
findings. The majority of adverse events (AEs) were mild and no
serious adverse events were reported as study drug-related.
Injection site reactions were the most common drug-related
AEs, and all were transient. There were no AEs related to
disproportionate bone growth or bone pathology. No clinically
significant blood pressure decreases or new safety findings were
observed.
Regulatory Status
In 2020, the European Medicines Agency (EMA) and U.S. Food and
Drug Administration (FDA) accepted and validated the marketing
authorization application for vosoritide for achondroplasia. The
Committee for Medicinal Products for Human Use (CHMP) opinion is
expected in Europe in June of
2021. The U.S. New Drug Application (NDA) for vosoritide is under
review by the FDA with a Prescription Drug User Fee Act (PDUFA)
target action date of August 20,
2021. In the United States, the Company has chosen to provide
the 2-year outcomes from the Phase 3 extension study to the FDA as
additional data to convey the vosoritide treatment effect and
long-term durability. The Company believes that supplying this
additional data could result in a major amendment, resetting the
current PDUFA target action date out three months to
November.
In January 2021, the Company
received notice from the FDA that the NDA for vosoritide had been
granted Priority Review Designation based on the serious pediatric
indication it addresses, and the lack of treatment options
currently available. Consistent with FDA's policy on changes to
review classification for an ongoing application review, the PDUFA
action date is not affected by this designation. If approved,
the vosoritide NDA may qualify for a Priority Review Voucher
(PRV). A PRV confers priority review to a subsequent drug
application that would not otherwise qualify for that designation.
The rare pediatric disease review voucher program is designed to
encourage development of new drugs and biologics for the prevention
or treatment of rare pediatric diseases.
Upon the acceptance of the regulatory submission for vosoritide,
the Agency reiterated a position raised during the Pediatric
Advisory Committee (PAC) and Endocrinologic and Metabolic Drugs
Advisory Committee (EMDAC) held on May 11,
2018 recommending two-year controlled trials in different
age groups. BioMarin believes the highly persuasive outcomes
from the one-year randomized, double-blind, placebo-controlled
Phase 3 trial, coupled with data from the Phase 2 program with up
to 5 years of long-term follow-up that has been compared to robust
natural history data on growth and the updated 2-year data from the
Phase 3 study, offers a rigorous and reliable method to assess
whether vosoritide has a durable impact on the rate of endochondral
bone growth that ultimately increases final adult height.
Vosoritide has also received orphan drug designation from the
FDA and EMA for the treatment of children with achondroplasia. 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.
Description of Phase 3 Extension Study
This is an ongoing open-label long-term extension study to a
completed pivotal, double-blind, placebo-controlled study of
vosoritide in children with achondroplasia. A total of 119 children
were enrolled in the extension study after completion of the
pre-treatment observation period and one year of treatment in the
pivotal phase 3 study, and all are receiving open-label treatment
with vosoritide 15 mcg/kg daily. Vosoritide is being tested in
children whose growth plates are still "open." This is
approximately 25% of people with achondroplasia. The extension
study is evaluating safety, AGV, and cumulative annual height gain
until participants reach final adult height. A wide range of
secondary and exploratory endpoints include anthropometric measures
such as height Z-score, body and limb proportionality and joint
geometry; biochemical, biomarker and radiological assessments of
bone growth and health; and evaluations of health-related quality
of life (HRQoL), developmental status, and functional
independence. These additional endpoints address the overall
impact vosoritide has on achondroplasia.
About Achondroplasia
Achondroplasia, the most common form of skeletal dysplasia
leading to disproportionate short stature in humans, is
characterized by slowing of endochondral ossification, which
results in disproportionate short stature and disordered
architecture in the long bones, spine, face and base of the
skull. This condition is caused by a change 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 the need for 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% of people with achondroplasia. In the
U.S., Europe, Latin America, the Middle East, and
most of Asia Pacific, there are currently no licensed
medicines for achondroplasia.
About BioMarin
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 such 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: the development of
BioMarin's vosoritide development program generally and
specifically about the results of the extension of the Phase 3
trial, the timing of actions by regulatory authorities including
the expectation of the CHMP opinion for vosoritide
in Europe in June of 2021; the potential for the
vosoritide NDA, if approved, to qualify for a Priority Review
Voucher; and the plan to submit the second year of Phase 3 data to
the FDA and the potential that this could result in a major
amendment, resetting the current PDUFA date out three months to
November. 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: final analysis of the extension of the Phase
3 data, results and timing of current and planned preclinical
studies and clinical trials of vosoritide; our ability to enroll
participants into such clinical trials, our ability to record data
during a global pandemic, our ability to successfully manufacture
vosoritide; the content and timing of decisions by the U.S. Food
and Drug Administration, the European Commission and other
regulatory authorities concerning vosoritide; and those other risks
and uncertainties detailed from time to time under the caption
"Risk Factors" and elsewhere in the BioMarin's Securities and
Exchange Commission (SEC) filings, including, without limitation
BioMarin's Annual Report on Form 10-K for the year ended
December 31, 2020, 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.
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