BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) today announced interim
results from INSPIRE, a Phase 2 trial for reveglucosidase alfa, a
fusion protein of insulin-like growth factor 2 and acid
alpha-glucosidase (IGF2-GAA) being studied for the treatment of
late-onset Pompe disease (LOPD). The interim efficacy and safety
analysis is based on 24 patients who previously had been on
treatment with the enzyme replacement therapy, alglucosidase alfa,
and were switched to reveglucosidase alfa.
Investigators indicated that, while on treatment
with alglucosidase alfa, the majority of the patient population
were considered to have worsening of their Pompe disease over the
last 12 months. At week 24, the 18 patients on treatment with
reveglucosidase alfa and who completed the study demonstrated
respiratory muscle improvements with a mean increase of 2.2 points
from baseline in percent predicted Maximal Inspiratory Pressure
(MIP) and a mean increase of 3.1 points from baseline in percent
predicted Maximal Expiratory Pressure (MEP). Patients completing
the study also experienced a mean improvement of 26.1 meters in 6
Minute Walk Test (6MWT). In the 14 patients who met eligibility at
both screening and baseline and completed the study, a mean
increase of 3.8 points from baseline in percent predicted MIP also
was observed. The 18 patients completing the study showed a mean
decrease of 3.7 points from baseline in percent predicted Forced
Vital Capacity (FVC), but were considered relatively unchanged from
screening at -0.7 points in percent predicted. BioMarin will
present these data at an upcoming medical meeting.
"We are encouraged by the positive trends in
respiratory muscle strength as measured by pressures, which may
indicate a possible halt in decline or improvement in lung capacity
and endurance in late-onset Pompe disease,” said Hank Fuchs, M.D.,
Executive Vice President and Chief Medical Officer at BioMarin.
“Reveglucosidase alfa has the potential to be an additional choice
for Pompe patients, and we look forward to working with health
authorities and the patient community to advance this experimental
therapy to the next stage of clinical development.”
“Pompe is a progressive and debilitating disease,
and patients need additional treatment options. The reveglucosidase
alfa data appears promising and could be a potential new enzyme
replacement therapy that could make a meaningful difference to
late-onset Pompe patients,” said Professor Benedikt Schoser of the
Friederich-Baur Institute and speaker of the German working group
for Pompe disease.
TABLE 1: Reveglucosidase Alfa Interim Phase 2 Study
Results
Endpoint |
N |
Baseline (SD) |
Week 24 (SD) |
Mean change from baseline to week 24 (SD) |
MIP - mean % predicted |
18 |
50.0 (17.5) |
52.1 (15.9) |
2.2 (8.3) |
MEP - mean % predicted |
18 |
38.9 (12.3) |
42.0 (12.1) |
3.1 (8.7) |
6MWT - mean meters |
17 |
345.8 (95.3) |
371.9 (114.2) |
26.1 (40.6) |
FVCupright- mean % predicted |
18 |
60.7 (15.1) |
56.9 (14.2) |
-3.7 (4.4) |
Only patients with baseline and week 24 results are included
3.8% (6.4) absolute improvement per protocol analysis of MIP (14
patients who met eligibility at screening and baseline)
FVC change from screening -0.7%
TABLE 2: Reveglucosidase Alfa Interim Phase 2 Study
Baseline Characteristics
Baseline characteristic |
701-301(N=23)* |
Age – mean yrs (range) |
48.5 (19-69) |
Sex- M/F % |
48/52 |
Time on alglucosidase alfa – mean years (SD) |
5.5 (2.7) |
MIP – mean % predicted (SD) |
51.2 (17.2) |
MEP – mean % predicted (SD) |
40.9 (12.1) |
6MWT – mean meters (SD) |
317.7 (102.3) |
FVC Upright – mean % predicted (SD) |
60.7 (15.9) |
Use of walking aids in 6MWT- % |
34.8 |
Use of ventilatory support- % |
34.8 |
*One patient was excluded due to inclusion violation of not
being diagnosed with LOPD.
Safety
Six patients discontinued treatment early, and two patients
experienced serious adverse events. Hypoglycemia was
generally similar in frequency and severity as in the previous
study, and the overall pattern of safety was otherwise consistent
with experience using other enzyme replacement therapy.
INSPIRE Study Design
The INSPIRE clinical trial is a Phase 2 single-arm,
open-label, switchover study of reveglucosidase alfa in patients
with late-onset Pompe disease (LOPD) who have been receiving
treatment with recombinant human acid alpha glucosidase (rhGAA) for
48 weeks or longer. This study was changed from a Phase 2/3 to a
Phase 2 study to allow use of drug employing a new purification
process, which could be used in an anticipated Phase 3
registration-enabling trial. All patients in the study have been
transferred to the new material, and all future patients will be
treated with the new material.
Ambulatory patients who have mild to moderate respiratory
impairment will switch directly to receive reveglucosidase alfa 20
mg/kg by IV infusion every other week. The change in value in
primary endpoint, Maximum Inspiratory Pressure (MIP), and secondary
endpoint, Maximum Expiratory Pressure (MEP), Forced Vital Capacity
(FVC) Upright and Six-Minute Walk Test (6MWT) will be measured as
the difference between the Baseline value and the Week 24 value
within each individual subject. The study has a 24-week treatment
period followed by an extension period of up to 240 weeks.
About Reveglucosidase Alfa
Reveglucosidase alfa is an investigational enzyme replacement
therapy for Pompe disease. It is a novel fusion protein of
insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA)
designed to target delivery to the lysosomes where the enzyme is
most needed. The drug replaces the enzyme (GAA) that prevents the
glycogen build up that causes Pompe disease. It has a small protein
attached to it (IGF-2), which allows it to attach to the surface of
the muscle cell more tightly than the untagged enzyme (GAA).
Research has shown that reveglucosidase alfa is able to get into
the cell and clear much of the excess glycogen buildup that creates
the problems in Pompe disease.
About Pompe Disease
Pompe Disease is an autosomal recessive metabolic
disorder which damages muscle and nerve cells throughout the
body. It is caused by an accumulation of glycogen in the
lysosome due to deficiency of the lysosomal acid alpha-glucosidase
enzyme. The build-up of glycogen causes progressive muscle
weakness (myopathy) throughout the body and affects various body
tissues, particularly in the heart, skeletal muscles, liver and
nervous system. Measurement of maximal inspiratory and
expiratory pressures are used to assess pulmonary muscle function.
Maximal inspiratory pressure (MIP) is the maximal pressure that can
be produced by the patient trying to inhale through a blocked
mouthpiece. Maximal expiratory pressure (MEP) is the maximal
pressure measured during forced expiration through a blocked
mouthpiece after a full inhalation.
There are two main forms of Pompe disease: late
onset which occurs in about one in 57,000 births and infantile
onset which occurs in about one in 140,000 births. It is inherited
in an autosomal recessive manner, affects males and females
equally, and in most cases, both parents of an affected child are
asymptomatic carriers of the disease. The overall population is
believed to be 10,000 patients globally.
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 five commercialized products
and multiple clinical and pre-clinical product candidates. For
additional information, please visit www.BMRN.com.
Forward-Looking Statement
This press release contains forward-looking
statements about the business prospects of BioMarin Pharmaceutical
Inc., including, without limitation, statements about: the
development of reveglucosidase alfa; the continued clinical
development of reveglucosidase alfa; the final results of the Phase
2 trial of reveglucosidase alfa, and actions by regulatory
authorities. 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 reveglucosidase alfa;
the final analysis of the interim data; our ability to successfully
manufacture reveglucosidase alfa; the content and timing of
decisions by the U.S. Food and Drug Administration, the European
Commission and other regulatory authorities concerning
reveglucosidase alfa; and those factors detailed in BioMarin's
filings with the Securities and Exchange Commission, including,
without limitation, the factors contained under the caption "Risk
Factors" in BioMarin's 2014 Annual Report on Form 10-K, and the
factors contained in BioMarin's reports on Form 10-Q. Stockholders
are urged not to place undue reliance on forward-looking
statements, which speak only as of the date hereof. BioMarin is
under no obligation, and expressly disclaims any obligation to
update or alter any forward-looking statement, whether as a result
of new information, future events or otherwise.
BioMarin® is a registered trademark of BioMarin
Pharmaceutical Inc.
Contact:
Investors:
Traci McCarty
BioMarin Pharmaceutical Inc.
(415) 455-7558
Media:
Debra Charlesworth
BioMarin Pharmaceutical Inc.
(415) 455-7451
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