UK Regulatory Agency Approves Continued Enrollment in BioMarin Phase 1/2 Study of BMN 270 in Hemophilia A
October 13 2016 - 4:01PM
Phase 1/2 Study Expected to Resume by End of
2016
BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) announced today that the
Medicines and Healthcare Products Regulatory Agency (MHRA) in the
United Kingdom approved continued enrollment into the open-label
Phase 1/2 study of BMN 270, an investigational gene therapy
treatment for severe hemophilia A. BioMarin had previously
announced that after enrolling the first 9 patients in the study,
that dosing of patients had been suspended due to observed
increases in alanine aminotransferase (ALT) levels that exceeded a
pre specified threshold set by the company. Following study
suspension, the company reviewed safety and efficacy data on the 9
patients with the MHRA, and based on its review, the MHRA approved
resumption of the study. The agency also approved the company’s
proposed amendments to the study, which included eliminating the
requirement for prophylactic corticosteroids and increasing
potential additional enrollment from up to three additional
patients to up to six additional patients.
BioMarin intends to resume enrollment in the Phase I/2 study
before the end of 2016. Based on protocol amendments, three
patients will be enrolled at a dose of 4 x 1013 vg/kg, and an
additional three may be enrolled at this dose or the previously
tested high dose of 6 x 1013 vg/kg. In the up to six
additional patients, the requirement for prophylactic
corticosteroids has been removed and the threshold for starting
therapeutic corticosteroids has been increased. Safety and
efficacy data from these patients will inform the Phase 2b study
planned to begin in the second half of 2017.
“We are pleased that MHRA has approved the resumption of
enrollment of the BMN 270 study, as well as the study
amendments. We believe that the amendments will allow us to
optimize the design of a robust Phase 2b clinical trial, which
potentially could support an accelerated approval by health
authorities,” said Hank Fuchs, M.D., Chief Medical Officer at
BioMarin. “We are grateful to the patients who are
participating in this current study, and are encouraged by the
results so far for this Phase 1/2 trial.”
Phase 1/2 Study Design
The current Phase 1/2 study is evaluating the safety and
efficacy of BMN 270 gene therapy in up to 15 patients with severe
hemophilia A defined by the WFH as less than 1% of blood clotting
factor. The primary endpoints are to assess the safety of a single
intravenous administration of a recombinant AAV vector coding for
human-coagulation factor VIII and to determine the change from
baseline of factor VIII expression level at 16 weeks after
infusion. The kinetics, duration and magnitude of AAV-mediated
factor VIII activity in individuals with hemophilia A will be
determined and correlated to an appropriate BMN 270 dose.
This is a dose escalation study with the goal of observing an
increase in factor VIII levels. Secondary endpoints include
assessing the impact of BMN 270 on the frequency of factor VIII
replacement therapy, the number of bleeding episodes requiring
treatment and any potential immune responses. Patients will be
monitored for safety and durability of effect for five years.
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.1 As an X-linked disorder, hemophilia A mostly
affects males, occurring in approximately 1 in 5,000 male
births.2 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.3 Even with prophylactic
regimens, many patients still experience microbleeds and
spontaneous bleeding events that result in progressive joint
damage.
About Gene Therapy
Gene therapy is a treatment designed to alter a genetic problem
by adding a corrected copy of the defective gene. The functional
gene is inserted into a vector – containing a DNA sequence coding
for a specific protein – that acts as a delivery mechanism,
providing the ability to deliver the functional gene to cells. The
cells can then use the information to build the functional protein
that the body needs, potentially reducing or eliminating the cause
of the disease. Currently, gene therapy for the treatment of
hemophilia A is available only as part of a clinical trial.
The AAV approach to gene therapy has been advanced at the
University College London (UCL) in the treatment of Hemophilia B.
At UCL, this technology has shown evidence to be both safe
and effective, correcting bleeding for greater than four years in a
continuing clinical trial.
About BioMarin
BioMarin is a global biotechnology company that develops and
commercializes innovative therapies for people with serious and
life-threatening rare disorders. 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.
Information on BioMarin's 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 the
development of BioMarin's BMN 270 program generally and the timing
and results of the Phase 1/2 clinical trial and anticipated Phase
2b trial of BMN 270. 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 BMN
270, 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 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 the
product candidate for the preclinical and clinical trials; 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 2015
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.
_________________________________________1 Source: National
Hemophilia
Foundation http://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A 2 Source:
CDC
http://www.cdc.gov/ncbddd/hemophilia/data.html 3 Source:
World Federation of Hemophilia
http://www.wfh.org/en/resources/annual-global-survey http://www.wfh.org/en/abd/prophylaxis/prophylaxis-administration-and-dosing-schedules
Contact:
Investors:
Traci McCarty
BioMarin Pharmaceutical Inc.
(415) 455-7558
Media:
Debra Charlesworth
BioMarin Pharmaceutical Inc.
(415) 455-7451
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