6 of 7 High Dose Patients Show Factor VIII levels
above 50%, 7th patient above 10%
BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) announced today positive
interim results of an open-label Phase 1/2 study of BMN 270, an
investigational gene therapy treatment for severe hemophilia A at
the XXXII International Congress of the World Federation of
Hemophilia (WFH). The data was presented in the Late Breaking
Gene Therapy session by John Pasi, Professor of Haemostasis and
Thrombosis, Barts and the London School of Medicine, Honorary
Consultant Haematologist, The Royal London Hospital, and a lead
investigator of the study. The data presented at the congress
is an update since the Company reported initial results on this
same study on April 20, 2016. To access the data presented at
the Congress, click here.
A total of nine patients with severe hemophilia A received a
single dose of BMN 270, seven of whom have been treated at the
highest dose of 6 x 1013 vg/kg. As of the July 6 data cut
off, post-treatment follow-up ranges from 12 to 28
weeks. For the seven patients treated with the high dose, as
of each patients’ most recent reading, six of seven patients had
Factor VIII levels above 50%, as a percentage calculated based on
the numbers of International Units per deciliter of plasma (IU/dL),
and the seventh was above 10%. In addition, four patients who
have been followed the longest had a mean Factor VIII level of 146%
at their 20 week visit. Two patients with Factor VIII levels
above 200% had no unexpected events or need for medical
intervention. For the seven patients at the high dose, the median
annualized bleeding rate measured from day of gene transfer to data
cut of observation period fell to 5 from 20.
No clinically relevant sustained rises in ALT levels or other
markers of liver toxicity have been observed. The maximum ALT
levels were between 23 and 82 U/L (less than two times the upper
limit of normal, which is 43 U/L for the central laboratory in this
study) approximately 12 weeks after gene delivery and generally
declined over the next few weeks. ALT rises have not been
associated with any decrease in Factor VIII levels. A steroid
regimen administered to all high dose patients has been
well-tolerated. Patients are successfully tapering off of
steroids with two subjects off steroid therapy for up to 2.5 weeks
with no adverse impact on Factor VIII expression or ALT
levels. Study medication was generally well tolerated.
No serious adverse events were observed, and most common adverse
events were mild in severity.
“These data provide strong proof of concept evidence that
restoration of clotting function may be achieved by gene therapy,”
said John Pasi, Ph.D. F.R.C.P, Professor of Haemostasis and
Thrombosis at Barts and the London School of Medicine and Dentistry
and primary investigator for the BMN 270 Phase 1/2 clinical
trial. “For the first time, patients have reason to hope to
avoid bleeding and the opportunity to live a normal life.”
“We look forward to collaborating with experts and health
authorities to design the next phase of investigation,” said Hank
Fuchs, M.D., Chief Medical Officer at BioMarin. “Beginning in
mid-2017, a Phase 2b study will seek to evaluate the optimal dose
of BMN 270 using Factor VIII expression as the primary endpoint
with material from the to-be-commercialized manufacturing
process. If successful, this study could support an
accelerated approval given the severe unmet need, the substantial
effect and tolerability of the treatment.”
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 12 patients with severe
hemophilia A, as 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.
Conference Call with Slides to be Held Wednesday, July
27th at 4:05 pm ET
Interested parties may access a live webcast and slide
presentation that will accompany the conference call by going here
or accessing the investor section of the BioMarin
website, www.biomarin.com. A slide presentation will
accompany the conference call and can be seen using the webcast
link. Separately, the Late Breaker slide presentation will be
available to download in advance of the call. A replay of the
call will be archived on the site for one week following the
call.
U.S. / Canada Dial-in Number: (866) 502-9859 International
Dial-in Number: (574) 990-1362 Conference ID: 52603053
Replay Dial-in Number: (855) 859-2056 Replay International
Dial-in Number: (404) 537-3406 Conference ID: 52603053
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 clinical 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; 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
Foundationhttp://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A
2 Source:
CDChttp://www.cdc.gov/ncbddd/hemophilia/data.html
3 Source: World Federation of
Hemophiliahttp://www.wfh.org/en/resources/annual-global-surveyhttp://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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