Shire Reports Positive Results From First of Three Phase III Trials of velaglucerase alfa for Type 1 Gaucher Disease and Provides Important Updates on Interactions With FDA
Treatment Protocol Accepted and Rolling Submission of New Drug Application Initiated
LEXINGTON, Massachusetts, August 3/PRNewswire-FirstCall/ --
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today reported positive results from the
first of three Phase III studies of velaglucerase alfa, its enzyme
replacement therapy in development for the treatment of Type 1
Gaucher disease. The Company also announced that the U.S. Food and
Drug Administration (FDA) has accepted its treatment protocol for
velaglucerase alfa and that Shire has begun its rolling submission
of the New Drug Application (NDA) for velaglucerase alfa allowed
under the Fast Track process.
"We are very pleased with the progress of the velaglucerase alfa
program from both a clinical and regulatory perspective," said
Sylvie Gregoire, President of Shire Human Genetic Therapies. "This
data are consistent with those previously reported from the Phase
I/II and extension studies. We will continue to work diligently
with the FDA and other regulatory agencies to make velaglucerase
alfa available as soon as possible to help meet the needs of the
Gaucher community."
Shire's velaglucerase alfa program is the largest and most
comprehensive set of Phase III clinical trials conducted to date
for Gaucher disease. Over 100 patients at 24 sites in 10 countries
around the world have participated in the clinical studies.
Velaglucerase alfa is made using Shire's proprietary technology,
in a human cell line. The enzyme produced has the exact human amino
acid sequence and carries a human glycosylation pattern.
Phase III Study Overview and Results
The first trial in the Phase III program to be completed was a
multicenter, randomized, double-blind, two dose study of
velaglucerase alfa in patients with Type 1 Gaucher disease. The
primary goal of this study was to evaluate the safety and efficacy
of velaglucerase alfa in 25 patients with Type 1 Gaucher
disease.
Patients aged two years and older who were treatment naive were
eligible to participate in the study if they presented with
disease-related anemia and had at least one of the following
clinical manifestations of Gaucher disease: thrombocytopenia,
moderate splenomegaly or a readily palpable enlarged liver.
Patients were randomized to receive velaglucerase alfa at either 45
U/ kg or 60 U/ kg for a duration of 12 months.
In the trial, the primary endpoint was reached with patients
benefiting from a clinically important and statistically
significant (p<0.0001) increase in mean hemoglobin concentration
compared with baseline after receiving velaglucerase alfa at 60
U/kg IV every other week for 12 months. Statistically significant
improvements compared with baselines were also observed in platelet
and spleen sizes, and nominally significant improvements were
observed in liver size at this dose. Results were clinically
important as defined by standard criteria and consistent with the
previously published Phase I/II data.
At the 45 U/kg IV dose, statistically significant improvements
in hemoglobin, platelet count, and spleen volume were also
demonstrated. The magnitude of changes in the 45U/kg dose was also
clinically important, and a trend in liver volume reduction was
observed. The 60U/kg dose performed numerically as well or better
than 45U/kg across all measured clinical endpoints.
The specific data from this trial will be presented at a
scientific meeting later this year.
Velaglucerase alfa was found to be generally well tolerated with
no drug-related serious adverse events reported in the trial. No
patients withdrew from the trial due to an adverse event.
Most of the drug-related adverse events were reported in
association with velaglucerase alfa infusions, all of which were
mild and resolved without sequelae.
"These findings are very encouraging. They illustrate important
potential benefits that velaglucerase alfa may provide to patients
who are affected by Type 1 Gaucher disease," said Dr. Atul Mehta,
Clinical Director of the Lysosomal Storage Disorders Unit, Royal
Free Hospital, London. "Velaglucerase alfa appears to be an
excellent choice for Type 1 Gaucher patients. The prospect of
having another treatment option available to help patients achieve
therapeutic goals is very important and is welcomed by both the
physicians and patients."
Regulatory Updates
With regard to ongoing interactions with the FDA, Shire provided
the following important updates:
- The FDA has accepted Shire's treatment protocol for velaglucerase alfa.
The acceptance of the treatment protocol by the FDA will enable
physicians to treat Gaucher patients with velaglucerase alfa prior to
commercialization. Shire will initially provide velaglucerase alfa free
of charge to patients who are enrolled in the protocol.
- Shire has begun a rolling submission of a New Drug Application (NDA) to
the FDA for velaglucerase alfa to treat patients with Type 1 Gaucher
disease. The submission was initiated on July 30, 2009, three weeks
after Shire received Fast Track designation. Fast Track designation
allows a company to file the sections of the NDA as they become available
and enables the agency to commence its review on a rolling basis. The
company expects to complete the NDA submission by the end of this
quarter.
Background on Gaucher disease
Gaucher disease is an autosomal recessive disease and the most
prevalent Lysosomal Storage Disorder (LSD), with an incidence of
about 1 in 20,000 live births. Despite the fact that Gaucher
Disease consists of a phenotype, with varying degrees of severity,
it has been sub-divided in three subtypes according to the presence
or absence of neurological involvement. It is also the most common
genetic disease affecting Ashkenazi Jewish people (Eastern, Central
and Northern European ancestry), with a carrier frequency of 1 in
10 (Dr. John Barranger and Dr. Ed Ginns 1989). This panethnic
disease involves many organ systems, such as liver, spleen, lungs,
brain, metabolism and bone marrow.
Gaucher Disease results from a specific enzyme deficiency in the
body, caused by a genetic mutation received from both parents. The
disease course is quite variable, ranging from no outward symptoms
to severe disability and death. Carrier status can be detected
through blood or saliva to identify potential carriers of the
Gaucher gene. Gaucher Disease can be diagnosed early through a
blood test.
Worldwide the diagnosed population of Gaucher Disease patients
is approximately 7,000. Based on incidence, the estimated total
world population is likely to be between 10,000 and 15,000
patients.
Notes to editors
SHIRE PLC
Shire's strategic goal is to become the leading specialty
biopharmaceutical company that focuses on meeting the needs of the
specialist physician. Shire focuses its business on attention
deficit hyperactivity disorder (ADHD), human genetic therapies
(HGT) and gastrointestinal (GI) diseases as well as opportunities
in other therapeutic areas to the extent they arise through
acquisitions. Shire's in-licensing, merger and acquisition efforts
are focused on products in specialist markets with strong
intellectual property protection and global rights. Shire believes
that a carefully selected and balanced portfolio of products with
strategically aligned and relatively small-scale sales forces will
deliver strong results.
For further information on Shire, please visit the Company's
website: http://www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION
REFORM ACT OF 1995
Statements included herein that are not historical facts are
forward-looking statements. Such forward-looking statements involve
a number of risks and uncertainties and are subject to change at
any time. In the event such risks or uncertainties materialize, the
Company's results could be materially adversely affected. The risks
and uncertainties include, but are not limited to, risks associated
with: the inherent uncertainty of research, development, approval,
reimbursement, manufacturing and commercialization of the Company's
Specialty Pharmaceutical and Human Genetic Therapies products, as
well as the ability to secure and integrate new products for
commercialization and/or development; government regulation of the
Company's products; the Company's ability to manufacture its
products in sufficient quantities to meet demand; the impact of
competitive therapies on the Company's products; the Company's
ability to register, maintain and enforce patents and other
intellectual property rights relating to its products; the
Company's ability to obtain and maintain government and other
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For further information please contact:
Investor Relations Clea Rosenfeld (Rest of the World) +44-1256-894-160
Eric Rojas (North America) +1-617-551-9715
Media Jessica Mann (Rest of the World) +44-1256-894-280
Jessica Cotrone (North America) +1-617-613-4640
Source: Shire Plc
For further information please contact: Investor Relations: Clea
Rosenfeld (Rest of the World) +44-1256-894-160, Eric Rojas (North
America) +1-617-551-9715; Media: Jessica Mann (Rest of the World)
+44-1256-894-280, Jessica Cotrone (North America)
+1-617-613-4640
Posted: August 2009
