Shire Presents Positive Data for Patients with Type 1 Gaucher Disease Who Switched to VPRIV
Also Reported are Results of Retrospective Analysis of Phase I/II Study, Showing Success in Reaching Therapeutic Goals within 4 Years of Initiation of Treatment
CAMBRIDGE, Massachusetts, March 25, 2010/PRNewswire-FirstCall/
-- Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today presented positive data from a
Phase III clinical trial (TKT-034) designed to evaluate the safety
of switching to VPRIV (velaglucerase alfa for injection), from
imiglucerase, as well as an interim analysis of safety data from an
ongoing multicenter open-label treatment protocol (HGT-GCB-058)
implemented to provide VPRIV to patients affected by the continuing
shortage of imiglucerase. A post-hoc analysis of Phase I/II data on
therapeutic goal attainment was also presented at the 2010 American
College of Medical Genetics Annual Clinical Genetics Meeting in
Albuquerque, New Mexico. These data add to the growing body of
clinical evidence which support the use of VPRIV in patients both
transitioning from imiglucerase or who are treatment naive.
Adult and pediatric patients with Type 1 Gaucher disease were
switched from imiglucerase (15-60 U/kg every other week) to the
same number of units of VPRIV in the Phase III switch study (40
patients) and the ongoing US treatment protocol (>150 patients).
In study TKT-034, no patients developed IgG antibodies to VPRIV,
including 3 patients who tested positive for anti-imiglucerase
antibodies at screening. In addition, hemoglobin concentration,
platelet counts, and liver and spleen volumes remained stable over
the course of the one year study, demonstrating safety and
maintenance of efficacy over this time frame. One patient in the
Phase III trial discontinued due to a serious hypersensitivity
reaction and the most common side effects reported in the two
studies were infusion-related reactions.
"Results from the Phase III study provide important information
regarding the safety and sustained efficacy of VPRIV for patients
with Type 1 Gaucher disease who were previously on imiglucerase and
should help inform treatment decisions during and after the
imiglucerase supply shortage," said Dr. Gregory Grabowski, Director
of the Division of Human Genetics, Cincinnati Children's Hospital
Medical Center and Principal Investigator of the 034 study. "These
data confirm what many physicians have experienced."
A post hoc analysis from a third study, TKT-025EXT, designed to
examine attainment of long-term therapeutic goals in 8 patients
with Type 1 Gaucher disease treated with velaglucerase alfa, was
also presented at the meeting. The initial dose of 60 U/kg was
lowered to 30 U/kg after patients achieved at least 2 of 4
predefined therapeutic goals following 1 year of treatment.
Clinically meaningful achievement of long-term therapeutic goals
for hemoglobin concentration, platelet counts, and liver and spleen
volumes was observed within 4 years of initiation of
treatment.
Shire also reported important findings that suggested
substantial antigenic differences when antibody response to
treatment with VPRIV and imiglucerase were compared. Among the 99
patients who enrolled in the Phase III studies the seroconversion
rate was 1% (1 of 82) against VPRIV versus 23% (4 of 17) against
imiglucerase.
Velaglucerase alfa is manufactured in Shire's facility in
Cambridge MA, which was inspected and approved by the FDA for the
commercial production of VPRIV.
Study Results and Design for TKT-034, HGT-GBC-058 and
TKT-025EXT
TKT-034
In this global, open-label, multicenter study, patients were
enrolled in the US (11 sites), Europe (3 sites) and Israel (1
site), and of the 41 patients enrolled, 40 received study drug. One
patient discontinued due to a serious hypersensitivity reaction and
one patient discontinued at week 31 due to a perceived lack of
improvement. At the time of discontinuation, this patient's
clinical parameters were stable and consistent with those of the
entire group of patients in the study.
Hemoglobin concentration, platelet counts, and spleen and liver
volume were sustained at therapeutic levels through one year of
treatment with VPRIV, as demonstrated by pre-specified efficacy
criteria for clinically significant change:
- Hemoglobin concentration: the mean change from baseline was -0.1 g/dL,
with a 90 percent confidence interval of -0.3 to 0.1 g/dL, within the
predefined efficacy criterion of plus or minus 1 g/dL.
- Platelet counts: the percent change from baseline was +7.0%, with a 90
percent confidence interval of 0.5 to 13.5%, within the predefined
efficacy criterion of plus or minus 20%.
- Spleen volume: the percent change from baseline was -5.6%, with a 90
percent confidence interval of -10.8 to -0.4% within the predefined
efficacy criterion of plus or minus 15%.
- Liver volume: the percent change from baseline was -0.0%, with a 90
percent confidence interval of -2.6 to 2.6% within the predefined
efficacy criterion of plus or minus 15%.
Study design
The primary objective of TKT-034 was to evaluate the safety of
VPRIV in patients with Type 1 Gaucher disease who transitioned from
imiglucerase to VPRIV. The secondary objectives were to evaluate
changes from baseline in hemoglobin concentration, platelet counts,
and spleen and liver volumes by Magnetic Resource Imaging (MRI)
after every other week dosing of VPRIV.
Patients over the age of two years and receiving imiglucerase at
a dose between 15 and 60 U/kg every other week for at least 30
months with no dose change in the last 6 months were eligible,
provided they had demonstrated stable hemoglobin concentration and
platelet counts. Patients were infused in one hour with the same
number of units of VPRIV as their prior imiglucerase dose.
HGT-GCB-058
This ongoing multicenter, open-label treatment protocol was
initiated at the request of the Food and Drug Administration (FDA)
to provide VPRIV to patients who otherwise have limited or no
access to imiglucerase due to a continuing supply shortage.
Between September 1, 2009 and January 31, 2010, more than 150
patients in the US enrolled into HGT-GCB-058 and received at least
one infusion of VPRIV. Of these, 3 were treatment naive and the
rest were previously treated with imiglucerase. Following the
administration of the first three infusions of VPRIV at the
clinical site, patients who experienced no treatment-related
serious adverse events or infusion-related adverse events were
eligible to transition to home therapy at the discretion of the
investigator. Patients were required to return to the clinic site
quarterly for observation.
An interim safety analysis of the more than 150 patients on the
treatment protocol was conducted. Among those patients previously
treated with imiglucerase, a total of 18% experienced a treatment
emergent adverse event that was possibly or probably related to the
study drug. The most commonly observed treatment emergent adverse
events among switch patients included at least one infusion-related
reaction, nasopharyngitis, nausea, fatigue, headache, dizziness and
influenza. Approximately 1% of patients experienced a severe
adverse event that was considered to be possibly or probably
related to the study drug.
TKT-025EXT: Study Results and Design of Therapeutic Goal
Analysis
This post-hoc analysis of data from the Phase I/II and extension
trial of velaglucerase alfa showed that clinically meaningful
long-term therapeutic goals were achieved within 4 years of
initiation of velaglucerase alfa treatment.
The efficacy parameters were evaluated against the therapeutic
goals described by Pastores et al (Seminars in Hematology, 2004)
aand included absolute and percent changes in hemoglobin levels,
platelet counts, and spleen and liver volumes as measured by MRI.
Evaluation in this study was limited to those patients who were
exposed to velaglucerase alfa for a minimum of 48 months and for
whom a complete clinical data set corresponding to the study
endoints was available at baseline and annually through 48 months
(8 patients, 4 male, 4 female). Patients were evaluated for the
achievement of each individual therapeutic goal. The percentage of
patients achieving each specific goal over time was determined. In
addition the percentage of patients with a complete response
(achieved all 4 therapeutic goals) over time was also
evaluated.
At baseline, no patient was at goal for all 4 clinical
parameters: 4 of 8 patients were at goal for hemoglobin
concentration, 0 of 8 for platelet count, 4 of 8 for liver volume,
and 0 of 8 for spleen volume. After 1 year of treatment, all
patients achieved at least 2 therapeutic goals, and all patients
maintained clinical parameters for goals that were already at the
recommended targets when treatment began. All 8 patients were
eligible for and began step-wise dose reduction to velaglucerase
alfa 30 U/kg EOW starting between 12 and 18 months. By year 4 of
treatment, all patients met goals for all 4 clinical parameters;
therefore, 100% achievement was observed for each of the 4
long-term, therapeutic goals.
More about VPRIV
VPRIV (velaglucerase alfa for injection) was approved by the US
FDA as a long-term enzyme replacement therapy for adult and
pediatric patients with Type 1 Gaucher disease on February 26,
2010. A marketing application for VPRIV has also been granted
accelerated assessment by the European Medicines Agency in the
European Union (EU). Shire expects to launch VPRIV in the EU by the
end of 2010 and in other countries beginning in 2011.
VPRIV is for patients who are treatment naive as well as
patients who have been treated with imiglucerase. The most serious
adverse reactions seen with VPRIV were hypersensitivity reactions.
Infusion-related reactions were the most commonly observed adverse
reactions in patients treated with VPRIV in clinical studies. The
most commonly observed symptoms of infusion-related reactions were:
headache, dizziness, low or high blood pressure, nausea, tiredness
and weakness, and fever. Generally the infusion-related reactions
were mild and, in treatment-naive patients, onset occurred mostly
during the first 6 months of treatment and tended to occur less
frequently with time. Adverse reactions more commonly seen in
pediatric patients compared to those observed in adult patients
(>10% difference) include rash, upper respiratory tract
infection, prolonged activated partial thromboplastin time, and
fever.
As with all therapeutic proteins, there is a potential for
immunogenicity. In the clinical studies 1 of 54 treatment-naive
patients treated with VPRIV developed IgG class antibodies. It is
unknown if the presence of IgG antibodies to VPRIV is associated
with a higher risk of infusion reactions.
Full prescribing information for VPRIV can be found at
http://www.VPRIV.com.
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.
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well as the ability to secure and integrate new products for
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For further information please contact:
Investor Relations
Clea Rosenfeld (Rest of the World), +44-1256-894-160
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Media
Jessica Mann (Rest of the World), +44-1256-894-280
Jessica Cotrone (North America, HGT), +1-781-482-9538
Source: Shire plc
For further information please contact: Investor Relations: Clea
Rosenfeld (Rest of the World), +44-1256-894-160; Eric Rojas (North
America), +1-781-482-0999; Media: Jessica Mann (Rest of the World),
+44-1256-894-280; Jessica Cotrone (North America, HGT),
+1-781-482-9538
Posted: March 2010
