Swedish Orphan Biovitrum AB (publ): New phase 3 data confirm long-lasting characteristics of rFIXFc and rFVIIIFc across multiple haemophilia populations
Interim analyses from phase 3 paediatric studies suggest prolonged half-life of
investigational long-lasting therapies in children under age 12.
Today Biogen Idec (NASDAQ: BIIB) and Swedish Orphan Biovitrum (Sobi) (STO: SOBI)
announced new results from Phase 3 studies of their investigational long-lasting
recombinant factor IX and VIII Fc fusion protein candidates for haemophilia B
and A, rFIXFc (ALPROLIX(TM)) and rFVIIIFc (ELOCTATE(TM)), including an interim
analysis of paediatric pharmacokinetics (PK) data. These interim data are the
first to demonstrate that rFIXFc and rFVIIIFc have consistently prolonged half-
lives (a measure of the time therapy circulates in the bloodstream) in children,
compared to study participants' prior therapies. Investigators presented these
results, which were consistent with PK results in adults and adolescents, at the
55(th) Annual Meeting of the American Society of Hematology (ASH) in New
Orleans, held on 7 to 10 December.
rFIXFc and rFVIIIFc use a technology called Fc fusion and demonstrate prolonged
circulation in the body, which has been shown in studies of adults with
haemophilia to extend the time between prophylactic infusions.
"As seen in adult studies, interim data demonstrated that in children, the use
of Fc fusion technology prolongs the half-lives of these experimental
therapies," said Guy Young, M.D., director, Hemostasis and Thrombosis Centre,
Children's Hospital Los Angeles. "We are investigating whether prophylactic
dosing intervals longer than the currently available therapy are possible with
these treatments. The frequency of traditional prophylactic regimens is a
significant challenge for parents of children with haemophilia, many of whom
require infusions multiple times per week."
Kids B-LONG and Kids A-LONG are on-going, multi-centre Phase 3 studies of rFIXFc
and rFVIIIFc for previously treated children under age 12 with haemophilia B and
A, respectively. Kids B-LONG and Kids A-LONG are designed to investigate the
safety, efficacy and PK of rFIXFc and rFVIIIFc. In Kids B-LONG, the mean half-
life of rFIXFc was more than three times longer than currently available factor
IX therapies. The Kids A-LONG interim analysis showed the mean half-life of
rFVIIIFc was approximately one and a half times that of existing factor VIII
therapies. For both rFIXFc and rFVIIIFc, prolonged half-lives were seen in each
age group analysed - under six and six to under 12 years old.
In 43 children treated with rFVIIIFc as of February 8, 2013, and 23 children
receiving rFIXFc as of April 23, 2013, no inhibitors (antibodies that may
interfere with the activity of the therapy) were detected. Overall, the pattern
of treatment-emergent adverse events reported was typical of the populations
studied, with no unique safety issues identified.
Final results of the paediatric studies will evaluate the safety and efficacy of
rFIXFc and rFVIIIFc, as well as provide further PK information. Investigators
plan to report these results at a future medical meeting. The primary endpoint
for both studies is the occurrence of inhibitor development over the study
period. Secondary outcome measures include the annualized bleeding rate (ABR),
or projected number of yearly bleeding episodes, and assessments of response to
treatment.
At the meeting, new analyses of data from B-LONG and A-LONG, the Phase 3 studies
of rFIXFc and rFVIIIFc in adolescents and adults, were presented. These data
provided additional insight into the prophylactic dosing regimens that may be
possible with these therapies, if approved. Prophylaxis regimens involve
regularly scheduled infusions designed to prevent or reduce bleeding episodes.
In these studies, a prolonged half-life helped study participants achieve
effective prevention or reduction of bleeding episodes with fewer prophylactic
infusions.
"These data underscore our commitment to advancing scientific understanding and
innovation in haemophilia, and our goal of introducing the first long-lasting
therapies to those with haemophilia," said Glenn Pierce, M.D., Ph.D., senior
vice president of Global Medical Affairs and chief medical officer at Biogen
Idec's haemophilia therapeutic area. "These analyses add to the growing body of
data supporting the clinical benefits of rFIXFc and rFVIIIFc in people of
different ages with haemophilia B and A, and their potential to reduce bleeding
episodes with fewer prophylactic infusions, if approved."
Less Frequent Prophylactic Dosing Observed with rFVIIIFc
A post-hoc analysis of A-LONG participants who were receiving a prophylactic
(preventive) regimen with currently available factor VIII therapies prior to the
study, evaluated self-reported dose, dose interval and bleeding rates over the
preceding 12 months while on currently approved factor VIII therapies. These
data points were also collected for on-study rFVIIIFc therapy.
The majority of participants reported infusions three times a week with their
previous factor VIII therapy. During the study, 98.8 percent of participants had
rFVIIIFc prophylactic dosing regimens with less frequent infusions than they
reported using before the study. Their last on-study prophylactic dosing
intervals were every three days (36.3 percent), twice weekly (28.8 percent),
every four days (5.0 percent) and every five days (30.0 percent). Overall, these
participants reported a median of 6.0 bleeding episodes in the prior year with
their existing therapy; in the last three months of on-study rFVIIIFc therapy,
they had a median annualized bleeding rate of zero. Weekly factor consumption
for prophylaxis remained consistent with rFVIIIFc and prior therapy for the
majority of participants.
"Prophylactic dosing schedules have the potential to be less frequent and reduce
bleeding episodes with the emergence of long-lasting therapy," said Birgitte
Volck, M.D., Ph.D., senior vice president development and chief medical officer
of Sobi. "These data may help physicians understand how prophylactic dosing
schedules could differ between investigational, long-lasting rFVIIIFc therapy
and currently available factor VIII treatments. The post-hoc analysis showed
that rFVIIIFc enabled bleeding control for study participants with less frequent
prophylactic infusions than their previous therapy."
Study investigators reported that rFVIIIFc was well tolerated, and no inhibitors
were detected during the A-LONG study. Safety events were representative of
those occurring in the general haemophilia population. Outside of the
perioperative (surgical) period, the most common adverse events (incidence of
greater than or equal to five per cent) included nasopharyngitis (common cold),
arthralgia (joint pain), headache and upper respiratory infection.
Haemophilia Quality of Life Measure Validated
This study evaluated the reliability, validity and sensitivity of the
Haemophilia-Specific Quality of Life Index (Haem-A-QoL), a 46-item questionnaire
used to assess health-related quality of life specifically in people with
haemophilia. The analysis used EuroQoL-5 Dimension (EQ-5D) data to validate
Haem-A-QoL data collected from participants in the A-LONG and B-LONG studies.
EQ-5D is a quality-of-life health assessment tool that is commonly used in late-
stage studies for other diseases. These data further validate the usefulness of
the Haem-A-QoL measurement in adults with haemophilia.
"Without adequate control over bleeding episodes, haemophilia not only leads to
physical complications, but also may impact a person's ability to attend work or
school, enjoy leisure activities or maintain positive mental health," said Aoife
Brennan, M.D., senior medical director, Clinical Development of Biogen Idec's
haemophilia therapeutic area. "To understand these effects, we are committed to
examining the impact of our investigational therapies rFIXFc and rFVIIIFc on a
broad range of measurements, including quality-of-life measurement tools. A
preliminary analysis of Haem-A-QoL scores in A-LONG and B-LONG showed numerical
improvements in total scores from baseline, and we are conducting further
analyses to understand the potential clinical implications of these results."
About rFIXFc and rFVIIIFc
rFIXFc (ALPROLIX) and rFVIIIFc (ELOCTATE) are investigational fully recombinant,
long-lasting clotting factor therapies being developed for haemophilia B and A,
respectively. They use Fc fusion technology, which takes advantage of a
naturally occurring pathway that delays the breakdown of Immunoglobulin G
Subclass 1, or IgG1 (protein commonly found in the body), and cycles it back
into the bloodstream. The Fc portion of IgG1 is fused to factors IX and VIII in
rFIXFc and rFVIIIFc, respectively. This technology is thought to be responsible
for the prolonged time rFIXFc and rFVIIIFc circulate in the body. While Fc
fusion is an established technology that has been used for more than 15 years,
Biogen Idec is the only company to apply it in haemophilia.
Based on Phase 3 study results, prophylactic therapy with rFIXFc and rFVIIIFc
may help prevent or reduce bleeding episodes in people with severe haemophilia B
and A, respectively. Regulatory applications for both therapies are currently
under review in several countries including the United States, Canada and
Australia.
About Haemophilia A and B
Haemophilia is a rare, inherited disorder in which the ability of a person's
blood to clot is impaired. Haemophilia A occurs in about one in 5,000 male
births annually, and more rarely in females, affecting about 16,000 people in
the United States. Haemophilia B occurs in about one in 25,000 male births
annually, and more rarely in females, affecting about 3,300 people in the United
States. According to the World Federation of Haemophilia, an estimated 400,000
people worldwide are living with haemophilia.
Haemophilia A is caused by having substantially reduced or no factor VIII
activity, while haemophilia B is caused by having substantially reduced or no
factor IX activity; factor VIII and factor IX are needed for normal blood
clotting. People with haemophilia A or B experience prolonged bleeding episodes
that can cause pain, irreversible joint damage and life-threatening
haemorrhages. Prophylactic infusions of factor VIII or IX can temporarily
replace the missing clotting factors that are needed to control bleeding and
prevent new bleeding episodes. The Medical and Scientific Advisory Council of
the National Hemophilia Foundation recommends prophylaxis as the optimal therapy
for people with severe haemophilia A or B.
About the Biogen Idec and Sobi Collaboration
Biogen Idec and Swedish Orphan Biovitrum (Sobi) are partners in the development
and commercialization of ALPROLIX for haemophilia B. Biogen Idec leads
development, has manufacturing rights, and has commercialization rights in North
America and all other regions excluding the Sobi territory. Sobi has the right
to opt in to assume final development and commercialization in Europe (including
Russia), the Middle East and Northern Africa.
About Biogen Idec
Through cutting-edge science and medicine, Biogen Idec discovers, develops and
delivers to patients worldwide innovative therapies for the treatment of
neurodegenerative diseases, haemophilia and autoimmune disorders. Founded in
1978, Biogen Idec is the world's oldest independent biotechnology company.
Patients worldwide benefit from its leading multiple sclerosis therapies, and
the company generates more than $5 billion in annual revenues. For product
labelling, press releases and additional information about the company, please
visit www.biogenidec.com.
About Sobi
Sobi is an international specialty healthcare company dedicated to rare
diseases. Our mission is to develop and deliver innovative therapies and
services to improve the lives of patients. The product portfolio is primarily
focused on inflammation and genetic diseases, with three late stage biological
development projects within haemophilia and neonatology. We also market a
portfolio of specialty and rare disease products for partner companies. Sobi is
a pioneer in biotechnology with world-class capabilities in protein biochemistry
and biologics manufacturing. In 2012, Sobi had total revenues of SEK 1.9 billion
(€ 215 M) and about 500 employees. The share (STO: SOBI) is listed on NASDAQ OMX
Stockholm. More information is available at www.sobi.com.
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about the potential advances, impact and therapeutic effect of ALPROLIX, our
investigational long-lasting recombinant factor IX candidate. These statements
may be identified by words such as "believe," "expect," "may," "plan,"
"potential," "will" and similar expressions, and are based on our current
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arise from additional data or analysis, regulatory authorities may require
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Charlotte af Klercker Jörgen Winroth
T: +46 70 729 7327 T:
+1 347-224-0819, +1 212-579-0506, +46 8 697 2135
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