ZUG, Switzerland, March 16, 2017 /PRNewswire/ --
CINRYZE
is now the first and only
Hereditary angioedema treatment
approved for routine prevention in
paediatrics
Shire plc (LSE: SHP, NASDAQ: SHPG) announced that the European
Commission (EC) has approved a label extension granting three new
indications for CINRYZE® (C1 inhibitor [human]),
broadening its use to children with Hereditary angiodema (HAE), a
rare, genetic disorder that results in recurring attacks of edema
(swelling).[1] The body sites most commonly affected are
mainly the extremities and
abdomen.[1] CINRYZE is now
indicated for routine prevention of angioedema attacks in children
(ages 6 years and above) with severe and recurrent attacks of HAE
who are intolerant to or insufficiently protected by oral
preventions treatments, or patients who are inadequately managed
with repeated acute treatment.[2] It is the first and
only HAE treatment with this indication in paediatric
patients.[2] CINRYZE is also now
approved for the treatment and pre-procedure prevention of
angioedema attacks in children (ages 2 years and above) with
HAE.[2]
Symptoms of HAE often present in childhood, and while attacks
can occur at any age, early onset may predict a more severe disease
course.[3] Attacks often occur in children without a
clear trigger,[2] and may affect a
child's participation in school, activities, and sports, which can
leave them feeling socially
isolated.[3],[4]
Less frequently, HAE can cause life-threatening attacks due to
obstruction in the upper
airways.[5],[6],[7]
"This paediatric label expansion demonstrates our ongoing
commitment to improving the lives of patients of all ages living
with HAE," said Philip J. Vickers,
Ph.D., Head of R&D, Shire. "We believe the future of HAE means
preventing attacks before they happen, and are proud to now be able
to offer the first long-term preventative treatment for paediatric
patients. As we expand our HAE portfolio, we remain focused on
innovative solutions that fulfil unmet needs for people worldwide
living with this rare disease."
CINRYZE has been approved since 2011 for these indications in
adults and adolescents ages 12-17 years with
HAE.[2]
Henrik Balle Boysen, Executive
Director of HAEi stated, "Over the years we have encountered many
children who suffer from frequent and severe HAE symptoms that
often occur spontaneously and without warning. Despite improvements
in the management of HAE in recent years, this new long-term
prophylaxis indication for alleviating the frequency of HAE
symptoms will be a welcome addition for families with HAE in
Europe."
CINRYZE will be available for use in paediatric patients later
in 2017 throughout Member States of the European Union (EU), as
well the European Economic Area (EEA) in which Shire currently has
a licence in the adult and adolescent population.
About HAE
HAE is a rare, genetic disorder that affects an estimated one in
50,000 people worldwide and results in recurring attacks of edema
(swelling).[8]
Long-term prophylaxis refers to the routine use of medication to
prevent episodes of angioedema, and may be considered for severely
symptomatic patients with HAE.[8]
Management of HAE also includes on-demand treatment of swelling
attacks (known as acute treatment) to minimise the consequences of
the symptoms, and pre-procedure prevention, which is often used
before certain surgeries and to cover other periods of high risk of
attack (such as stressful times including school examinations, for
example).[8]
Paediatric Study
Results[2]
The efficacy of CINRYZE for the treatment and prevention of
angioedema attacks in paediatric patients with HAE has been
demonstrated in two open-label studies (LEVP 2006-1 and
LEVP 2006-4) and two paediatric clinical studies (0624-203 and
0624-301).[2]
Two studies demonstrated the efficacy of CINRYZE for the
treatment of HAE in patients ages 6-11 years. The first study (LEVP
2006-1) included 22 paediatric patients (of a total of 101 enrolled
patients) who were treated for 121 acute HAE attacks. The
proportion of HAE attacks achieving unequivocal relief of the
defining symptom within four hours after treatment was
comparable between the 22 children (ages 2-17 years) and adults
enrolled in the study, with 89% and 86% of attacks achieving
relief, respectively.[2]
The second study (0624-203) enrolled nine paediatric patients
who received a single dose of CINRYZE based on their weight with
children weighing between 10 and 25 kg (n=3) receiving 500 units
and those weighing >25 kg receiving either 1000 units (n=3)
or 1500 units (n=3). All nine (100%) subjects achieved unequivocal
beginning of relief of the defining symptom within four hours
following initiation of treatment with
CINRYZE.[2] The 1500-unit dose is
not an approved dosage.
In addition, two studies demonstrated the efficacy of CINRYZE
for the prevention of HAE in paediatric patients. The first study
(LEVP 2006-4) included 23 paediatric patients (of a total of 146
enrolled patients) between the ages of 3 and 17 years. The children
received 1000 units of CINRYZE every three to seven days, with the
exception of a 3-year-old child who received 500 units every
three to seven days. Prior to enrolment, the children reported a
median of three HAE attacks each month. While receiving CINRYZE
prophylaxis during the study, 87% of the children reported an
average of one or fewer attack per month, which were comparable to
those observed in adults in the
study.[2]
The second study (0624-301) included six paediatric subjects
ages 6-11 years who were randomised to twice-weekly CINRYZE dosing
for 12 weeks in two treatment sequences (500/1000 units or 1000/500
units). Both doses resulted in similar reduction of
attack-frequency and showed clinical benefit regarding severity,
duration, and requirement for acute treatment of
attacks.[2]
For three subjects under the age of 6 years, administration of
CINRYZE (500 units or 1000 units) was associated with increases in
C1 INH levels and clinical efficacy in acute treatment and
prevention of attacks. Overall administration of CINRYZE was well
tolerated.[2]
Across clinical studies, there were 61 unique paediatric
subjects enrolled and exposed to over 2,500 infusions of CINRYZE
(2-5 years, n=3; 6-11 years, n=32; 12-17 years, n=26). Among these
children, adverse reactions with CINZYRE included headache, nausea,
pyrexia, and infusion site erythema. None of these adverse
reactions were severe, and none led to discontinuation of medicinal
product.[2] Overall, the safety
and tolerability of CINRYZE were similar in children, adolescents,
and adults.[2]
About CINRYZE
CINRYZE is the first and only C1 esterase inhibitor (C1-INH)
therapy approved for routine prevention in children, adolescents,
and adults with HAE. CINRYZE is also approved for acute treatment
and pre-procedure prevention of angioedema
attacks.[2]
The active substance in CINRYZE is C1-INH, which can restore
functional C1-INH levels in patients with
HAE.[2] Patients with HAE are
prone to swelling due to an underlying deficiency in
C1-INH.[6],[9]
C1-INH plays an integral role in the kinin-generating pathway and
controls the production of the protein
bradykinin.[1],[9],[10],[11]
During a swelling attack, overproduction of bradykinin increases
the permeability of blood vessels, causing fluids to "leak" into
the surrounding tissue, resulting in
swelling.[1],[13]
Treatment with C1-INH raises the plasma level of C1-INH and helps
regulate the production of bradykinin released during an
attack.[2],[12],[13]
CINRYZE is administered intravenously and may be
self-administered.[2] The decision
on the use of home-treatment for an individual patient should be
made by the treating physician, who should ensure that appropriate
training is provided and the use reviewed at
intervals.[2] CINRYZE therapy
should be initiated under supervision of a physician experienced in
the care of patients with
HAE.[2]
For treatment of angioedema attacks in adolescents (ages 12-17
years) and adults, a dose of 1000 units of CINRYZE is given at the
first sign of the onset of an
attack.[2] A second dose of 1000
units may be administered if the patient has not responded
adequately after 60 minutes.[2]
For patients experiencing laryngeal attacks, or if the initiation
of treatment is delayed, the second dose can be given sooner than
60 minutes.[2]
For routine prevention of angioedema attacks in adolescents
(ages 12-17 years) and adults, 1000 units of CINRYZE every 3 or 4
days is the recommended starting
dose.[2] The dosing interval may
need to be adjusted according to individual
response.[2] The continued need
for regular prophylaxis with CINRYZE should be reviewed on a
regular basis.[2]
For pre-procedure prevention of angioedema attacks in
adolescents (ages 12-17 years) and adults, 1000 units of CINRYZE is
given within 24 hours before a medical, dental, or surgical
procedure.[2]
For treatment of angioedema attacks in children (ages 2-11
years) who weigh more than 25 kg, a dose of 1000 units of CINRYZE
is given at the first sign of the onset of an
attack.[1] A second dose of 1000
units may be administered if the patient has not responded
adequately after 60 minutes.[1]
For children who weigh between 10 to 25 kg, the starting dose is
500 units with a second dose of 500 units if the patient has not
responded adequately after 60
minutes.[1]
For pre-procedure prevention of angioedema attacks in children
(ages 2-11 years) who weigh more than 25 kg, 1000 units of CINRYZE
is given within 24 hours before a medical, dental, or surgical
procedure.[1] For children
weighing between 10 to 25 kg, the dose is 500
units.[1]
For routine prevention of angioedema attacks (ages 6-11 years),
500 units of CINRYZE every three or four days is the recommended
starting dose (regardless of
weight).[1] The dosing interval
may need to be adjusted according to individual response. The
continued need for regular prophylaxis with CINRYZE should be
reviewed on a regular
basis.[1]
Safety and Tolerability
The only common (i.e., ≥1/100 to <1/10) adverse reaction
observed following CINRYZE infusion in clinical studies was rash;
descriptions of rash characteristics were non-specific, but were
typically described as involving the upper extremities, chest,
abdomen, or injection site.[2]
None of the rashes were serious, and none led to discontinuation of
medicinal product.[2]
Contraindications
CINRYZE is contraindicated in patients who are hypersensitive to
the active ingredients or any
excipients.[2]
Special Warnings and Precautions for
Use[2]
- Thrombotic events have been reported in neonatal and infant
subjects undergoing cardiac bypass procedures while receiving
off-label high doses of another C1 inhibitor product (up to 500
units/kg) to prevent capillary leak syndrome. Based upon an animal
study there is a potential thrombogenic threshold at doses greater
than 200 units/kg. Patients with known risk factors for thrombotic
events (including indwelling catheters) should be monitored
closely.
- Thrombotic events have been reported in neonatal and infant
subjects undergoing cardiac bypass procedures while receiving
off-label high doses of another C1 inhibitor product (up to 500
units/kg) to prevent capillary leak syndrome.
- Standard measures to prevent infections resulting from the use
of medicinal products prepared from human blood or plasma include
selection of donors, screening of individual donations and plasma
pools for specific markers of infection, and the inclusion of
effective manufacturing steps for the inactivation/removal of
viruses. Despite this, when medicinal products prepared from human
blood or 4 plasma are administered, the possibility of transmitting
infective agents cannot be totally excluded. This also applies to
unknown or emerging viruses and other pathogens. The measures taken
are considered effective for enveloped viruses such as HIV, HBV,
and HCV, and for the non-enveloped viruses HAV and parvovirus B19.
Appropriate vaccination (hepatitis A and B) should be considered
for patients in regular/repeated receipt of human plasma-derived C1
inhibitor product. It is strongly recommended that every time
CINRYZE is administered to a patient, the name and batch number of
the product are recorded in order to maintain a link between the
patient and the batch of the product.
- As with any biological product hypersensitivity reactions may
occur. Hypersensitivity reactions may have symptoms similar to
angioedema attacks. Patients should be informed of the early signs
of hypersensitivity reactions including hives, generalised
urticaria, tightness of the chest, wheezing, hypotension, and
anaphylaxis. If these symptoms occur after administration, they
should alert their physician. In case of anaphylactic reactions or
shock, emergency medical treatment should be administered.
- There are limited data on the use of this medicinal product in
home- or self-administration. Potential risks associated with
home-treatment are related to the administration itself as well as
the handling of adverse drug reactions, particularly
hypersensitivity. The decision on the use of home-treatment for an
individual patient should be made by the treating physician, who
should ensure that appropriate training is provided and the use
reviewed at intervals.
- Each vial of CINRYZE contains approximately 11.5 mg of sodium.
To be taken into consideration by patients on a controlled sodium
diet.
NOTES TO EDITOR
About Shire
Shire is the leading global biotechnology company focused on
serving people with rare diseases and other highly specialised
conditions. We strive to develop best-in-class products, many of
which are available in more than 100 countries, across core
therapeutic areas including Haematology, Immunology, Neuroscience,
Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal /
Internal Medicine / Endocrine and Hereditary Angioedema; and a
growing franchise in Oncology.
Our employees come to work every day with a shared mission: to
develop and deliver breakthrough therapies for the hundreds of
millions of people in the world affected by rare diseases and other
high-need conditions, and who lack effective therapies to live
their lives to the fullest.
http://www.shire.com
Forward-Looking Statements
Statements included herein that are not historical facts,
including without limitation statements concerning future strategy,
plans, objectives, expectations and intentions, the anticipated
timing of clinical trials and approvals for, and the commercial
potential of, inline or pipeline products, 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, Shire's results
could be materially adversely affected. The risks and uncertainties
include, but are not limited to, the following:
- Shire's products may not be a commercial success;
- increased pricing pressures and limits on patient access as a
result of governmental regulations and market developments may
affect Shire's future revenues, financial condition and results of
operations;
- Shire conducts its own manufacturing operations for certain of
its products and is reliant on third party contract manufacturers
to manufacture other products and to provide goods and services.
Some of Shire's products or ingredients are only available from a
single approved source for manufacture. Any disruption to the
supply chain for any of Shire's products may result in Shire being
unable to continue marketing or developing a product or may result
in Shire being unable to do so on a commercially viable basis for
some period of time;
- the manufacture of Shire's products is subject to extensive
oversight by various regulatory agencies. Regulatory approvals or
interventions associated with changes to manufacturing sites,
ingredients or manufacturing processes could lead to, among other
things, significant delays, an increase in operating costs, lost
product sales, an interruption of research activities or the delay
of new product launches;
- certain of Shire's therapies involve lengthy and complex
processes, which may prevent Shire from timely responding to market
forces and effectively managing its production capacity;
- Shire has a portfolio of products in various stages of research
and development. The successful development of these products is
highly uncertain and requires significant expenditures and time,
and there is no guarantee that these products will receive
regulatory approval;
- the actions of certain customers could affect Shire's ability
to sell or market products profitably. Fluctuations in buying or
distribution patterns by such customers can adversely affect
Shire's revenues, financial conditions or results of
operations;
- Shire's products and product candidates face substantial
competition in the product markets in which it operates, including
competition from generics;
- adverse outcomes in legal matters, tax audits and other
disputes, including Shire's ability to enforce and defend patents
and other intellectual property rights required for its business,
could have a material adverse effect on the combined company's
revenues, financial condition or results of operations;
- inability to successfully compete for highly qualified
personnel from other companies and organizations;
- failure to achieve the strategic objectives, including expected
operating efficiencies, cost savings, revenue enhancements,
synergies or other benefits at the time anticipated or at all with
respect to Shire's acquisition of NPS Pharmaceuticals Inc., Dyax
Corp. or Baxalta Incorporated may adversely affect Shire's
financial condition and results of operations;
- Shire's growth strategy depends in part upon its ability to
expand its product portfolio through external collaborations,
which, if unsuccessful, may adversely affect the development and
sale of its products;
- a slowdown of global economic growth, or economic instability
of countries in which Shire does business, as well as changes in
foreign currency exchange rates and interest rates, that adversely
impact the availability and cost of credit and customer purchasing
and payment patterns, including the collectability of customer
accounts receivable;
- failure of a marketed product to work effectively or if such a
product is the cause of adverse side effects could result in damage
to Shire's reputation, the withdrawal of the product and legal
action against Shire;
- investigations or enforcement action by regulatory authorities
or law enforcement agencies relating to Shire's activities in the
highly regulated markets in which it operates may result in
significant legal costs and the payment of substantial compensation
or fines;
- Shire is dependent on information technology and its systems
and infrastructure face certain risks, including from service
disruptions, the loss of sensitive or confidential information,
cyber-attacks and other security breaches or data leakages that
could have a material adverse effect on Shire's revenues, financial
condition or results of operations;
- Shire incurred substantial additional indebtedness to finance
the Baxalta acquisition, which may decrease its business
flexibility and increase borrowing costs; and
a further list and description of risks, uncertainties and other
matters can be found in Shire's most recent Annual Report on Form
10-K and in Shire's subsequent Quarterly Reports on Form 10-Q, in
each case including those risks outlined in "ITEM 1A: Risk
Factors", and in subsequent reports on Form 8-K and other
Securities and Exchange Commission filings, all of which are
available on Shire's website.
All forward-looking statements attributable to us or any person
acting on our behalf are expressly qualified in their entirety by
this cautionary statement. Readers are cautioned not to place undue
reliance on these forward-looking statements that speak only as of
the date hereof. Except to the extent otherwise required by
applicable law, we do not undertake any obligation to update or
revise forward-looking statements, whether as a result of new
information, future events or otherwise.
▼This medicinal product is subject to additional
monitoring. This will allow quick identification of new safety
information. Healthcare professionals are asked to report any
suspected adverse reactions. See section 4.8 of the Summary of
Product Characteristics for how to report adverse reactions.
References
1. Bork K, Davis-Lorton M.
Overview of hereditary angioedema caused by C1-inhibitor
deficiency: assessment and clinical management. Eur Ann Allergy
Clin Immunol 2013; 45(1):7-16.
2. CINRYZE (C1 Inhibitor [human]) Summary of Product
Characteristics. January 2017.
Document on File at Shire.
3. Farkas H, et al. International consensus on the diagnosis
and management of paediatric patients with hereditary angioedema
with C1 inhibitor deficiency. Allergy. 2017; 72(2):300-13.
4. Read N, et al. Patient hereditary angioedema: a survey of
UK service provision and patient experience. Clin Exp Immunol 2014;
178:473-88.
5. Donaldson V, Evans R. A biochemical abnormality in
hereditary angioneurotic edema: absence of serum inhibitor of
C1-esterase. Am J Med. 1963; 35:37-44.
6. Bork K, et al. Hereditary angioedema: New findings
concerning symptoms, affected organs, and course. Am J Med 2006;
119(3):267-74.
7. Bork K. Fatal laryngeal attacks and mortality in
hereditary angioedema due to C1-INH deficiency. JAACI 2012; DOI:
http://dx.doi.org/10.1016/j.jaci.2012.05.055.
8. Craig T, et al. WAO guideline for the management of
hereditary angioedema. World Allergy Organ Journal 2012;
5(12):182-99.
9. Lung C, et al, Analysis of an exon 1 polymorphism of the
B2 bradykinin receptor gene and its transcript in normal subjects
and patients with C1 inhibitor deficiency. Allergy, Asthma Clin
Immunol 1997; 99(1):134-146.
10. Nussberger J, et al. Local bradykinin generation in
hereditary angioedema. Allergy Asthma Clin Immunol 1999;
104(6):1321-1322.
11. Bjorkqvist J, et al. Hereditary angioedema: a
bradykinin-mediated swelling disorder. Thromb Haemost 2013;
109:368-374.
12. Nussberger J, et al. Plasma bradykinin in angio-edema.
The Lancet 1998; 351:1693-1697.
13. Kaplan AP, Joseph K. The bradykinin-forming cascade and
its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010;
104:193.
For Further Information, Please Contact
Investor Relations
Ian Karp, ikarp@shire.com, +1-781-482-9018
Robert Coates, rcoates@shire.com, +44-1256-894874
Media
Annabel
Cowper, annabel.cowper@shire.com, +41-44-878-6638