LEXINGTON, Massachusetts,
December 2, 2016 /PRNewswire/ --
Shire plc (LSE: SHP; NASDAQ: SHPG), the leading
biotechnology company focused on serving individuals with rare
diseases, is presenting an update on its safety database describing
40 years of real-world experience with the bypassing agent FEIBA
[Anti-Inhibitor Coagulant Complex]. Shire also revealed new in
vitro data showing the potential for excessive thrombin
generation when combining an investigational procoagulant
bispecific antibody and bypass therapy for breakthrough bleeds.
These data are now available online as part of the Proceedings of
the 58th American Society of Hematology (ASH) Annual Meeting, to be
held December 3-6 in San Diego, California.
Inhibitors are a rare but serious complication impacting about
5-7 percent of patients with hemophilia A. They form when the
body's immune system attacks the molecules in factor therapy,
causing it to be
ineffective.[1],[2]
Bypassing agents help bypass the inhibitor to help the body form a
clot and stop bleeding.[3]
Recently, concerns have emerged related to the use of an
investigational non-factor product when combined with marketed
bypassing agents for hemophilia patients with inhibitors. Shire
conducted an analysis of a sequence analogue biosimilar of one
investigational agent, emicizumab, in combination with bypassing
agents. Researchers characterized in vitro the rate and
level of thrombin generation resulting from combining the bypassing
agent and investigational non-factor product. The data found a
multi-fold increase in thrombin generation, indicating a potential
thrombotic risk for patients who receive the investigational agent
combined with an approved bypass agent for breakthrough bleeds.
(Synergistic Effects of a Procoagulant Bispecific Antibody and
Rescue Therapies on Thrombin Generation- a Potential Safety
Risk,
http://www.bloodjournal.org/content/128/22/4952.)[4]
"FEIBA is a widely approved treatment option for people with
hemophilia A and B with inhibitors, and has a well-established
safety and efficacy profile[5],"
said Leonard Valentino, M.D., Global
Head of Hematology Medical Affairs, Shire. "Shire embraces new
products with the potential to build on current standards of
hemophilia care. As with any new product, rigorous clinical studies
and careful review of safety and efficacy data are crucial to
inform healthcare providers and patients on the best way to safely
and effectively incorporate potential new therapeutic agents into
existing management strategies."
Shire continually evaluates the safety profile of its products
through ongoing safety surveillance. The risk of thromboembolic
events (TEEs) is well characterized in the FEIBA label. FEIBA has a
boxed warning for identified thromboembolic
risk.[5] Approximately three TEEs
have been reported per 100,000 infusions based upon more than seven
billion units (equivalent to about two million infusions)
distributed over the past 40
years.[6]
During ASH, Shire is presenting an update on its safety database
describing the real-world experience with FEIBA. The global review
of safety databases for AE reports of FEIBA received from 1975
through July 2016 showing the
reporting rate of TEEs associated with FEIBA is comparable with
previously reported data. (Four Decade Cumulative Review of
Thrombo-Embolic Events Reported with the Use of Activated
Prothrombin Complex Concentrate in Congenital Haemophilia,
http://www.bloodjournal.org/content/128/22/503.)[6]
Indications for FEIBA [Anti-Inhibitor Coagulant
Complex]
FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use
in hemophilia A and B patients with inhibitors for:
- Control and prevention of bleeding episodes
- Perioperative management
- Routine prophylaxis to prevent or reduce the frequency of
bleeding episodes.
FEIBA is not indicated for the treatment of bleeding episodes
resulting from coagulation factor deficiencies in the absence of
inhibitors to coagulation factor VIII or coagulation factor IX.
Detailed Important Risk Information for FEIBA [Anti-Inhibitor
Coagulant Complex]
WARNING: THROMBOEMBOLIC EVENTS
- Thromboembolic events have been reported during
post-marketing surveillance following infusion of FEIBA,
particularly following the administration of high doses and/or in
patients with thrombotic risk factors.
- Monitor patients receiving FEIBA for signs and symptoms of
thromboembolic events.
The use of FEIBA is contraindicated in patients with:
- Known anaphylactic or severe hypersensitivity reactions to
FEIBA or any of its components, including factors of the kinin
generating system
- Disseminated intravascular coagulation (DIC)
- Acute thrombosis or embolism (including myocardial
infarction)
Thromboembolic events (including venous thrombosis, pulmonary
embolism, myocardial infarction, and stroke) can occur with FEIBA,
particularly following the administration of high doses (above 200
units per kg per day) and/or in patients with thrombotic risk
factors.
Infusion of FEIBA should not exceed a dose of 100 units per kg
body weight every 6 hours and daily doses of 200 units per kg body
weight. Maximum injection or infusion rate must not exceed 2 units
per kg of body weight per minute. Monitor patients receiving more
than 100 units per kg of body weight of FEIBA for the development
of DIC, acute coronary ischemia and signs and symptoms of other
thromboembolic events. If clinical signs or symptoms occur, such as
chest pain or pressure, shortness of breath, altered consciousness,
vision, or speech, limb or abdomen swelling and/or pain,
discontinue the infusion and initiate appropriate diagnostic and
therapeutic measures.
Hypersensitivity and allergic reactions, including severe
anaphylactoid reactions, can occur following the infusion of FEIBA.
The symptoms include urticaria, angioedema, gastrointestinal
manifestations, bronchospasm, and hypotension. These reactions can
be severe and systemic (e.g., anaphylaxis with urticaria and
angioedema, bronchospasm, and circulatory shock). Other infusion
reactions, such as chills, pyrexia, and hypertension have also been
reported. If signs and symptoms of severe allergic reactions occur,
immediately discontinue administration of FEIBA and provide
appropriate supportive care.
Because FEIBA is made from human plasma it may carry a risk of
transmitting infectious agents, e.g., viruses, the variant
Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the
Creutzfeldt-Jakob disease (CJD) agent.
The most frequently reported adverse reactions observed in
>5% of subjects in the prophylaxis trial were anemia, diarrhea,
hemarthrosis, hepatitis B surface antibody positive, nausea, and
vomiting.
The serious adverse reactions seen with FEIBA are
hypersensitivity reactions and thromboembolic events, including
stroke, pulmonary embolism and deep vein thrombosis.
Use of antifibrinolytics within approximately 6 to 12 hours
after the administration of FEIBA is not recommended.
For FEIBA Full Prescribing Information,
visit http://www.shirecontent.com/PI/PDFs/FEIBA_USA_ENG.pdf
SHIRE and the Shire Logo are registered trademarks of Shire
Pharmaceutical Holdings Ireland Limited or its affiliates.
FEIBA is a registered trademark of Baxalta Incorporated, a
wholly owned, indirect subsidiary of Shire plc.
References
- WFH Inhibitors Working Group. "About Bleeding Disorders: What
are inhibitors?" World Federation of Hemophilia website.
http://www.wfh.org/en/page.aspx?pid=651 Accessed November 7, 2016.
- Wight J. Paisley S. "The
Epidemiology of Inhibitors in Haemophilia A: A Systematic Review."
Haemophilia 2003.
- Center for Disease Control and Prevention. "Inhibitors." CDC
website. https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html
Accessed November 30, 2016.
- Knappe S. et al. "Synergistic Effects of a Procoagulant
Bispecific Antibody and Rescue Therapies on Thrombin Generation- a
Potential Safety Risk." American Society of Hematology.
San Diego, California.
December 3-6, 2016. Available at:
http://www.bloodjournal.org/content/128/22/4952
- FEIBA Prescribing Information.
- Crea R. et al. "Four Decade Cumulative Review of
Thrombo-Embolic Events Reported with the Use of Activated
Prothrombin Complex Concentrate in Congenital Haemophilia."
American Society of Hematology. San
Diego, California. December 3-6,
2016. Available at:
http://www.bloodjournal.org/content/128/22/503
NOTES TO EDITORS
About Shire
Shire is the leading global biotechnology company focused on
serving people with rare diseases and other highly specialized
conditions. We strive to develop best-in-class products, many of
which are available in more than 100 countries, across core
therapeutic areas including Hematology, 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 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 with respect to
Shire's acquisition of NPS Pharmaceuticals, Inc., Dyax Corp.
("Dyax") or Baxalta Inc. ("Baxalta") 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 the 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;
- difficulties in integrating Dyax or Baxalta into Shire may lead
to the combined company not being able to realize the expected
operating efficiencies, cost savings, revenue enhancements,
synergies or other benefits at the time anticipated or at all;
and
- other risks and uncertainties detailed from time to time in
Shire's filings with the Securities and Exchange Commission,
including those risks outlined in "ITEM 1A: Risk Factors" in
Shire's Quarterly Report on Form 10-Q for the quarter
ended June 30, 2016.
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.
For further information, please contact:
Investor Relations
Sarah Elton-Farr - seltonfarr@shire.com
+44 1256 894157
Ian Karp - ikarp@shire.com
+1 781 482 9018
Robert Coates - rcoates@shire.com
+44 1256 894874
Media
Debbi Ford -debbi.ford@shire.com
+1 617 949 9083
Molly Poarch - molly.poarch@shire.com
+1 312 965 3413
SOURCE Shire plc