CAMBRIDGE, Massachusetts,
February 23, 2017 /PRNewswire/ --
Results Served as Basis for Ongoing Phase 3
Trial
Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare
diseases, today announced the publication of results from the Phase
1b study of lanadelumab (SHP643;
formerly DX-2930) in the February 23,
2017 issue of the New England Journal of Medicine
(NEJM).
Lanadelumab is a subcutaneously administered, human monoclonal
antibody that specifically binds and inhibits plasma kallikrein,
and it is being investigated for the prevention of angioedema
attacks in patients with hereditary angioedema (HAE). HAE is a
rare, genetic disorder estimated to affect about 1 in 10,000 to 1
in 50,000 people worldwide.[1] The
condition results in recurrent, localized edema (swelling). The
areas of the body most commonly affected are the extremities,
gastrointestinal tract, and upper
airways.[2],[3]
"In this Phase 1b study, no serious adverse events or
discontinuations due to adverse events were observed at all doses
studied. Pre-specified efficacy analyses in patients with at least
2 attacks in the 3 months prior to enrolment demonstrated that from
day 8 to day 50, the administration of two doses of lanadelumab
(300 or 400 mg) 14 days apart, reduced the rate of attacks by 100%
and 88% respectively, when compared with placebo. In
addition, all subjects were attack-free in the 300 mg group and 82%
were attack-free in the 400 mg group, compared to 27% in the
placebo group," said Dr. Aleena
Banerji, Associate Professor, Massachusetts General
Hospital, Boston.
"The overall results of this study are encouraging; it should be
noted that while the duration of treatment was relatively short and
only a small number of patients were investigated, the results
supported further Phase 3 investigations, which are currently
ongoing," added Dr. Paula Busse,
Associate Professor, Mount Sinai Hospital, New York.
"Despite improvements in the management of HAE in recent years,
there is still a need for long-acting prophylactic treatment
options. At Shire we are proud of our history in HAE and ongoing
commitment to the clinical development of lanadelumab, an
investigational prophylactic therapy for this rare genetic
disease," said Philip J. Vickers,
Ph.D., Global Head of Research and Development at Shire.
The complete publication can be found at
nejm.org.[4] The main results were
previously presented at the American College of Allergy, Asthma,
and Immunology (ACAAI) Annual Scientific Meeting in 2015.
A pivotal Phase 3 trial evaluating the safety and efficacy of
lanadelumab as a long-acting prophylactic treatment for HAE is
currently underway.
With the clinical development of lanadelumab, Shire is building
on its legacy in HAE and as the world leader in rare diseases.
About the Study
(NCT02093923)[4]
The multicenter, randomized, double-blind, placebo-controlled,
multiple-ascending dose study enrolled a total of 37 patients
randomized to receive lanadelumab or placebo across four different
dosing groups of 30, 100, 300, or 400 mg. Each subject received two
doses of lanadelumab or placebo, separated by 14 days, and was
followed for 120 days post-dose. The primary objective of the study
was to assess the safety and tolerability of multiple subcutaneous
administrations of lanadelumab at different dose levels in HAE
patients. Secondary and tertiary objectives included
characterization of the pharmacokinetics and pharmacodynamics of
lanadelumab, evaluation of immunogenicity, and assessments of HAE
attack frequency and use of acute attack therapy.
There were no serious adverse events or discontinuations due to
adverse events reported in patients treated with lanadelumab. A
total of 29% of the patients who received lanadelumab and 38% of
those who received placebo had an adverse event that was considered
by trial investigators, who were unaware of the trial-group
assignments, to be treatment-related. The most common
treatment-related adverse events were injection site pain (25%
lanadelumab, 23% placebo) and headache (8% lanadelumab, 15%
placebo).
In HAE patients, the pharmacokinetic profile of lanadelumab is
linear, dose-dependent, and exhibits a half-life of approximately
14 days, typical of a human monoclonal antibody. The
pharmacodynamic profile of lanadelumab was assessed by plasma
levels of cleaved high molecular weight kininogen (cHMWK).
Pharmacodynamic results confirm plasma kallikrein inhibition in a
dose and time-dependent manner, and suggest doses of 300 mg or
greater have the potential to normalize cHMWK levels based on
levels of cHMWK approaching that observed in healthy
subjects.
About HAE
HAE is a rare genetic disease characterized by recurrent and
spontaneous episodes of swelling (edema), typically affecting the
extremities, abdomen, face, throat and/or genitourinary
tract.[2],[3]
Swelling of the throat can be life-threatening due to
asphyxiation.[5]-[7]
In most cases, the disease is caused by a deficiency of functional
C1-esterase inhibitor. This deficiency eventually results in
excessive bradykinin production. Bradykinin is a vasodilator
responsible for the characteristic symptoms of localized swelling,
inflammation, and pain in
HAE.[8]
About Lanadelumab
Unopposed activation of the kallikrein-kinin cascade leads to
uncontrolled generation of plasma kallikrein, resulting in
excessive bradykinin production.
Lanadelumab is an investigational human monoclonal antibody that
specifically binds and inhibits plasma kallikrein, and it is being
developed for the prevention of angioedema attacks in adult
patients with HAE. Lanadelumab is formulated for subcutaneous
administration with a half-life of approximately 14 days in
patients with HAE.[4]
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;
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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 September 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.
References
- Longhurst, Hilary. Hereditary Angioedema: Causes,
Manifestations and Treatment. British Journal of Hospital Medicine.
2006; 67:654-57
- Cicardi M, et al. Classification, diagnosis and approach to
treatment for angioedema: consensus report from the Hereditary
Angioedema International Working Group. Allergy.
2014;69(5):602-16
- Bork K, et al. Hereditary angioedema: New findings concerning
symptoms, affected organs, and course. Am J Med. 2006; 119(3):
267-74
- Banerji A, et al. Inhibiting Plasma Kallikrein for Hereditary
Angioedema Prophylaxis. N Engl J Med 2017;376:717-728
- Bork K, et al. Asphyxiation by laryngeal edema in patients with
hereditary angioedema. Mayo Clin
Proc. 2000; 75: 349-354
- Bork K, et al. Clinical studies of sudden upper airway
obstruction in patients with hereditary angioedema due to C1
esterase inhibitor deficiency. Arch Intern Med. 2003; 163:
1229-1235
- Bork K, et al. Fatal laryngeal attacks and mortality in
hereditary angioedema due to C1-INH deficiency. J Allergy Clin
Immunol 2012;130:692-7
- Kaplan AP and Joseph K. The bradykinin-forming cascade and its
role in hereditary angioedema. Ann Allergy Asthma Immunol
2010;104:193-204.
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
+41-79-630-8619
Charles Catalano
ccatalano0@shire.com
+1-513-575-6978
SOURCE Shire plc