DUBLIN, October 18, 2016 /PRNewswire/ --
ONIVYDE, in combination with
5-fluorouracil (5-FU) and leucovorin (LV), is the first and
only treatment approved for this patient population
based on pivotal Phase 3 data (NAPOLI-1) showing increased overall
survival[i],[ii]
Shire plc (LSE: SHP, NASDAQ: SHPG) announced that the European
Commission (EC) has granted Marketing Authorization of
ONIVYDE® (pegylated liposomal irinotecan hydrochloride
trihydrate), also known as nal-IRI or MM-398, for the treatment of
metastatic adenocarcinoma of the pancreas, in combination with
5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who
have progressed following gemcitabine-based therapy. ONIVYDE is the
first and only approved treatment option for this patient
population.
With this approval, Shire is authorized to market ONIVYDE in the
28 Member States of the European Union (EU), as well as in
Iceland, Liechtenstein and Norway. ONIVYDE was previously approved in the
U.S. by the Food and Drug Administration (FDA), in October 2015.
"As the only treatment for metastatic pancreatic cancer
following gemcitabine-based therapy that may improve patient
survival, ONIVYDE is the first innovation that offers the potential
to improve outcomes for this challenging patient population," said
Philip J. Vickers, Ph.D., Global
Head of Research and Development at Shire. "The approval of ONIVYDE
marks a significant step forward in Shire's focus to develop and
commercialize treatments that represent the most promising science
in oncology."
Pancreatic cancer is the fourth leading cause of cancer death in
the region[iii] and there are limited treatment options
available.[iv] In September
2015, the European Society of Medical Oncology (ESMO) stated
that use of MM-398 (ONIVYDE) when available in all countries, may
be the best option for patients following gemcitabine-based
therapy.[v] Gemcitabine-based therapy is commonly used
as a first-line treatment for patients with metastatic disease or
locally advanced disease that cannot be treated with surgery, or as
adjuvant
therapy.[vi]
"The burden of pancreatic cancer for patients, their families
and healthcare providers is profound and the treatment options
available, especially to those with metastatic disease, have not
substantially evolved for decades," said Alfredo Carrato, M.D., Professor of Medical
Oncology at Alcala University and Director of the Medical Oncology
Department at Ramon y Cajal University Hospital in Madrid, Spain. "With the approval of ONIVYDE,
we have the first and only treatment approved for metastatic
adenocarcinoma following gemcitabine-based therapy, and an option
that may improve patient survival. This is an important advance for
the field of oncology and the lives of those impacted by pancreatic
cancer."
The Marketing Authorization is based on the data from the
pivotal, Phase 3 NAPOLI-1 study that demonstrated ONIVYDE combined
with 5-FU/LV significantly improved overall survival (OS) (primary
endpoint), as well as progression-free survival (PFS) and objective
response rate (ORR) relative to the 5-FU/LV control arm (secondary
endpoints). In the trial, the most common Grade 3 or higher adverse
events with greater than five percent difference in patients
receiving ONIVYDE and 5-FU/LV, versus 5-FU/LV alone, were
neutropenia, fatigue, diarrhoea, and
vomiting.[ii]
About Pancreatic Cancer
Pancreatic cancer is a significantly underserved disease in
Europe and is almost always
fatal.[vi] At the time of diagnosis, more than 80
percent of people diagnosed with pancreatic cancer have metastatic
disease or locally advanced disease that cannot be removed with
surgery.[vii] The disease has a median five-year
survival rate of about 5
percent,[v] and an overall median
survival of typically less than a year, as supported by real-world
European systematic
review.[vi] The only
curative treatment for pancreatic cancer is surgical resection in
the primary stage, which can improve five-year survival to 10
percent.[viii]
The signs and symptoms of pancreatic cancer are non-specific
(common presenting symptoms include jaundice, abdominal pain,
weight loss, steatorrhoea, and new-onset
diabetes)[v] and may not appear
until the disease has spread locally or
metastasized.[vii] Therefore, most
patients are not candidates for surgery upon
diagnosis.[vii]
Even though it accounts for less than three percent of all
cancer cases,[ix] pancreatic cancer is the seventh
leading cause of cancer death worldwide,[x] and the
fourth in Europe.[iv]
Worldwide, pancreatic cancer prognosis is typically poor, with an
estimated 337,900 new cases and 330,400 deaths each
year.[xi]
About ONIVYDE (nal-IRI)
ONIVYDE is a first-of-its-kind formulation (encapsulation) of
irinotecan in a long-circulating liposomal form designed to improve
delivery of length of tumor exposure to irinotecan and its active
metabolite SN-38. Studies have suggested that encapsulation helps
to improve delivery of irinotecan to tumors, such as metastatic
pancreatic cancer.[xii]
In the pivotal Phase 3 NAPOLI-1 study, ONIVYDE demonstrated
significantly improved overall survival in adult patients with
metastatic ADENOCARCINOMA of the pancreas who have progressed
following gemcitabine-based
therapy.[ii] Gemcitabine, both as
monotherapy as well as in combination, is commonly used in the
first-line treatment of locally advanced and/or metastatic
pancreatic adenocarcinoma, as well as in the adjuvant (treatment
after surgery) and neo-adjuvant (treatment before surgery)
settings.[ii]
Shire is responsible for the development and commercialization
of ONIVYDE outside of the United
States and Taiwan under an
exclusive licensing agreement with Merrimack Pharmaceuticals, Inc.
(NASDAQ: MACK). Merrimack markets ONIVYDE in the United States after having received US
Food and Drug Administration (FDA) approval in October 2015 for the treatment of patients with
metastatic adenocarcinoma of the pancreas who have progressed
following treatment with gemcitabine-based therapy. ONIVYDE product
license was granted in Taiwan in
March 2016, where PharmaEngine holds
the commercialization rights.
About NAPOLI-1[ii]
NAPOLI-1 is the first global,
randomized open-label Phase 3 trial to show extended overall
survival in metastatic pancreatic adenocarcinoma after
gemcitabine-based therapy through treatment with ONIVYDE combined
with 5-FU and LV. NAPOLI-1 is the
largest Phase 3 study in this setting to date showing overall
survival benefit. Patients were enrolled at 76 sites in 14
countries across North America,
Europe, Asia, South
America, and Australia. The
study evaluated ONIVYDE
(80mg/m[2]) in combination with
5-FU/LV administered intravenously every two weeks and as a
monotherapy (120 mg/m[2])
administered every three weeks. Each ONIVYDE containing arm was
compared to a control arm of 5-FU/LV.
NAPOLI-1 met the following
primary and secondary endpoints by demonstrating that ONIVYDE
combined with 5-FU/LV significantly improved OS, progression-free
survival (PFS) and objective response (OR) compared to 5-FU/LV
alone in patients with metastatic pancreatic
cancer.[i] ONIVYDE plus 5-FU/LV
demonstrated a significant increase in median overall survival
versus 5-FU/LV alone: 6.1 months vs 4.2 months (based on a
non-stratified hazard ratio [HR] of 0.67; 95% CI 0.49-0.92,
p=0.012).[i],[
ii]
Grade 3 or 4 adverse events that occurred most frequently in the
117 patients assigned ONIVYDE plus 5-FU/LV were neutropenia (32
[27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16
[14%]). [ii]
Important Safety Information
The most common adverse reactions (incidence ≥20 percent) seen
with ONIVYDE in combination with 5-FU/LV were: diarrhoea, nausea,
vomiting, decreased appetite, neutropenia, fatigue, asthenia,
anaemia, stomatitis, and
pyrexia.[i] Early-onset (within 1
day of treatment) diarrhoea occurred in 30 percent of patients on
ONIVYDE combined with 5-FU/LV and was usually
transient.[i] Early-onset
diarrhoea was accompanied by cholinergic symptoms in 3.4 percent of
patients taking ONIVYDE in combination with 5-FU/LV.
[i] Median time to late-onset
diarrhoea was 8 days following the ONIVYDE
dose.[i] Of patients taking
ONIVYDE combined with 5-FU/LV, 11 percent of patients discontinued
treatment.[i]
ONIVYDE is a registered trademark of Merrimack Pharmaceuticals,
Inc. (NASDAQ: MACK), and used under license.
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.
i. SMPC
ii. Wang-Gillam A, et al. Nanoliposomal irinotecan with
fluorouracil and folinic acid in metastatic pancreatic cancer after
previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label,
phase 3 trial. The Lancet. 2016; 387(10018):545-557.
iii. Malvezzi M, Bertuccio P, Levi F, et al. European cancer
mortality predictions for the year. Ann Oncol. 2014;
25:1650-1656.
iv. Sclafani F, Iyer R, Cunningham D, Starling N. Management of
metastatic pancreatic cancer: Current treatment options and
potential new therapeutic targets. Critical Reviews in
Oncology/Hematology. 2015; (95) 318-336.
v. Ducreux M, Cuhna A, Caramella C, et al. Cancer of the
pancreas: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol. 2015; 26(5): 56-68.
vi. Carrato A, Falcone A, Ducreux M, et al. A Systematic Review
of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality
of Life and Costs. J Gastrointest Canc. 2015; 46: 201-211.
vii. Walker EJ and Ko AH. Beyond first-line chemotherapy for
advanced pancreatic cancer: An expanding array of therapeutic
options? World J Gastroenterol, 2014; 20(9): 2224-36.
viii. Jones OP, Melling JD, and Ghaneh P. Adjuvant therapy in
pancreatic cancer. World J Gastroenterol, 2014; 20: 14733-46.
ix. Worldwide data. World Cancer Research Fund Website.
http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/pancreatic-cancer-statistics
. Accessed March 8, 2016.
x. Pancreatic cancer statistics. World Cancer Research Fund
International. http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/pancreatic-cancer-statistics
. Accessed October 17, 2016
xi. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S,
Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence
and Mortality Worldwide: IARC CancerBase No. 11 [Internet].
Lyon, France: International Agency
for Research on Cancer; 2014. Available
from: http://globocan.iarc.fr , accessed on 10/17/2016.
xii. Ko AH, et al. A multinational phase 2 study of
nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients
with gemcitabine-refractory metastatic pancreatic cancer. British
Journal of Cancer. 2013; 109, 920-925
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
Deborah Hibbett, dhibbett@shire.com
, +41-7996-18464
Kelly Schlemm,
kelly.schlemm@shire.com, +1-617-588-8358