Decision solely based on published academic data endorsing the
benefit of Trisenox® as first
chemotherapy-free treatment for APL and marks important advancement for
patients in Europe
-
EU Commission grants an extension of indication to first line use
of Trisenox® in combination with retinoic acid
-
APL0406 study revealed a 99% overall survival rate in low to
intermediate risk APL patients with first line treatment with Trisenox®
in combination with retinoic acid1
JERUSALEM--(BUSINESS WIRE)--Nov. 21, 2016--
Teva Pharmaceutical Industries Ltd., (NYSE and TASE:TEVA) today
announced it has obtained approval from the European Commission for an
indication extension of Trisenox® (arsenic trioxide). This
marks an important advancement in treatment for Acute Promyelocytic
Leukemia (APL) patients in Europe, as it is the first time that a form
of acute leukemia can be effectively treated with a regimen that is
entirely chemotherapy-free. APL is a rare and aggressive type of acute
leukemia that can kill within hours or days if left untreated2.
Trisenox®, in combination with retinoic acid, has shown a 99%
overall survival rate with almost no relapses after more than four years
(50 months) of median follow-up1.
“Teva is committed to providing wider access to high-quality medicines
to ensure more people can benefit from the treatments they need. We’re
very pleased by this decision of the European Commission, and we look
forward to offering a chemotherapy-free treatment option for all newly
diagnosed APL patients,” said Rob Koremans, MD, President & CEO, Teva
Global Specialty Medicines.
The decision by the European Commission, which follows a positive
recommendation from the Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA) on October 13, grants
marketing authorization for first line use of Trisenox® in
the 28 countries of the European Union. The indication extension is for
newly diagnosed low to intermediate risk Acute Promyelocytic Leukemia
(APL) in combination with retinoic acid. Today’s announcement points to
a recognition by the European Commission that treating low to
intermediate risk APL with a chemo-free regimen of Trisenox®
plus retinoic acid can increase survival rates, dramatically reduce the
risk of relapse, and help avoid chemotherapy-related side effects, such
as the risk of life-threatening infections.
Welcoming the approval, Francesco Lo-Coco, Professor of Haematology and
Head of the Laboratory of Integrated Diagnosis of Oncohematologic
Diseases, Department of Biomedicine and Prevention, University of Rome
Tor Vergata, Italy said, “This approval by the European Commission is
good news for APL patients as we now have access to a cure for an acute
leukemia without using chemotherapy. Moreover, this decision is a very
positive endorsement by the European Commission, as it was made based
solely on published academic research and studies. From now on, APL
patients with non-high risk disease will have access to this
chemotherapy-free regimen of Trisenox® plus retinoic acid at
diagnosis, which has the potential to increase survival rates while
minimizing side effects associated with chemotherapy.”
In Europe, approximately 1,500 to 2,000 people are diagnosed with APL
each year3. APL, a life-threatening form of leukemia, can
cause uncontrollable bleeding leading rapidly to death if
left untreated2. The rapid progression of APL
leading to early mortality is a substantial problem, affecting up to 30%
of patients4. Rapid diagnosis and commencement of treatment
is essential to avoid early mortality2,5.
About Acute Promyelocytic Leukemia
Acute Promyelocytic Leukemia is a form of acute myeloid leukemia (AML),
a cancer of the blood-forming tissue (bone marrow). Approximately 5% to
10% of patients initially diagnosed with AML present with the aggressive
sub-type of the condition, APL6.
In normal bone marrow, hematopoietic stem cells produce red blood cells
(erythrocytes) that carry oxygen, white blood cells (leukocytes) that
protect the body from infection, and platelets (thrombocytes) that are
involved in blood clotting. In APL, immature white blood cells called
promyelocytes accumulate in the bone marrow. The overgrowth of
promyelocytes leads to a shortage of normal white and red blood cells
and platelets in the body, which causes many of the signs and symptoms
of the condition.
People with APL are especially susceptible to developing bruises, small
red dots under the skin (petechiae), nosebleeds, bleeding from the gums,
blood in the urine (hematuria), or excessive menstrual bleeding. The
most important lethal bleeding sites are pulmonary (35%) and
intracranial (65%)7. The abnormal bleeding and bruising occur
because leukemic blasts produce anticoagulant factors and substances are
released that cause excessive blood clotting, leading as a consequence
to a low number of platelets in the blood (thrombocytopenia). The low
number of red blood cells (anemia) can cause people with acute
promyelocytic leukemia to have pale skin (pallor) or excessive tiredness
(fatigue). In addition, affected individuals may heal slowly from
injuries or have frequent infections due to the decrease of normal white
blood cells that fight infection. Furthermore, the leukemic cells can
expand into the bones and joints, which may cause pain in those areas.
Other general signs and symptoms may occur as well, such as fever, loss
of appetite, and weight loss.
APL is generally diagnosed in much younger patients than in AML (the
median age is approximately mid-408,9 for APL patients and 67
for AML patients10), and can be diagnosed in patients of any
age.
About Trisenox®
On 5 March 2002, the European Commission granted approval for the
Marketing Authorization Application (MAA) for Trisenox®. The
authorization, which was valid throughout the European Union (EU), was
granted to treat patients with relapsed or refractory acute
promyelocytic leukemia (APL) and characterized by the presence of the
t(15;17) translocation and/or the presence of the Pro-Myelocytic
Leukaemia/Retinoic-Acid-Receptoralpha (PML/(RARα) gene. Trisenox®,
a targeted drug, degrades the PML- RARα fusion protein. Trisenox®
received marketing authorization in 2000 by the U.S. Food and Drug
Administration.
The marketing approval for Trisenox® was granted based on
results from a multicenter study in which 40 relapsed APL patients were
treated with Trisenox® 0.15 mg/kg until bone marrow remission
or a maximum of 60 days. Thirty-four patients (85 percent) achieved
complete remission after two cycles. When the results for these 40
patients were combined with those for the 12 patients in a pilot trial,
an overall response rate of 87 percent was observed11.
1mL of Trisenox® contains 1mg of arsenic trioxide. Trisenox®
is a concentrate for solution for infusion. It is a sterile, clear,
colorless, aqueous solution. Trisenox® must be administered
under the supervision of a physician who is experienced in the
management of acute leukaemias, and special monitoring procedures must
be followed.
Study Results
The APL0406 Intergroup GIMEMA-AMLSG-SAL study was a prospective,
randomized, multicenter, open-label, phase III non-inferiority study1.
Eligible patients were adults between 18 and 71 years of age with newly
diagnosed, genetically proven low- or intermediate-risk APL (WBC at
diagnosis ≤ 103 x 109/L). Overall, 276 patients
were randomly assigned to receive ATRA-ATO or ATRA-CHT between October
2007 and January 2013. Of 263 patients evaluable for response to
induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients
achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms,
respectively (P = .12). After a median follow-up of 40.6 months, the
event-free survival, cumulative incidence of relapse, and overall
survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms
were 97.3%v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P ,
.001, P = .0013, and P = .0073, respectively).
Post-induction events included two relapses and one death in CR in the
ATRA-ATO arm and two instances of molecular resistance after third
consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm.
Two patients in the ATRA-CHT arm developed a therapy-related myeloid
neoplasm.
References:
1. Journal of Clinical Oncology, July 11, 2016 as
10.1200/JCO.2016.67.1982.Improved Outcomes With Retinoic Acid and
Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in
Non–High-Risk Acute Promyelocytic Leukemia: Final Results of the
Randomized Italian-German APL0406 Trial. Professor Uwe Platzbecker et
al. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2016.67.1982
2. Coombs CC, et al. Blood Cancer J. 2015;5,e304.
3. Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O,
et al. Incidence of hematologic malignancies in Europe by morphologic
subtype: results of the HAEMACARE project. Blood 2010;116(19):3724-34.
4. Lehmann S, Ravn A, Carlsson L, et al. Continuing high early death
rate in acute promyelocytic leukemia: a population based report from the
Swedish Adult Acute Leukemia Registry. Leukemia 2011;25:1128–34
5. Lo-Coco F. Blood. 2011;118:1188-9
6. Cicconi L, Lo-Coco F. Ann Oncol. 2016;27:1847-81
7. De la Serna J, et al. Blood. 2008;111:3395-402
8. Howlader N, Noone AM, Krapcho M, et al, eds. SEER Cancer Statistics
Review, 1975-2012, National Cancer Institute. Bethesda, MD.
http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data
submission, posted to the SEER web site, April 2015. Accessed June 8,
2016.
9. Lo-Coco F, Cicconi L, Breccia M. Current standard treatment of adult
acute promyelocytic leukaemia. Br J Haematol. 2015.
doi.10.1111.bjh.13890.
10. National Cancer Institute SEER Stat Factsheet Acute Promyelocytic
Leukemia http://seer.cancer.gov/statfacts/html/amyl.html
accessed 16 Nov 2016
11. Soignet SL, et al. J Clin Oncol. 2001;19:3852-3860.
About Teva
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading
global pharmaceutical company that delivers high-quality,
patient-centric healthcare solutions used by millions of patients every
day. Headquartered in Israel, Teva is the world’s largest generic
medicines producer, leveraging its portfolio of more than 1,800
molecules to produce a wide range of generic products in nearly every
therapeutic area. In specialty medicines, Teva has a world-leading
position in innovative treatments for disorders of the central nervous
system, including pain, as well as a strong portfolio of respiratory
products. Teva integrates its generics and specialty capabilities in its
global research and development division to create new ways of
addressing unmet patient needs by combining drug development
capabilities with devices, services and technologies. Teva's net
revenues in 2015 were $19.7 billion. For more information, visit www.tevapharm.com.
Teva's Safe Harbor Statement under the U. S. Private Securities
Litigation Reform Act of 1995:
This release contains forward-looking statements, which are based on
management’s current beliefs and expectations and involve a number of
known and unknown risks and uncertainties that could cause our future
results, performance or achievements to differ significantly from the
results, performance or achievements expressed or implied by such
forward-looking statements. Important factors that could cause or
contribute to such differences include risks relating to: our ability to
develop and commercialize additional pharmaceutical products;
competition for our specialty products, especially Copaxone®
(which faces competition from orally-administered alternatives and a
generic version); our ability to integrate Allergan plc’s worldwide
generic pharmaceuticals business (“Actavis Generics”) and to realize the
anticipated benefits of the acquisition (and the timing of realizing
such benefits); the fact that following the consummation of the Actavis
Generics acquisition, we are dependent to a much larger extent than
previously on our generic pharmaceutical business; potential
restrictions on our ability to engage in additional transactions or
incur additional indebtedness as a result of the substantial amount of
debt incurred to finance the Actavis Generics acquisition; the fact that
for a period of time following the Actavis Generics acquisition, we will
have significantly less cash on hand than previously, which could
adversely affect our ability to grow; the possibility of material fines,
penalties and other sanctions and other adverse consequences arising out
of our ongoing FCPA investigations and related matters; our ability to
achieve expected results from investments in our pipeline of specialty
and other products; our ability to identify and successfully bid for
suitable acquisition targets or licensing opportunities, or to
consummate and integrate acquisitions; the extent to which any
manufacturing or quality control problems damage our reputation for
quality production and require costly remediation; increased government
scrutiny in both the U.S. and Europe of our patent settlement
agreements; our exposure to currency fluctuations and restrictions as
well as credit risks; the effectiveness of our patents, confidentiality
agreements and other measures to protect the intellectual property
rights of our specialty medicines; the effects of reforms in healthcare
regulation and pharmaceutical pricing, reimbursement and coverage;
competition for our generic products, both from other pharmaceutical
companies and as a result of increased governmental pricing pressures;
governmental investigations into sales and marketing practices,
particularly for our specialty pharmaceutical products; adverse effects
of political or economic instability, major hostilities or acts of
terrorism on our significant worldwide operations; interruptions in our
supply chain or problems with internal or third-party information
technology systems that adversely affect our complex manufacturing
processes; significant disruptions of our information technology systems
or breaches of our data security; competition for our specialty
pharmaceutical businesses from companies with greater resources and
capabilities; the impact of continuing consolidation of our distributors
and customers; decreased opportunities to obtain U.S. market exclusivity
for significant new generic products; potential liability in the U.S.,
Europe and other markets for sales of generic products prior to a final
resolution of outstanding patent litigation; our potential exposure to
product liability claims that are not covered by insurance; any failure
to recruit or retain key personnel, or to attract additional executive
and managerial talent; any failures to comply with complex Medicare and
Medicaid reporting and payment obligations; significant impairment
charges relating to intangible assets, goodwill and property, plant and
equipment; the effects of increased leverage and our resulting reliance
on access to the capital markets; potentially significant increases in
tax liabilities; the effect on our overall effective tax rate of the
termination or expiration of governmental programs or tax benefits, or
of a change in our business; variations in patent laws that may
adversely affect our ability to manufacture our products in the most
efficient manner; environmental risks; and other factors that are
discussed in our Annual Report on Form 20-F for the year ended December
31, 2015 and in our other filings with the U.S. Securities and Exchange
Commission (the "SEC"). Forward-looking statements speak only as of the
date on which they are made and we assume no obligation to update or
revise any forward-looking statements or other information, whether as a
result of new information, future events or otherwise.
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Source: Teva Pharmaceutical Industries Ltd.
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