Teva Receives Positive Opinion from European Medicines Agency to Extend Indication of Trisenox®

- October 17th, 2016

Teva Pharmaceutical Industries today announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending an indication extension of Trisenox® (arsenic trioxide).

Teva Pharmaceutical Industries Ltd., (NYSE and TASE:TEVA) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an indication extension of Trisenox® (arsenic trioxide). The indication extension is for use in newly diagnosed low to intermediate risk Acute Promyelocytic Leukemia (APL) in combination with retinoic acid. Trisenox®, in combination with retinoic acid, has shown a very high overall survival rate with almost no relapses
after more than four years (50 months) of median follow-up. If the European Commission approves this label extension, it would mark the first time that a form of acute leukemia can be effectively treated with a regimen that is entirely chemotherapy-free.
APL is a life-threatening type of leukemia as it can cause
uncontrollable bleeding and can kill within hours or days if left
untreated. In Europe, approximately 1,500 to 2,000 people are diagnosed
with APL each year. In light of its rarity, and because most cases
present with low blood cell count and low leukemic cells in the blood,
diagnosis can be difficult. However, the rapid progression of APL
leading to early mortality is a substantial problem, affecting up to 30%
of patients. Rapid diagnosis and commencement of treatment is essential
to avoid early mortality. Trisenox® is currently indicated
for second line treatment of patients, who have not responded to
treatment with retinoids and chemotherapy, or when their disease has
returned after this type of treatment.
Commenting on the announcement, 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 CHMP opinion is very
encouraging. Considering it was based on existing published academic
data only, this opinion points to a recognition by the EMA that treating
low to intermediate risk APL with a chemo-free regimen of Trisenox®
plus retinoic acid can increase survival rates and dramatically reduce
the risk of relapse and chemotherapy-related side effects in patients
suffering from this rare and aggressive form of leukemia. In particular,
avoiding the risk of life-threatening infection and that of developing
secondary leukemias due to chemotherapy is a great gain for patients.
The success of this regimen represents a major breakthrough and a
paradigm of targeted therapy in oncology and medicine. This is therefore
good news, not only for APL patients, but also for the whole medical
The CHMP positive opinion is a formal recommendation to grant marketing
authorization for an extended indication for first line treatment for
Trisenox®. The recommendation will now be reviewed by the
European Commission, which has authority to approve medicines for use in
the 28 countries of the European Union along with Norway, Liechtenstein
and Iceland. A final decision by the European Commission is expected by
the end of the year.
In commenting on the CHMP positive opinion, Rob Koremans, President &
CEO, Teva Global Specialty Medicines said, “As a company committed to
providing medicines and solutions that really make a difference in
patients’ lives, we’re pleased to reach this important milestone, and
hope soon to be able to offer a chemotherapy-free treatment regimen for
APL patients at the point of diagnosis. Recognizing the high unmet
patient need in this orphan disease, we’ve put everything in place to
obtain the label extension for this life-saving treatment. We look
forward to receiving an approval from the European Commission for
Trisenox® as a first line treatment.”
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 10% to
15% of patients initially diagnosed with AML present with the aggressive
sub-type of the condition, APL.
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
abnormal bleeding and bruising occur because substances are released
that cause excessive blood clotting, and as a consequence lead 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 40 for APL patients and 70 for AML
patients), 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
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 observed.
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 study.
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,
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
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 amounted to $19.7 billion. For more information, visit
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.

Leave a Reply