Market Overview

Teva Announces Top-Line Results from Phase III Studies of Subcutaneously Administered Reslizumab in Patients with Severe Eosinophilic Asthma

Share:

Teva Pharmaceutical Industries Ltd., (NYSE and TASE: TEVA) today
announced that a Phase III registration study evaluating subcutaneously
administered reslizumab (110 mg) in a pre-filled syringe did not meet
its primary endpoint of significantly reducing the frequency of clinical
asthma exacerbations (CAEs) in patients with uncontrolled asthma and
elevated blood eosinophils >300/mcL. A Phase III claim-support study
evaluating subcutaneously administered reslizumab in patients with oral
corticosteroid (OCS)-dependent asthma did not meet its primary endpoint
of reduction in daily OCS dose.

"We are disappointed that these trials of the reslizumab formulation
administered subcutaneously at a fixed-dose of 110 mg did not meet their
primary endpoints. However, these results reinforce the role of
eosinophils in severe asthma disease biology and the importance of
defining the right blood eosinophil cutoff point for patient selection.
We continue to see the positive impact of the intravenous formulation as
a clinically effective 3mg/kg weight-based dosing option in patients
with asthma and elevated blood eosinophils who are inadequately
controlled on standard-of-care therapy," said Tushar Shah, MD, Senior
Vice President, Specialty Clinical Development and Medical Affairs at
Teva.

In the registration study, a pre-specified a priori-powered subgroup
analysis of 80% of the total randomized severe asthma patient population
with baseline blood eosinophil count of ≥ 400/mcL showed significant
reduction in CAE risk (p <0.025). This patient population is similar to
those studied in the Phase III clinical trials for CINQAIR®/CINQAERO®
(reslizumab) injection, the currently approved intravenous formulation,
which also used a blood eosinophil count of ≥ 400/mcL.

Teva will review the full data to determine next steps.

No new safety concerns to the known safety profile of reslizumab were
identified in review of the data from these studies and no cases of
anaphylaxis related to reslizumab were reported.

About the Studies

Study NCT02452190 was a registration Phase III, 52-week,
double-blind, placebo-controlled study designed to evaluate the efficacy
and safety of reslizumab administered subcutaneously in 468 patients
with uncontrolled asthma and elevated blood eosinophils. Its primary
objective was to demonstrate the efficacy of reslizumab (110 mg) fixed,
subcutaneous dosing every 4 weeks, as assessed by the reduction in
frequency of clinical asthma exacerbations (CAEs). For further details
on the study, please visit: https://clinicaltrials.gov/ct2/show/NCT02452190?term=NCT02452190&cntry1=NA%3AUS&rank=1

Study NCT02501629 was a claim-support Phase III, 24-week,
double-blind, placebo-controlled, parallel-group study to evaluate the
efficacy and safety of reslizumab administered subcutaneously in 177
patients with oral corticosteroid (OCS) dependent asthma and elevated
blood eosinophils. Its primary objective was to demonstrate the efficacy
of reslizumab (110 mg) fixed, subcutaneous dosing every 4 weeks, as
assessed by reduction in daily OCS dose compared with baseline. For
further details on the study, please visit: https://clinicaltrials.gov/ct2/show/NCT02501629?term=reslizumab&cntry1=NA%3AUS&draw=2&rank=10

About CINQAIR®/CINQAERO®
(reslizumab) injection for intravenous use

CINQAIR (reslizumab) Injection is an interleukin-5 antagonist monoclonal
antibody (IgG4 kappa) indicated for add-on maintenance treatment of
patients with severe asthma aged 18 years and older, and with an
eosinophilic phenotype.

Limitations of Use: CINQAIR is not
indicated for:

  • treatment of other eosinophilic conditions
  • relief of acute bronchospasm or status asthmaticus

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS

  • Anaphylaxis has been observed with CINQAIR infusion in 0.3% of
    patients in placebo-controlled clinical studies. Anaphylaxis was
    reported as early as the second dose of CINQAIR.
  • Anaphylaxis can be life-threatening. Patients should be observed
    for an appropriate period of time after CINQAIR administration by a
    healthcare professional prepared to manage anaphylaxis. Discontinue
    CINQAIR immediately if the patient experiences signs or symptoms of
    anaphylaxis.

CONTRAINDICATIONS

  • CINQAIR is contraindicated in patients who have known hypersensitivity
    to reslizumab or any of its excipients.

WARNINGS AND PRECAUTIONS

  • Acute Asthma Symptoms or Deteriorating Disease: CINQAIR should
    not be used to treat acute asthma symptoms or acute exacerbations. Do
    not use CINQAIR to treat acute bronchospasm or status asthmaticus.
    Patients should seek medical advice if their asthma remains
    uncontrolled or worsens after initiation of treatment with CINQAIR.
  • Malignancy: In placebo-controlled clinical studies, 6/1028
    (0.6%) patients receiving 3 mg/kg CINQAIR had at least 1 malignant
    neoplasm reported compared to 2/730 (0.3%) patients in the placebo
    group. The observed malignancies in CINQAIR-treated patients were
    diverse in nature and without clustering of any particular tissue
    type. The majority of malignancies were diagnosed within less than six
    months of exposure to CINQAIR.
  • Reduction of Corticosteroid Dosage: No clinical studies have
    been conducted to assess reduction of maintenance corticosteroid
    dosages following administration of CINQAIR. Do not discontinue
    systemic or inhaled corticosteroids abruptly upon initiation of
    therapy with CINQAIR. Reductions in corticosteroid dose, if
    appropriate, should be gradual and performed under the supervision of
    a physician. Reduction in corticosteroid dose may be associated with
    systemic withdrawal symptoms and/or unmask conditions previously
    suppressed by systemic corticosteroid therapy.
  • Parasitic (Helminth) Infection: Eosinophils may be involved in
    the immunological response to some helminth infections. Treat patients
    with pre-existing helminth infections before initiating CINQAIR. If
    patients become infected while receiving treatment with CINQAIR and do
    not respond to anti-helminth treatment, discontinue treatment with
    CINQAIR until infection resolves.

ADVERSE REACTIONS

  • Adverse reactions that occurred at ≥2% incidence and more commonly
    than in the placebo group included 1 event: oropharyngeal pain (2.6%
    vs. 2.2%).
  • Elevated baseline creatine phosphokinase (CPK) was more frequent in
    patients randomized to CINQAIR (14%) versus placebo (9%). Transient
    CPK elevations in patients with normal baseline CPK values were
    observed more frequently with CINQAIR (20%) versus placebo (18%)
    during routine laboratory assessments.
  • Myalgia was reported in 1% (10/1028) of patients in the CINQAIR 3
    mg/kg group compared to 0.5% (4/730) of patients in the placebo group.
  • Immunogenicity: In placebo-controlled studies, a treatment-emergent
    anti-reslizumab antibody response developed in 53/983 (5.4%) of
    CINQAIR-treated patients (3 mg/kg). The antibody responses were of low
    titer and often transient. There was no detectable impact of the
    antibodies on the clinical pharmacokinetics, pharmacodynamics,
    clinical efficacy, and safety of CINQAIR.

Please
click here for Full Prescribing Information

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 approximately 200 million
patients in over 60 markets 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 the
world-leading innovative treatment for multiple sclerosis as well as
late-stage development programs for other disorders of the central
nervous system, including movement disorders, migraine, pain and
neurodegenerative conditions, as well as a broad portfolio of
respiratory products. Teva is leveraging its generics and specialty
capabilities in order to seek new ways of addressing unmet patient needs
by combining drug development with devices, services and technologies.
Teva's net revenues in 2016 were $21.9 billion. For more information,
visit www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995
regarding Subcutaneously Administered Reslizumab, which are based on
management's current beliefs and expectations and are subject to
substantial risks and uncertainties, both known and unknown, that could
cause our future results, performance or achievements to differ
significantly from that expressed or implied by such forward-looking
statements. Important factors that could cause or contribute to such
differences include risks relating to:

  • the uncertainty of commercial success of reslizumab;
  • our specialty medicines business, including: competition for our
    specialty products, especially Copaxone
    ®, our
    leading medicine, which faces competition from existing and potential
    additional generic versions and orally-administered alternatives; our
    ability to achieve expected results from investments in our product
    pipeline; competition from companies with greater resources and
    capabilities; and the effectiveness of our patents and other measures
    to protect our intellectual property rights;
  • our business and operations in general, including: uncertainties
    relating to the potential success and our ability to effectively
    execute a restructuring plan; uncertainties relating to the potential
    benefits and success of our new organizational structure and recent
    senior management changes; our ability to develop and commercialize
    additional pharmaceutical products; manufacturing or quality control
    problems, which may damage our reputation for quality production and
    require costly remediation; interruptions in our supply chain;
    disruptions of our or third party information technology systems or
    breaches of our data security; the restructuring of our manufacturing
    network, including potential related labor unrest; the impact of
    continuing consolidation of our distributors and customers; and
    variations in patent laws that may adversely affect our ability to
    manufacture our products;
    our ability to consummate
    dispositions on terms acceptable to us; adverse effects of political
    or economic instability, major hostilities or terrorism on our
    significant worldwide operations; and our ability to successfully bid
    for suitable acquisition targets or licensing opportunities, or to
    consummate and integrate acquisitions;
  • compliance, regulatory and litigation matters, including: costs and
    delays resulting from the extensive governmental regulation to which
    we are subject; the effects of reforms in healthcare regulation and
    reductions in pharmaceutical pricing, reimbursement and coverage;
    potential additional adverse consequences following our resolution
    with the U.S. government of our FCPA investigation; governmental
    investigations into sales and marketing practices; potential liability
    for sales of generic products prior to a final resolution of
    outstanding patent litigation; product liability claims; increased
    government scrutiny of our patent settlement agreements; failure to
    comply with complex Medicare and Medicaid reporting and payment
    obligations; and environmental risks;
    and other factors
    discussed in our Annual Report on Form 20-F for the year
    ended December 31, 2016 ("Annual Report"), including in the section
    captioned "Risk Factors," and in our other filings with the U.S.
    Securities and Exchange Commission, which are available at
    www.sec.gov
    and
    www.tevapharm.com.
    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 contained herein,
    whether as a result of new information, future events or otherwise.

    You are cautioned not to put undue reliance on these
    forward-looking statements.

View Comments and Join the Discussion!