Teva’s Asthma Drug Flunks Two Phase III Trials

JERUSALEM--(BUSINESS WIRE)-- Teva Pharmaceuticals (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.

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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.

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