Teva Oncology Release: Omacetaxine Mepesuccinate Shows Activity in Chronic Myeloid Leukemia Patients Who Have Become Resistant to or Intolerant of Prior Tyrosine Kinase Inhibitor (TKls) (1,2,3)

NORTH WALES, Pa., June 1, 2012 /PRNewswire/ -- Teva Oncology presented two secondary analyses today featuring omacetaxine mepesuccinate, an investigational, first-in-class cephalotaxine that functions as a protein synthesis inhibitor at the American Society of Clinical Oncology Annual Meeting, June 1-5, 2012, Chicago. These analyses were derived from data that was submitted to the US Food and Drug Administration as part of a new drug application (NDA) and was recently accepted for review.(4)

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Research has shown that the use of second-generation TKI treatment after failure of two TKIs may induce responses, but these are usually not lasting except in some chronic phase patients, and new treatment options are needed after these failures.(5) Omacetaxine mepesuccinate has a different mechanism of action from TKIs and has shown activity in CML patients who have become resistant or intolerant to prior TKIs.

“For patients who have failed prior TKI therapies, and currently have limited treatment options beyond the third-line setting, a treatment with a different mechanism of action may be an option,” said Jorge Cortes, M.D., Chair, CML Section, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Featured data at this year’s ASCO meeting will include results from the following analyses:

• “Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) Resistant/Intolerant to Two or Three Approved Tyrosine Kinase Inhibitors (TKIs)(1)^”
  • AP and CP CML patients (n = 122) who were resistant to/intolerant of TKI therapies responded to omacetaxine mepesuccinate therapy whether they had received two or all three approved prior TKI therapies.(1)
  • Median survival was 30.1 months for 2-TKI CP patients and not reached for 3-TKI CP patients and 12.0 and 24.6 for AP patients, respectively.(1)
  • Major cytogenetic response, defined as a reduction in the percentage of cells expressing the Philadelphia Chromosome to 35% or less in a CML patient(6), was achieved by a statistically significant proportion of CP patients, (12/45 patients [27%] of the 2-TKI group; 4/36 patients [11%] of the 3-TKI group). Major hematologic response was achieved by a statistically significant proportion of AP patients, (6/17 patients [35%] of the 2-TKI group; 5/24 patients [21%] of the 3-TKI group).(1)
  • Treatment-related grade 3/4 adverse events (AEs) occurred in 52 (84%) patients in the 2-TKI group and 42 (70%) in the 3-TKI group (most common: thrombocytopenia [71%, 48%]).(1)
• “Omacetaxine Mepesuccinate in Chronic Phase (CP) Chronic Myeloid Leukemia (CML) In Patients Resistant, Intolerant, or Both to Two or More Tyrosine Kinase Inhibitors (TKIs)(2)”
  • CP CML patients who were resistant to, intolerant of, or resistant and intolerant of TKI therapies responded to omacetaxine mepesuccinate therapy.(2)
  • Median overall survival in months were 33.9 in resistant patients, not reached in intolerant patients, and 25.0 in those patients both resistant and intolerant.(2)
  • Major cytogenetic response, defined as a reduction in the percentage of cells expressing the Philadelphia Chromosome to 35% or less in a CML patient, was achieved by a statistically significant proportion of CP patients(6), (13/69 or 19% of resistant patients, 2/7 or 29% of intolerant patients and 1/5 or 20% of those both resistant and intolerant).(2)
  • Of the 66 (81%) patients with treatment-related grade 3/4 adverse events (AEs), the most common were thrombocytopenia, and neutropenia (44 thrombocytopenia and 32 neutropenia in resistant patients, 6 and 4 in intolerant patients, and 4 and 1 in resistant and intolerant patients).(2)

Platform presentation/session details:

Friday, June 1, Viewing time: 1:00-5:00 pm CT, Discussion time: 4:30-5:30 pm CT

• [6513] Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) Resistant/Intolerant to Two or Three Approved Tyrosine Kinase Inhibitors (TKIs) (Poster Discussion Session: Leukemia, Myelodysplasia, and Transplantation, Jeffrey H. Lipton, MD, PhD; Hagop M. Kantarjian, MD; Franck E. Nicolini, MD, PhD; Meir Wetzler, MD; Luke Akard, MD; Michele Baccarani, MD; Adam Craig, MD, PhD; Nisha Nanda, PhD; Peter Brown, DPhil; Jorge Cortes, MD)

Monday, June 4, 1:15-5:15 pm CT

• [6596] Omacetaxine Mepesuccinate in Chronic Phase (CP) Chronic Myeloid Leukemia (CML) In Patients Resistant, Intolerant, or Both to Two or More Tyrosine Kinase Inhibitors (TKIs) (General Poster Session: Leukemia, Myelodysplasia, and Transplantation, Luke Akard, MD; Hagop M. Kantarjian, MD; Franck E. Nicolini, MD, PhD; Meir Wetzler, MD; Jeffrey H. Lipton, MD, PhD; Michele Baccarani, MD; Adam Craig, MD, PhD^;Nisha Nanda, PhD; Peter Brown, DPhil; Jorge Cortes, MD)

ABOUT OMACETAXINE MEPESUCCINATE(4)
Omacetaxine mepesuccinate is an investigational first-in-class cephalotaxine that functions as a protein synthesis inhibitor, meaning that it may slow or stop cell growth by disrupting the part of the process involved in creating new cell proteins.

Omacetaxine mepesuccinate has two anti-leukemic actions: it reduces levels of oncoproteins, or proteins related to tumor cell growth, including the Bcr-Abl oncoprotein associated with CML, and it induces apoptosis, or self-destruction, in leukemic stem cells. Both actions may prevent the first steps in the process of protein reproduction essential for cell growth.

Omacetaxine mepesuccinate binds to the Bcr-Abl hybrid gene present in CML and is a different mechanism of action than TKIs.

ABOUT CML
Chronic myeloid leukemia (CML) (also called chronic myelogenous leukemia, chronic myelocytic leukemia or chronic granulocytic leukemia) is one of four main types of leukemia and is a cancer of the blood and bone marrow.(7) In CML, part of the DNA from one chromosome translocates with another chromosome, forming The Philadelphia Chromosome.(7) The Philadelphia Chromosome contains the Bcr-Abl gene, which results in the bone marrow’s making an enzyme called tyrosine kinase that causes too many stem cells to develop into white blood cells (granulocytes or blasts).(7) The American Cancer Society estimates that in 2012, there will be 5,430 new cases of CML diagnosed in the United States, and 610 people will die from the disease.(8)

About Teva Oncology
Teva Oncology is the U.S.-based branded oncology division of Teva Pharmaceutical Industries Ltd., formerly known as Cephalon Oncology. The portfolio currently includes drugs to treat leukemia, and iNHL and CLL plus a robust pipeline and multiple late-stage oncology compounds across cancer therapeutics and supportive care.

Teva’s Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements 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 successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which we may obtain U.S. market exclusivity for certain of our new generic products and regulatory changes that may prevent us from utilizing exclusivity periods, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic version of Protonix(R), the extent to which any manufacturing or quality control problems damage our reputation for high quality production, the effects of competition on sales of our innovative products, especially Copaxone(R) (including potential generic and oral competition for Copaxone(R)), the impact of continuing consolidation of our distributors and customers, our ability to identify, consummate and successfully integrate acquisitions (including the acquisition of Cephalon), interruptions in our supply chain or problems with our information technology systems that adversely affect our complex manufacturing processes, intense competition in our specialty pharmaceutical businesses, any failures to comply with the complex Medicare and Medicaid reporting and payment obligations, our exposure to currency fluctuations and restrictions as well as credit risks, the effects of reforms in healthcare regulation, adverse effects of political or economical instability, major hostilities or acts of terrorism on our significant worldwide operations, increased government scrutiny in both the U.S. and Europe of our agreements with brand companies, dependence on the effectiveness of our patents and other protections for innovative products, our ability to achieve expected results through our innovative R&D efforts, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, uncertainties surrounding the legislative and regulatory pathway for the registration and approval of biotechnology-based products, potentially significant impairments of intangible assets and goodwill, potential increases in tax liabilities resulting from challenges to our intercompany arrangements, our potential exposure to product liability claims to the extent not covered by insurance, the termination or expiration of governmental programs or tax benefits, current economic conditions, any failure to retain key personnel or to attract additional executive and managerial talent, environmental risks and other factors that are discussed in our Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission.

References:

1. Jeffrey H. Lipton, MD, PhD; Hagop M. Kantarjian, MD; Franck E. Nicolini, et al. Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) Resistant/Intolerant to Two or Three Approved Tyrosine-Kinase Inhibitors (TKIs). Abstract presented at: Annual Meeting of the American Society of Clinical Oncology. 2012 June 1-5; Chicago, IL
2. Luke Akard, MD; Hagop M. Kantarjian, MD; Franck E. Nicolini, et al. Omacetaxine Mepesuccinate in Chronic-Phase Chronic Myeloid Leukemia (CML) In Patients Resistant, Intolerant, or Both to Two or More Tyrosine-Kinase Inhibitors (TKIs). Abstract presented at: Annual Meeting of the American Society of Clinical Oncology. 2012 June 1-5; Chicago, IL.
3. Meir Wetzler, MD; Hagop M. Kantarjian, MD; Franck E. Nicolini, et al. Pooled Safety Analysis of Omacetaxine Mepesuccinate in Patients With Chronic Myeloid Leukemia (CML) Resistant to Tyrosine-Kinase Inhibitors (TKIs). Abstract presented at: Annual Meeting of the American Society of Clinical Oncology. 2012 June 1-5; Chicago, IL.
4. Data on File.
5. Blood. November 12, 2009 vol. 114 no. 20 4361-4368. “The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up.” Ravin J. Garg, Hagop Kantarjian, et al. http://bloodjournal.hematologylibrary.org/content/114/20/4361.full. Accessed May 15, 2012.
6. Leukemia. (2006) 20, 664670. “Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL.” D M Ross, S Branford, et al. http://www.nature.com/leu/journal/v20/n4/full/2404139a.html. Accessed May 17, 2012.
7. National Cancer Institute. General Information About Chronic Myelogenous Leukemia. http://www.cancer.gov/cancertopics/pdq/treatment/CML/Patient. Accessed March 22, 2012. Pages 1-2.
8. American Cancer Society. Cancer Facts and Figures 2012. Page 4.

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