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FDA Approves Synribo for CML

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The FDA has approved omacetaxine mepesuccinate for the treatment of adult patients with Philadelphia chromosome-positive CML who have progressed after treatment with at least two prior TKIs.

Jorge E. Cortes, MD

The FDA has approved omacetaxine mepesuccinate (Synribo) for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) who have progressed after treatment with at least two prior tyrosine kinase inhibitors (TKIs).

The approval was based on response rate, as a surrogate endpoint under the FDA Accelerated Approval Program. Prior to the approval, further options were limited for patients who failed treatment with a TKI, representing an unmet medical need.

“While the CML treatment landscape has seen advancements with available TKI treatments, there are still cases where patients may not be able to continue using TKIs due to issues such as resistance, intolerance, suboptimal response, and disease progression,” said Jorge E. Cortes, MD, deputy chair and professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “With Synribo, physicians will now have access to another option, offering potential hope to patients who experience treatment failure.”

The data for the approval came from the combination of two phase II trials that examined subcutaneous omacetaxine mepesuccinate in patients with chronic phase (CP) or accelerated phase (AP) CML. The FDA applied additional eligibility criteria that removed some patients from its efficacy analysis.

In the total, the FDA analysis assessed 76 patients with CP-CML and 35 with AP-CML. A major cytogenetic response (MCyR) was observed for a median duration of 12.5 months in 14 of the patients with CP-CML, after 3.5 months of treatment. Additionally, 5 patients with AP-CML experienced a major hematologic response (MaHR) that lasted 4.7 months and occurred after 2.3 months of receiving treatment.

An analysis of the 2 combined trials that was presented at the 2012 ASCO annual meeting examined the efficacy of subcutaneous omacetaxine mepesuccinate in 122 patients. Of these patients, 62 had received 2 prior TKIs (100% imatinib; 76% dasatinib; 24% nilotinib) and 60 had received 3 TKIs.

For patients receiving 2 prior TKIs, the analysis reported that 12 patients out of 45 (27%) with CP-CML experienced MCyR for a median duration of 17.7 months and 6 of 17 (35%) with AP-CML had MaHR for a median duration of 13.4 months.

Those who previously had received 3 TKIs also experienced significant results when given subcutaneous omacetaxine mepesuccinate. Four out of 36 (11%) patients with CP-CML had MCyR and 5 of 24 (21%) with AP-CML had MaHR for a median duration of 6.4 months.

Richard Pazdur, MD

The most common side effect reported during the study was thrombocytopenia, which occurred in 71% of those in the 2 TKI group and in 48% for those receiving 3. Other commonly reported adverse events were anemia, neutropenia, febrile neutropenia, diarrhea, nausea, weakness and fatigue, injection site reaction, and lymphopenia.

“Today’s approval provides a new treatment option for patients who are resistant to or cannot tolerate other FDA-approved drugs for chronic or accelerated phases of CML,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “Synribo is the second drug approved to treat CML in the past two months.”

On September 4, 2012, the FDA approved the dual TKI bosutinib (Bosulif) for the treatment of Ph+ CML, following resistance or intolerance to previous therapies.

According to the National Institutes of Health, approximately 5430 new cases of CML will occur in 2012.

Synribo is manufactured by Teva Pharmaceutical Industries Ltd.

Nicolini FE, Lipton JH, Kantarjian H, 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). J Clin Oncol. 2012;30(suppl; abstr 6513).

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