Synribo (Omacetaxine Mepesuccinate) For Myelogenous Leukemia, Approved By FDA

Synribo (omacetaxine mepesuccinate) has been approved by the FDA (US Food and Drug Administration) for the treatment of chronic myelogenous leukemia (CML) in adult patients.

Chronic myelogenous leukemia is also known as chronic myeloid leukemia.

Approximately 5,430 are expected to be diagnosed with CML, a blood and bone marrow disease, in 2012, says the NIH (National Institutes of Health). Synribo is indicated for patients who have already received two types of drugs called tyrosine kinase inhibitors (TKIs), but their cancer continued to progress.

Resistance to drug treatment is common in CML. Researchers at the Keck School of Medicine of the University of Southern California, explained in the journal Cell that they found high concentrations of a specific mutator protein in cells that develop resistance to CML treatment. The protein, called activation-induced cytidine deaminase (AID), which usually mutates antibody genes in B cells, encourages resistance to the standard treatment for CML patients (Gleevec).

Synribo, an alkaloid from Cephalotaxus harringtonia, inhibits proteins that encourage the development of cancerous cells. It is administered subcutaneously (under the skin) twice daily for 14 consecutive days over a 28-day cycle until there is a hematologic response (white blood cell counts normalize). It is then injected twice a day for seven consecutive days over a 28-day cycle perpetually, as long as the patient continues to benefit from the medication.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products, the Center for Drug Evaluation and Research, FDA, said:

“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. Synribo is the second drug approved to treat CML in the past two months.”

Bosulif (bosutinib) was approved by the FDA on September 4th, 2012, for the treatment of chronic, accelerated or blast phase Philadelphia chromosome positive CML, in patients who are unable to tolerate other medications or therapies.

Synribo’s approval went through the FDA’s accelerated approval program. In accelerated approval programs the FDA can pass a drug that is indicated for the treatment of a serious disease, based on clinical data that shows that the medication has an effect on a secondary or surrogate endpoint, which most likely is of benefit to patients.

Under the accelerated approval program, patients can have earlier access to medications while the pharmaceutical or biologics company carries out additional clinical trials to confirm efficacy and safety.

As Synribo is indicated for the treatment of a rare disease, it also received FDA orphan designation.

The FDA evaluated Synribo by assessing the results of studies which used a combined cohort of patients whose CML had progressed after they were treated with at least two TKIs. All the participants received Synribo.

During chronic phase CML, Synribo reduced the percentage of cells expressing the Philadelphia chromosome genetic mutation which exists in the majority of CML cases. Out of 76 patients, 14 (18.4%) achieved a reduction within 3.5 months (average). The median length of the reduction was 12.5 months.

In an online communiqué, the FDA wrote on Friday:

“In accelerated phase CML, Synribo’s effectiveness was determined by the number of patients who experienced a normalization of white blood cell counts or had no evidence of leukemia (major hematologic response, or MaHR). Results showed five out of 35 patients (14.3 percent) achieved MaHR in an average time of 2.3 months. The median duration of MaHR in these patients was 4.7 months.”

The following were the most commonly reported side effects during the clinical trials:

• Thrombocytopenia – low levels of platelets in the blood
• Anemia – low red blood cell count
• Neutropenia – a drop in the number of white blood cells that fight infection, which can lead to fever (febrile neutropenia) and infection), diarrhea, nausea, weakness and fatigue
• Infection site reaction
• Lymphopenia – a drop in the lymphocyte count in the blood

Jorge E. Cortes, M.D., deputy chair and professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said:

“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. With SYNRIBO, physicians will now have access to another option, offering potential hope to patients who experience treatment failure.”