The latest addition to the arsenal of CML medications is omacetaxine (SYNRIBO), which the FDA grant full approval to in February 2014. The drug received accelerated approval in October 2012 and full approval had been withheld until the final results of its phase II study were available.
Omacetaxine is the only CML treatment that isn’t a TKI (tyrosine kinase inhibitor). The drug, formally known as homoharringtonine, inhibits the synthesis of key proteins involved in the CML disease process. It’s administered by an injection under the skin (subcutaneous). The dosing is two injections a day for two weeks in the first month, then as a twice-daily injection for seven days per month (so 1 week on, then 3 weeks with no injections).
Synribo is intended as a back-up treatment if someone is no longer responding to at least two other medications, such as imatinib, dasatinib or nilotinib.
The FDA includes warnings about a risk of low blood cell counts (with a 3% fatality rate), a potential for bleeding complications (so Aspirin and other blood thinners should be avoided), and hyperglycemia (so extra caution is needed for people with diabetes). The drug can harm a developing fetus so it should not be used by pregnant women.
The FDA approval of omacetaxine was based on data from 111 people that showed that 18% achieved a major cytogenetic response lasting about five months (Alvandi and colleagues. Oncologist 2014;19:94-99). The safety evaluation showed that the most common adverse effects with the drug were a low blood cell counts, diarrhea, nausea, fatigue, fever and infection.
These data were recently presented at the American Society of Hematology annual meeting (ASH). According to that report, most people in the study had not responded to three prior medications (Cortes and colleagues. ASH 2013; abstract 2743). The median survival was 40 months for people with chronic-phase CML, and 14 months for those with accelerated-phase CML based on 24-month results. Most people had to interrupt treatment at some point due to problems with side effects.
A smaller phase II study reported similar results, with 22% achieving a major cytogenetic response (Cortes and colleagues. Am J Hematol 2013;88:350-354).
The FDA judged that omacetaxine provided real benefits to this very ill group of people who were no longer responding to one of the TKI medications.