Asciminib (Scemblix – Novartis), an oral kinase inhibitor, has been approved by the FDA for treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) previously treated with ≥2 tyrosine kinase inhibitors and for adults with Ph+ CML in CP with a T315I mutation.

The FDA has approved omacetaxine mepesuccinate (Synribo – Teva), a cephalotaxine known for many years as homoharringtonine, for treatment of adults with chronic or accelerated phase chronic myeloid leukemia (CML) who are no longer responding to, or who could not tolerate, two or more tyrosine kinase inhibitors.

The October 2013 suspension of marketing and sales of ponatinib (Iclusig – Ariad) for treatment of leukemia1 has been lifted by the FDA, and the drug is expected to return to the market this month with narrower indications and heightened safety warnings.2 The reason for its suspension was a high incidence of thrombotic events, some of them fatal. The new indications limit use of the drug to patients with T315I-positive disease and those "for whom no other tyrosine kinase inhibitor is indicated," presumably because of resistance or intolerance.

1. In brief: ponatinib (Iclusig) marketing and sales suspended. Med Lett Drugs Ther 2013; 55:93.

2. FDA. FDA drug safety communication: FDA requires multiple new safety measures for leukemia drug Iclusig; company expected to resume marketing. Available at www.fda.gov. Accessed January 10, 2014.

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The FDA recently issued a Drug Safety Communication saying that it had asked the manufacturer of ponatinib (Iclusig – Ariad) to suspend marketing and sales of the drug because of the risk of life-threatening blood clots and severe narrowing of blood vessels.1 Ponatinib is a tyrosine kinase inhibitor that was granted accelerated approval by the FDA in December 2012 for treatment of chronic-, accelerated, or blast-phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) resistant to (or the patients were intolerant to) prior tyrosine kinase inhibitor therapy. It is the first tyrosine kinase inhibitor that is effective against the T315I mutation, which is present in up to 20% of patients with treatment-resistant CML.2

The labeling of Iclusig includes a warning about the risk of arterial thrombosis, but recent clinical trial results showed an unexpectedly high incidence of serious adverse vascular events, some fatal, which occurred in 24% of patients in one clinical trial with a median duration of 1.3 years and 48% in another with a median duration of 2.7 years. These adverse events occurred in some patients as early as 2 weeks after starting ponatinib. Neither trial included a control group. Blindness has occurred in some patients and in one of the trials, 8% of those treated with the drug developed heart failure.

Suspension of marketing and sales does not necessarily mean that Iclusig will be withdrawn permanently; it is the only option available for some treatment-resistant patients.3 The drug could be returned to the market, possibly with new labeling narrowing the selection of patients, lowering the dosage, or recommending use of aspirin concomitantly to decrease the risk of thrombosis.4

1. FDA Drug Safety Communication: FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales. Available at www.fda.gov. Accessed November 18, 2013.

2. Ponatinib (Iclusig) for CML and Ph+ ALL. Med Lett Drugs Ther 2013; 55:71.

3. JH Doroshow. Overcoming resistance to targeted anticancer drugs. N Engl J Med 2013; 369:1852.

4. Ariad expects narrower label, not withdrawal, for Iclusig following halted study. "The Pink Sheet" 2013; 75:16.

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Ponatinib (Iclusig – Ariad), a tyrosine kinase inhibitor, has been approved by the FDA for treatment of chronic-, accelerated-, or blast-phase chronic myeloid leukemia (CML) or Philadelphia chromosome- positive (Ph+) acute lymphoblastic leukemia (ALL) resistant to prior tyrosine kinase inhibitor therapy. It is the fifth tyrosine kinase inhibitor approved for the treatment of CML or Ph+ ALL.