Leukemia drug Iclusig (ponatinib) is the focus of a U.S. Food and Drug
Administration (FDA) Drug Safety Alert over its association with serious
blood clots. Ariad Pharmaceuticals, Inc. manufactures Iclusig.
The FDA has asked Ariad Pharmaceuticals to cease marketing of the dangerous
drug Iclusig after receiving reports of serious blood clots in patients'
veins and arteries. The drug received FDA clearance in December 2011 and
is used in the treatment of chronic myeloid leukemia (CML) and Philadelphia
chromosome positive acute lymphoblastic leukemia (Ph+ALL). Ariad describe
Iclusig as a kinase inhibitor that targets BCR-ABL, an abnormal tyrosine
kinase. In other words, Ariad interrupts the enzymes in cancer cells that
cause cancer to multiply. Iclusig is delivered in either 15 mg or 45 mg
In its current safety announcement, dated October 31, 2013, the agency
indicated that it would evaluate Iclusig and its risks-benefit profile,
and stated that patients treated with Iclusig should discuss treatment
with their heath care professionals. The new safety announcement is an
update to the agency's prior update dated October 11, 2013.
The FDA indicates that Iclusig patients who are not responding to treatment
should discuss alternate treatments with their physicians and their Iclusig
treatment should be stopped. In patients who are responding to Iclusig
and whose doctors feel the drug's risks are outweighed by its benefits,
patients should receive that treatment using a single-patient Investigational
New Drug (IND) application or the expanded access registry program. The
FDA indicated that it would work with Ariad on this plan. The agency also
stated that health care professions should not begin new patient treatment
for Iclusig unless all other treatment options have failed and, if new
Iclusig treatment is considered, and IND or expanded access registry program
should be used.
The agency's Iclusig probe revealed that about 24 percent of patients
enrolled in the Phase 2 clinical trial experienced significant adverse
vascular events; 48 percent of the patients in the Phase I clinical trial
also experienced similar side effects. Side effects were seen in as soon
as two weeks following treatment with Iclusig and included fatal and life-threatening
heart attack; stroke; blood flow loss to limbs that resulted in tissue
death and amputations; and severe blood vessel narrowing in the extremities,
heart, and brain, which required immediate surgery to restore the flow
of blood. Patients with no cardiovascular risk factors, including patients
in their 20s, experienced these adverse side effects when taking Iclusig.
Patients also suffered from significant adverse optical reactions, which
led to blindness or blurred vision and high blood pressure. Initial drug
trials also revealed that Iclusig could lead to blood clots (thrombosis)
and hepatoxicity (liver toxicity), which led to a black box warning on
Iclusig's label when it was approved. Other adverse reactions include
pancreatitis, hemorrhage, and water retention.
Iclusig was approved under an accelerated process; therefore Ariad was
mandated to conduct additional drug trials following approval. The FDA
warned that Iclusig could lead to an array of adverse reactions based
on these results and adverse report events.
Ariad announced that it ceased critical trial enrollment for Iclusig, that
dosing for Iclusig would be reduced from 45 mg, and that future clinical
trials will exclude patients diagnosed with a history of arterial thrombosis.
- The U.S. Food and Drug Administration: http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm
- Ariad Pharmaceuticals, Inc.: ARIAD Announces Temporary Suspension of Iclusig
Marketing in the United States