Ariad Pharmaceuticals, Inc. suspended enrollment of patients into a clinical trial for its leukemia drug, Iclusig, as directed by the U.S. Food and Drug Administration (FDA) after some patients experienced blood clots and heart damage. Iclusig continues to be available to patients with resistant or intolerant chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia at the approved dose, the company announced.
“We believe that the actions we are taking will help us ensure the most appropriate and safe use of Iclusig,” Harvey J. Berger, M.D., chairman and chief executive officer of Ariad, said in a press release that also stated the FDA is planning to issue a Drug Safety Communication on the drug. The FDA originally approved Iclusig in Dec. 2012 under the agency’s accelerated approval program, which provides patients earlier access to promising new drugs while the company conducts additional studies; at that date, the FDA noted the possibility of side effects, including blood clots and liver problems.
Results of Ongoing Trials
After 24 months of clinical trials, Ariad reported that 11.8 percent of patients taking Iclusig experienced a serious arterial thrombosis: 6.2 percent experienced cardiovascular events, four percent experienced cerebrovascular events, and 3.6 percent experienced peripheral vascular events. Combined, non-serious and serious arterial and venous adverse events occurred in nearly 20 percent of Iclusig-treated patients, with some experiencing more than one type of negative effect.
“With two years of follow up, we have learned a great deal about both the efficacy and safety of Iclusig in patients with Philadelphia-positive leukemias,” Berger stated in the press release.
The company anticipates resuming trial enrollment after making modifications, including changes in dosage. Patients who are currently receiving Iclusig, a kinase inhibitor, in clinical trials will continue with a reduction in dose implemented on a trial-by-trial basis. Collected data from the trials demonstrate continued efficacy after dose reduction.
Iclusig targets an abnormal tyrosine kinase — a type of enzyme that activates proteins — expressed in both chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase or blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia and has a more aggressive course than CML.
Going forward, Ariad will exclude patients who have experienced prior arterial thrombosis resulting in heart attack or stroke from future clinical trials for the drug. Patients currently enrolled in a separate trial for the drug will take a reduced dosage. Reuters reported that Iclusig is also being tested in seven mid-stage studies for lung cancer, thyroid cancer, and another form of blood cancer; the company’s shares fell 57 percent to $7.44 in trading before the U.S. stock market opened on Wednesday.
A global oncology company headquartered in Massachusetts and Switzerland, Ariad primarily designs small-molecule drugs that overcome resistance to existing cancer medicines. In particular, the company is working in the areas of chronic and acute leukemia, lung cancer, and other difficult-to-treat cancers.