Day two @ASH: Phase 2 clinical trial results for new CML drug, FDA okays it today

Updated: 4:30 p.m. Friday, Dec. 14

The U.S. Food and Drug Administration approved ponatinib (Iclusig) for chronic myeloid leukemia and Philadelphia chromsome-positive acute lymphoblastic leukemia today.

Approval under the agency's accelerated review process occurred three months ahead of the deadline for FDA response.

Data from the phase 2 pivotal clinical trial provided the basis for approval.

"The availability of ponatinib will drastically improve the outcome of most patients with CML and Philadelphia-positive ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy. It is a safe and effective therapy that meets an unmet medical need and has to date overcome all known resistant mutations in preclinical studies" said Jorge Cortes, M.D., professor and deputy chair, in The University of Texas MD Anderson Cancer Center Department of Leukemia Friday.

Cortes led all clinical trials of Iclusig, the drug's new commercial name, developed by Ariad Pharmaceuticals of Cambridge, Mass.

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Sunday began with a news briefing about a promising phase II trial for ponatinib, a chronic myeloid leukemia investigational drug that helps patients who are resistant to existing CML drugs.

Jorge Cortes, M.D., professor in the Department of Leukemia, presented the phase II data at the 54th American Society of Hematology Annual Meeting and Exposition less than two weeks after the phase I results were published in the New England Journal of Medicine.

The new, larger trial also shows ponatinib sparks responses in patients with the T315I mutation and other drug-resistant mutations.

T315I is present in up to 20 percent of patients and blocks the docking station where three other successful CML drugs (Gleevec, Sprycel and Tasigna) normally connect to the mutant protein. Patients in the trial have had at least two of these drugs fail.

At 15.3 months of median follow up for patients in the initial, chronic phase of CML, 149 or 267 (54%) had a major cytogenetic response (reduction of CML cells in the blood) and 46% had a complete cytogenetic response (no CML cells in the bone marrow).

Of 64 chronic phase CML patients with the T315I mutation, 45 (70%) achieved major cytogenetic response with 66% reaching complete cytogenetic response.

Patients in the accelerated phase of CML and those in blast phase, the most serious condition, achieved major hematological responses (large reduction of leukemia cells in the blood) at rates of 51% and 34% respectively.

Of Ph+ALL patients, 41% percent achieved a major hematologic response. Major hematological response was the primary endpoint in the trial for patients with advanced disease.

"Ponatinib continues to show strong activity in heavily pretreated patients with resistant mutations, who have limited options at present," Cortes says. He notes that clinical studies of ponatinib in earlier stages of CML and Philadelphia Chromosome positive acute lymphoblastic leukemia are under way.

The drug's maker, ARIAD Pharmaceuticals, has filed for regulatory approval in the United States and the European Union based on results from the pivotal phase II trial, known as PACE.