- Full approval granted through completion of accelerated approval commitments for rare cancer patients who may have no other targeted treatment options
- New label update for CP-CML reflects 55 percent major cytogenetic response rate (MCyR), and 39 percent major molecular response rate (MMR), a key secondary endpoint deeper than cytogenetic response
- Safety and efficacy profile updated based on 48-month follow-up
CAMBRIDGE, MA, USA I November 29, 2016 I ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that the U.S. Food and Drug Administration (FDA) has granted Iclusig® (ponatinib) full approval for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated; and for the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I positive Ph+ ALL. Iclusig was initially approved in December 2012 under the FDA’s accelerated approval program, which provides patients earlier access to promising new drugs that treat serious conditions based on a surrogate endpoint while the company conducts additional studies to confirm the drug’s clinical benefit. The therapy was granted the FDA’s orphan drug designation because it is intended to treat a rare disease or condition.
This full approval and label update is based on 48-month follow-up data (as of August 2015) from the pivotal Phase 2 PACE clinical trial of Iclusig in heavily pretreated patients with resistant or intolerant CML or Ph+ ALL. These data were presented at the 2016 meetings of the American Society for Clinical Oncology and the European Hematology Association (EHA).
“The data on Iclusig continue to show that with a minimum follow-up of 48 months, many chronic phase CML patients in the PACE trial have retained long-term cytogenetic and molecular responses,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “We are pleased to have received full approval of this medicine that was discovered and developed by ARIAD scientists to address rare cancers for patients who may have no other targeted treatment option. With this label update we are also now able to communicate to physicians that patients have experienced deep responses on Iclusig, measured by major molecular response (MMR). We are continuing our efforts to understand the optimal Iclusig dose for patients with the OPTIC (Optimizing Ponatinib Treatment In CML) post-marketing study.”
“The longer follow up of the PACE study confirms the clinical benefit of ponatinib in this setting. We had learned from the initial report of the high response rate with ponatinib among CML patients with resistance or intolerance to prior therapies. The four-year follow-up and updated safety profile demonstrate durability of responses in this heavily pre-treated population. These results solidify ponatinib as an important and valuable treatment option for refractory patients with CML where no other TKI therapy is appropriate, including those who have the T315I mutation,” stated Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and a leading investigator in the PACE trial.
“Prior to the approval of Iclusig, there were patients with CML for whom no targeted treatment was available, either because they had developed resistance mutations or intolerance to other approved treatments. For these patients, we now have a better understanding of the long-term treatment profile of Iclusig,” stated Greg Stephens, executive director of the National CML Society. “We have been impressed by the major molecular responses some patients have been able to achieve on Iclusig and by ARIAD’s commitment to supporting patient and caregiver needs.”
Four-Year PACE Trial Data Included in Labeling Update
The efficacy and safety of ponatinib in CML and Ph+ ALL patients resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation, were evaluated in the PACE trial. A total of 449 patients were treated with ponatinib at a starting dose of 45 mg/day. An estimated 93 percent of patients previously received two or more approved tyrosine kinase inhibitors (TKIs), and 56 percent of all patients had received three or more approved TKIs. Enrollment in the PACE trial was completed in October 2011.
Updated data on CP-CML patients (n=270) from the ongoing trial indicate that with a minimum follow-up of 48 months (data as of August 3, 2015), 110 patients continued to receive ponatinib. Additional data for CP-CML patients include:
- 55 percent of CP-CML patients achieved major cytogenetic response (MCyR) (primary endpoint) at any time.
- The median duration of MCyR (range 2.7 to 50+ months) has not been reached.
- 39 percent of patients achieved a major molecular response (MMR) at any time.
- The median duration of MMR (range 1.7 to 50+ months) has not been reached.
- With four years of follow-up, 33 percent (150/449) of all patients experienced arterial occlusive events (AOE). Twenty-one percent of patients experienced cardiac vascular, 12 percent experienced peripheral vascular and 9 percent experienced cerebrovascular arterial occlusive events, with some patients experiencing more than one type of AOE. Twenty-two percent experienced arterial occlusive serious adverse reactions (12% cardiac vascular, 8% peripheral vascular and 7% cerebrovascular).
- Six percent of all patients experienced a venous thromboembolic event.
- The most common any-grade treatment-emergent adverse events occurring in ≥ 20 percent of CP-CML patients included hypertension (69%), rash (63%), abdominal pain (48%), fatigue (47%), headache (43%), arterial ischemia (42%), dry skin (42%), constipation (41%), arthralgia (32%), nausea (28%), pyrexia (26%), peripheral neuropathy (24%), myalgia (24%), pain in extremity (23%), back pain (21%), diarrhea (20%). Post-marketing cases of reversible posterior leukoencephalopathy syndrome have been reported.
OPTIC Post-Marketing Trial
ARIAD is currently enrolling patients in the OPTIC post-marketing trial of Iclusig (ponatinib) which is expected to inform the optimal dosing of Iclusig. This randomized, dose-ranging trial is enrolling patients with CP-CML who are resistant to at least two approved TKIs. Patients are randomized equally to receive once-daily administration of 45 mg (cohort A), 30 mg (cohort B) or 15 mg (cohort C) of ponatinib. Patients in cohorts A and B will have their daily dose reduced to 15 mg upon achievement of MCyR. The primary endpoint of the trial is MCyR by 12 months for each cohort. ARIAD expects initial data from the OPTIC trial to be submitted to the American Society of Hematology (ASH) meeting in 2017.
About Iclusig® (ponatinib) tablets
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug-design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs. Iclusig is approved in the U.S., EU, Australia, Switzerland, Israel, Canada and Japan.
In the U.S., Iclusig is a kinase inhibitor indicated for the:
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
- Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL.
Please see the full U.S. Prescribing Information for Iclusig, including the Boxed Warning.
Iclusig is a registered trademark of ARIAD Pharmaceuticals, Inc.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts is focused on discovering, developing and commercializing precision therapies for patients with rare cancers. ARIAD is working on new medicines to advance the treatment of rare forms of chronic and acute leukemia, lung cancer and other rare cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).
SOURCE: Ariad Pharmaceuticals
