The US Food and Drug Administration (FDA) has approved revised US Prescribing Information (USPI) and a Risk Evaluation and Mitigation Strategy (REMS) for ponatinib, marketed as Iclusig, according to an announcement from Ariad Pharmaceuticals, Inc, the company developing the drug. The USPI and REMS allow for the immediate resumption of ponatinib’s marketing and commercial distribution. The USPI also includes a revised indication statement and a boxed warning, with alerts to the risk of vascular occlusive events and heart failure. The USPI also includes dosing recommendations, which remain at 45 mg daily.
The approval of the revised USPI for ponatinib was based on a review of clinical trial data, including a 24-month follow-up of the pivotal PACE (Ponatinib Ph ALL and CML Evaluation) trial, which
served as the basis for the drug’s approval in 2012.
Approximately 640 patients had obtained ponatinib through commercial channels in the United States at the end of October 2013. Ponatinib has since been made available on a case-by-case basis to 350 patients through emergency and single-patient investigational new drug (IND) applications.
“In less than 2 months of suspending marketing and commercial distribution of Iclusig in the US, we addressed the issues raised by the FDA and now are able to market and distribute Iclusig again in the US,” Harvey J. Berger, MD, chairman and chief executive officer of Ariad, said in a statement. “As we look ahead to relaunching Iclusig in the US and fulfilling our post-marketing requirements, we will continue to focus on understanding the benefits and risks of Iclusig treatment in patients with resistant or intolerant Philadelphia-positive leukemias.”
Ponatinib is approved for adult patients with:
• Chronic phase, accelerated phase, or blast phase T315I-positive chronic myeloid leukemia (CML)
• T315I-positive Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)
• Chronic phase, accelerated phase, or blast phase CML or Ph+ ALL for whom no other tyrosinekinase inhibitor therapy is indicated
The clinical development of ponatinib was placed on hold in early October 2013 while the FDA investigated the adverse events associated with the drug. This was shortly followed by the early termination of the phase III EPIC (Evaluation of Ponatinib versus Imatinib in CML) trial, which was examining ponatinib in the frontline setting for untreated patients with CML. The suspension
in distribution followed discussions between Ariad and the FDA.
Marty Duvall, executive vice president and chief commercial officer of Ariad, said that commercial and medical affairs teams will be deployed by mid-January. Duvall said distribution of
ponatinib will then begin and the company expects the drug will be “cash-flow positive from the onset.” Until then, the drug will be distributed with the IND mechanism.