Photo courtesy of the FDA
Health Canada has approved ponatinib hydrochloride (Iclusig) to treat adults with any phase of chronic myeloid leukemia (CML) or Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL patients with the T315I mutation and those who have exhibited prior TKI resistance or intolerance.
Ponatinib is approved under the Notice of Compliance with Conditions policy based on promising evidence of clinical effectiveness.
Products approved under this policy are intended for the treatment, prevention, or diagnosis of a serious, life-threatening, or severely debilitating illness. The products must have demonstrated promising benefit, be of high quality, and possess an acceptable safety profile based on a benefit/risk assessment.
These products either respond to a serious unmet medical need in Canada or have demonstrated a significant improvement in the benefit/risk profile over existing therapies.
Ponatinib will be made available in Canada through a controlled distribution program. Prescribers who have completed the certification procedure will be able to prescribe the drug. Trained pharmacies will verify the prescriber’s certified status prior to dispensing ponatinib to the patient.
Health Canada’s decision to approve ponatinib was based on 2-year data from the phase 2 PACE trial.
A trial set to begin in mid-2015 will serve as the confirmatory trial for the Health Canada approval. Investigators will evaluate 3 starting doses of ponatinib in patients with refractory, chronic-phase CML who are resistant to at least 2 approved TKIs.
PACE trial
Researchers conducted this trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior TKI therapy, or who had the T315I mutation.
Ponatinib demonstrated anti-leukemic activity in these patients, prompting a major cytogenetic response (MCyR) in 56% of chronic-phase CML patients and in 70% of patients with the T315I mutation. MCyR within the first 12 months of treatment was the primary endpoint for chronic-phase patients.
In patients with advanced disease, 57% of accelerated-phase CML patients and 31% of blast-phase CML patients achieved a major hematologic response (MaHR). MaHR within the first 6 months was the primary endpoint for patients with advanced disease. In patients with Ph+ ALL, 41% achieved MaHR.
Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).
Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). Serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.
Extended follow-up data from the PACE trial, collected in 2013, suggested ponatinib can increase the risk of thrombotic events. When these data came to light, officials in the European Union and the US, where ponatinib had already been approved, began to investigate the drug.
Ponatinib was pulled from the US market for a little over 2 months, and trials of the drug were placed on partial hold while the Food and Drug Administration evaluated the drug’s safety. Ponatinib went back on the market in January 2014, with new safety measures in place.
The drug was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of ponatinib. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.
