Drug Name (Brand / Generic)
Iclusig / ponatinib
Company / Licensee
Bcr-Abl tyrosine-kinase inhibitor (TKI)
Chronic Myeloid Leukaemia (CML) and Philadelphia-Chromosome Positive Acute Lymphoblastic Leukaemia (Ph+ALL)
Approved in the US
Iclusig (ponatinib) is indicated for the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL). The drug is discovered, developed and marketed by Ariad Pharmaceuticals.
Ariad received approval for Iclusig from the US Food and Drug Administration (FDA), in December 2012, for the treatment of the two rare diseases: CML and Ph+ALL.
Ariad obtained a positive opinion from the CHMP of the European Medicines Agency (EMA) for the approval of Iclusig in Europe, in January 2013. The EMA is expected to take a final decision on the approval of Iclusig in mid-2013.
Chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia
Chronic myeloid leukaemia is a type of cancer that is characterised by the unregulated growth of white blood cells in the bone marrow. Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) is a subtype of leukaemia that is more aggressive than CML.
It is estimated that CML is diagnosed in about 7,000 new patients every year in Europe.
Iclusig’s mechanism of action against CML and Ph+ALL
Iclusig contains multi-targeted tyrosine-kinase inhibitors. The drug targets oncogenic BCR-ABL gene, which produces BCR-ABL protein. The drug also reduces the size of tumours expressing native or T315I mutant BCR-ABL.
The drug is available in the form of tablets for oral administration.
Clinical trials on Iclusig (ponatinib) and outcomes
Ariad initiated a Phase II clinical study on Iclusig in September 2010. The study, named as PACE, enrolled over 440 patients across 68 study centres located in the US and Europe. It is expected to be completed by October 2020.
The primary outcome measure of the study is to find major cytogenetic response (MCyR). The secondary outcome measures include finding the clinical response, molecular response, clinical outcomes and safety.
Ariad initiated Phase III clinical trials on Iclusig in July 2012. The study is name Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC). The open label, randomised, parallel assignment will enrol 528 patients across 76 study locations in the US and Europe. It is expected to be completed by 2021.
The primary outcome measure of the study is to find the major molecular response (MMR) rate in 12 months time. The secondary outcome measures include finding the MMR rate, complete cytogenetic response (CCyR) rate, progression-free survival and overall survival.
Iclusig obtained approval from the FDA based on the results of a Phase III open-label, multicentre, international clinical study which enrolled over 449 patients with CML and Ph+ALL. The patients who became eligible for efficacy analysis were 444. The patients were administered with one of the cohorts, based on disease phase. The patients were administered with 45mg of Iclusig once-daily.
The study’s results showed that the primary endpoint of cytogenetic response (MCyR) was achieved in about 54% of the patients who were treated with Iclusig.
Marketing Iclusig in the US and worldwide
Bosulif (bosutinib) is an investigational drug indicated for treating Philadelphia chromosome positive Chronic Myelogenous Leukaemia (Ph+ CML).
Ariad holds the marketing rights for Iclusig in the US. Ariad commercially launched the drug in the US market in March 2013. The company expects to launch Iclusig across Europe by July 2013. It also expects to get regulatory approval for Iclusig in Canada, Switzerland and Australia by the second quarter of 2013.
The other medications available in the market for the similar indications include Bosulif developed by Pfizer, Synribo developed by Teva Pharmaceutical Industries, Srycel manufactured by Bristol-Myers Squibb, and Glivec developed by Novartis.