The Pharmacovigilance Risk Assessment Committee ( PRAC ) of the European Medicines Agency ( EMA ) has concluded its review of Iclusig ( Ponatinib ) under the Article 20 referral procedure and has recommended that Iclusig continue to be used in Europe in accordance with its already approved indications.
The authorized indications of Iclusig in Europe, as approved in July 2013, are as follows:
the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukaemia ( CML ) who are resistant to Dasatinib ( Sprycel ) or Nilotinib ( Tasigna ); who are intolerant to Dasatinib or Nilotinib and for whom subsequent treatment with Imatinib ( Glivec, Gleevec ) is not clinically appropriate; or who have the T315I mutation;
the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia ( Ph+ ALL ) who are resistant to Dasatinib; who are intolerant to Dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
Other recommendations made by the PRAC related to the Iclusig Summary of Medicinal Product Characteristics ( SmPC ) include, (1) patient monitoring for response according to standard clinical guidelines, (2) consideration of Iclusig dose-reduction following achievement of major cytogenetic response with subsequent monitoring of response and, (3) consideration of Iclusig discontinuation if a complete haematologic response has not been achieved by three months.
Further information is provided indicating that the risk of vascular occlusive events is likely dose-related.
The PRAC is the Committee at the EMA that is responsible for assessing and monitoring safety issues for human medicines. The PRAC's recommendations are considered by the CHMP when it adopts opinions for centrally authorized medicines and referral procedures.
Chronic myeloid leukaemia is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe. CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis.
Ph+ ALL is a subtype of acute lymphoblastic leukaemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than chronic myeloid leukaemia and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.
Ponatinib is a kinase inhibitor. The primary target for Ponatinib is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia ( CML ) and Philadelphia-chromosome positive acute lymphoblastic leukemia ( Ph+ ALL ). Ponatinib 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. ( Xagena )
Source: Ariad, 2014