Wedoany.com Report on Feb 10th, The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the indication of Iclusig (ponatinib) to be used in combination with low-intensity chemotherapy for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). If this recommendation is approved by the European Commission, it will enable the use of this drug at an earlier stage of the disease, rather than being limited to those with resistance or intolerance.
Ponatinib, the active ingredient in the inhibitor Iclusig, is a tyrosine kinase inhibitor that works by inhibiting BCR-ABL tyrosine kinase. BCR-ABL is a constitutively active oncoprotein expressed in Ph+ leukemia cells, driving abnormal cell proliferation. By blocking its kinase activity, ponatinib can inhibit the growth of leukemia cells and delay disease progression.
Previously, the inhibitor Iclusig was authorized for the treatment of patients with chronic myeloid leukemia in chronic phase, accelerated phase, or blast phase who are resistant or intolerant to dasatinib or nilotinib, or for whom subsequent imatinib therapy is unsuitable, as well as for patients carrying the T315I mutation. Additionally, the drug is indicated for Ph+ ALL patients who are resistant or intolerant to dasatinib when imatinib is unsuitable.
In the Phase 3 PhALLCON trial, 245 newly diagnosed Ph+ ALL patients were randomly assigned to either the ponatinib group (164 patients) or the imatinib group (81 patients). Results showed that the minimal residual disease (MRD)-negative complete remission rate was significantly higher in the ponatinib group compared to the imatinib group (34% vs 17%), and the MRD-negative rate was also higher (43% vs 21%). The median duration of MRD negativity and time to treatment failure were not reached in the ponatinib group, while they were 20.9 months and 21.9 months, respectively, in the imatinib group. Among the 232 patients with centrally confirmed p190 or p210 BCR-ABL subtypes, the MRD-negative complete remission rate was also higher in the ponatinib group (34.4% vs 16.7%), and the median event-free survival was not reached, compared to 29 months in the imatinib group.
Ponatinib carries a high risk of arterial and venous vascular events, requiring clinicians to assess patients' cardiovascular status before treatment and monitor them closely. Other adverse reactions may include infections, pancreatitis, fever, gastrointestinal pain, cardiovascular and cerebrovascular events, peripheral arterial occlusion, hypertension, hematological toxicity, acute kidney injury, cellulitis, and elevated lipase levels.
The CHMP recommends assessing cardiovascular status before initiating treatment and considering alternative therapies in specific clinical situations. Detailed recommendations for the new indication will be included in the updated summary of product characteristics and published on the EMA website in all official EU languages after the European Commission makes its final decision.
