Ponatinib Produces Higher Rates of Minimal Residual Disease-Negative Complete Remission in Ph+ ALL


Ponatinib (Iclusig; Takeda) combined with reduced-intensity chemotherapy achieved higher minimal residual disease-negative complete remission rates in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia compared to imatinib.

Ponatinib (Iclusig; Takeda) combined with reduced-intensity chemotherapy achieved the primary endpoint of the phase 3 PhALLCON trial, with higher minimal residual disease (MRD)-negative complete remission (CR) rates in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) compared to imatinib. Prior research has linked MRD-negativity with improved long-term outcomes for patients.

Ponatinib is the only pan-mutational, third-generation tyrosine kinase inhibitor (TKI) that targets BCR::ABL1, an abnormal tyrosine kinase expressed in chronic myeloid leukemia (CML) and Ph+ ALL. It also treats all known single, treatment-resistant mutations, such as T315I, which is the most resistant T315I mutation.

“Ph+ ALL is a fast-progressing disease with no targeted treatments currently approved in the frontline for patients in the US. There is an urgent need for an effective treatment that can suppress the development of difficult-to-treat mutations, which are associated with poor long-term outcomes,” said Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, in a press release. “We are excited to see how Iclusig may be able to address this gap in care for these patients and look forward to sharing the results.”

Ph+ ALL is a rare form of the disease affecting approximately 25% of adult patients with ALL in the United States. The disease is characterized by the presence of the abnormal Philadelphia chromosome gene.

Patients who are Ph+ have an abnormal chromosome that forms when pieces of chromosomes 9 and 22 switch places. This activity causes a longer chromosome 9 and a shorter chromosome 22, which leads to the development of BCR::ABL1 and is associated with Ph+ ALL.

Ponatinib is a targeted therapy developed via a computational and structure-based drug-design platform that was specifically developed to limit the activity of BCR::ABL1 and its mutations. The drug inhibits native BCR::ABL1 and all BCR::ABL1 treatment-resistant mutations.

Ponatinib was approved by the FDA in November 2016 for the treatment of adult patients with chronic-phase (CP) CML who have resistance or intolerance to at least 2 prior TKIs, accelerated-phase (AP) or blast-phase (BP) CML or Ph+ ALL for whom no other TKI is indicated, and T315I+ CML (CP, AP or BP) or T315I-positive Ph+ ALL.

Ponatinib is not indicated and not recommended for the treatment of newly diagnosed CP-CML.

PhALLCON is a randomized, international, open-label multicenter trial analyzing the efficacy and safety of ponatinib compared with imatinib in combination with reduced-intensity chemotherapy as a frontline treatment for adults with Ph+ ALL. The trial did not identify any new safety signals.

Takeda said these data will be discussed with regulatory agencies and presented to the scientific community in the future.


Phase 3 Trial of ICLUSIG® (ponatinib) Met Primary Endpoint in Newly-Diagnosed Ph+ ALL, a Setting with No Targeted Treatments Approved in the US. Takeda. News release. November 16, 2022. https://www.takedaoncology.com/news/news-releases/phase-3-trial-of-iclusig-ponatinib-met-primary-efficacy-endpoint-in-frontline-ph-all-where-no-other-targeted-treatments-are-currently-approved-in-the-us/

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