Ponatinib Meets Primary Endpoint of Superior Function for Newly-Diagnosed Ph+ Acute Lymphoblastic Leukemia


Ponatinib could be the first targeted treatment approved in the United States for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Ponatinib with reduced-intensity chemotherapy led to higher rates of minimal residual disease (MRD)-negative complete remission (CR) than imatinib in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in the PhALLCON phase 3 trial. The primary endpoint of the 3 trial was to determine superiority of ponatinib against imatinib as an effective treatment option.

“Ph+ ALL is a fast-progressing disease with no targeted treatments currently approved in the frontline for patients in the US,” said Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, in a press release.

PhALLCON is a phase 3, randomized, international, open-label, multicenter trial that evaluated the safety and efficacy of ponatinib versus imatinib as a combination therapy with reduced-intensity chemotherapy as frontline therapy in newly diagnosed patients with Ph+ ALL.

PhALLCON is the only head-to-head clinical trial comparing tyrosine kinase inhibitors (TKIs) as a frontline treatment for Ph+ ALL.

Ponatinib was found to improve long-term patient outcomes by reducing residual disease. It is a third-generation and pan-mutational TKI that targets BCR-ABL1, which is expressed in both Ph+ ALL and chronic myeloid leukemia (CML).

Ponatinib works by inhibiting native and treatment-resistant mutations, BCR-ABL1 and its activity. It also inhibits treatment-resistant mutations, particularly the T315I mutation, which is the most treatment-resistant variant of BCR-ABL1.

The safety did not observably change since it was last evaluated. The most common adverse events (AEs), which occurred in more than 20% of patients, include rash and related conditions, arthralgia, abdominal pain, headache, constipation, and arterial occlusive events, along with other AEs. Venous thromboembolic events have also been observed, along with heart failure, liver failure, and fatalities.

Ponatinib received full FDA approval in 2016. Ponatinib is indicated to treat adult patients with chronic-phase CML who were resistant or intolerant to 2 or more kinase inhibitors. Ponatinib is also indicated to treat accelerate-phase or blast-phase CML or Ph+ ALL, along with T315I+ CML or T315I-positive Ph+ ALL.

Ph+ ALL affects approximately 25% of patients with ALL in the United States. It is a rare type of ALL characterized by a Philadelphia chromosome and caused by an abnormally long chromosome. The disease is associated with poor long-term outcomes, Farajallah explained. “There is an urgent need for an effective treatment that can suppress the development of difficult-to-treat mutations,” Farajallah said.

Data from the PhALLCON study will be discussed with regulators in the near future. Experts then hope to share it with the scientific community.

“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,” said Farajallah in the press release.


Takeda. Phase 3 Trial of ICLUSIG® (ponatinib) Met Primary Endpoint in Newly-Diagnosed Ph+ ALL, a Setting with No Targeted Treatments Approved in the US. News Release. November 17, 2022. Accessed on November 17, 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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