Product Name: Ponatinib

Specification: 45 mg × 30 tablets

Manufacturer: Everest Pharmaceuticals

Ponatinib is a third-generation BCR-ABL tyrosine kinase inhibitor (TKI). On December 14, 2012, Ponatinib was granted accelerated approval by the U.S. FDA for marketing and sale. It is indicated for the treatment of chronic myeloid leukemia (CML) with the ABL T315I mutation, or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); it may also be used to treat CML or ALL in patients who have developed resistance to, or are intolerant of, previous tyrosine kinase inhibitors (TKIs).

Although first- and second-generation TKIs have improved clinical outcomes for patients with CML and Ph+ ALL, drug resistance still occurs in some patients with BCR-ABL mutations—particularly the T315I mutation. Prior to the approval of the third-generation TKI, Ponatinib, no TKIs were available on the market capable of overcoming the issues of resistance, refractoriness, or intolerance observed in these patients with BCR-ABL mutations. Among patients with accelerated-phase CML, blast-phase CML, and Ph+ ALL, Ponatinib achieved major hematologic response rates of 55%, 31%, and 41%, respectively. Consequently, Ponatinib stands as a potent oral TKI and represents a critically important clinical option for patients with refractory CML—especially those harboring the T315I mutation.

In a post-hoc, retrospective, and indirect comparison of overall survival (OS)—contrasting patients treated with Ponatinib monotherapy in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial against patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) as reported by the European Group for Blood and Marrow Transplantation (EBMT) Registry—the CML cohort was stratified by disease phase, and the Ph+ ALL cohort was analyzed separately. Kaplan-Meier survival curves and multivariate Cox proportional hazards models were employed to compare OS between the intervention groups, with adjustments made for time from diagnosis to intervention, age, gender, and geographic region; OS rates at 24 and 48 months, as well as median OS, were reported. When administering Ponatinib, close attention must be paid to congestive heart failure, hypertension, pancreatitis, hemorrhage, cardiac arrhythmias, and various patient physiological parameters. Congestive Heart Failure: Monitor patients for signs and symptoms of congestive heart failure and treat as clinically indicated. Hypertension: Monitor for hypertension and treat as clinically indicated. Pancreatitis: Monitor serum lipase levels monthly; interrupt or discontinue Ponatinib treatment. Hemorrhage: Interrupt Ponatinib treatment in cases of severe hemorrhage. Fluid Retention: Monitor patients for signs of fluid retention; interrupt or discontinue Ponatinib treatment.

【Indications】

Chronic Myeloid Leukemia (CML)

Indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase CML who are resistant to or intolerant of prior tyrosine kinase inhibitor (TKI) therapy.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Indicated for adult patients who are resistant to or intolerant of prior TKI therapy.

【Recommended Dosage】

45 mg orally once daily, with or without food, until disease progression or the occurrence of intolerable adverse reactions.

If a complete hematologic response has not been achieved after 3 months (90 days) of treatment, consider discontinuing the drug.

【Warnings and Precautions】

Thrombosis:

Arterial Thrombosis: Use of Ponatinib in patients with cardiovascular risk factors increases the risk of arterial thrombosis. Consider interrupting Ponatinib treatment in patients who experience an arterial thrombotic event.

Venous Thromboembolism: Consider dose adjustment or discontinuation of treatment in patients who experience severe venous thromboembolism.

Hepatotoxicity: Monitor liver function parameters at least monthly or as clinically indicated.

Congestive Heart Failure: Monitor patients for signs or symptoms consistent with congestive heart failure and treat as clinically indicated, including the interruption of Ponatinib treatment.

Hypertension: Monitor and manage elevated blood pressure during Ponatinib treatment. Pancreatitis: Monitor serum lipase levels every 2 weeks during the first 2 months of treatment, and thereafter monthly or as clinically indicated. In cases of elevated lipase levels accompanied by abdominal symptoms, interrupt Ponatinib treatment and evaluate the patient for pancreatitis. Do not consider resuming treatment until symptoms have completely resolved and lipase levels have returned to less than 1.5 times the Upper Limit of Normal (ULN).

Hemorrhage: Intracranial hemorrhage and gastrointestinal hemorrhage are the most common serious hemorrhagic events. Most hemorrhagic events occur in patients with thrombocytopenia.

Arrhythmias: Advise patients to report signs and symptoms of a rapid heart rate (e.g., palpitations, dizziness).

Myelosuppression: Monitor complete blood counts (CBC) every 2 weeks during the first 3 months of treatment, and thereafter monthly or as clinically indicated; adjust the dosage as recommended.

Tumor Lysis Syndrome: Ensure adequate hydration and treat elevated uric acid levels prior to initiating Ponatinib treatment.

Impaired Wound Healing and Gastrointestinal Perforation: Interrupt Ponatinib treatment for at least 1 week prior to major surgery. The decision to resume treatment after surgery should be based on clinical judgment regarding wound healing.

Embryo-Fetal Toxicity: If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women are advised to avoid becoming pregnant while undergoing treatment.

[Adverse Reactions]

The most common non-hematologic adverse reactions (≥20%) are hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions include thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia. Product Specifications

Product Name: Ponatinib Ponaxen 45 mg EVEREST (Zhufeng) — Ponatinib 45 mg × 30 Tablets

Common Name: Ponatinib

Active Ingredient: Ponatinib

Dosage Form: Tablets

Specification: 45 mg × 30 Tablets

Manufacturer: Everest Pharmaceuticals

Indications:

Chronic Myeloid Leukemia (CML)

Used for the treatment of adult patients with chronic phase, accelerated phase, or blast phase Chronic Myeloid Leukemia (CML) who are resistant to or intolerant of prior tyrosine kinase inhibitor therapy.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Used for adult patients who are resistant to or intolerant of prior tyrosine kinase inhibitor therapy.

Dosage and Administration: 45 mg orally once daily, taken with or without food, until disease progression occurs or until intolerable adverse reactions develop.

If a complete hematologic response has not been achieved after 3 months (90 days) of treatment, discontinuation of the drug should be considered.