U.S. FDA Approves Takeda’s Third-Generation TKI ICLUSIG® (ponatinib) for Adults with CP-CML Resistant or Intolerant to ≥2 Prior TKIs
Dec 21, 2020 00:47
CST Updated
00:47
Takeda
Biopharmaceutical Manufacturer
FDA
U.S. Food and Drug Administration
December 20, 2020 News /BioValleyBIOON/ -- Takeda Pharmaceutical Company Limited (Takeda) recently announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Iclusig (ponatinib), indicated for the treatment of chronic-phase (CP) chronic myeloid leukemia in patients who are resistant or intolerant to at least two prior kinase inhibitors.Leukemia(CML) adult patients.
The updated Iclusig prescribing information includes an optimized, response-guided Iclusig dosing regimen for the treatment of chronic-phase chronic myeloid leukemia (CP-CML): an initial dose of 45 mg, reduced to 15 mg upon achieving ≤1% BCR-ABL1IS. This dosing regimen is designed to maximize the benefit-risk profile of treatment by providing efficacy while reducing the risk of adverse events (AEs), including arterial occlusive events (AOEs).
Takeda GlobalTumorPresident Teresa Bitetti stated: “FDA“The approval of the sNDA for Iclusig marks a significant milestone for the CML community. Although chronic-phase chronic myeloid leukemia (CP-CML) is generally manageable, many patients still face a poor long-term prognosis and have the potential to benefit from third-generation TKIs early in their treatment journey. Iclusig has demonstrated efficacy in many resistant patients, and its use at critical junctures can deliver meaningful outcomes for these individuals. We are excited about this updated label and believe it will help address gaps in the care of patients with CP-CML who are resistant to or intolerant of prior therapies by optimizing Iclusig treatment.”
This sNDA approval is based on data from the Phase 2 OPTIC trial (Iclusig for the treatment of CML) and the 5-year data from the Phase 2 PACE trial (Iclusig for the treatment of Ph+ ALL and CML).
The OPTIC trial enrolled patients with chronic-phase chronic myeloid leukemia (CP-CML) whose disease was highly resistant to previously administered tyrosine kinase inhibitors (TKIs); the majority (65%) had not achieved a response better than complete hematologic response (CHR) to their most recent TKI therapy. Data showed that at 12 months of treatment, 42% of the 88 patients receiving the newly approved response-guided optimized dosing regimen (dose reduced from 45 mg to 15 mg) achieved BCR-ABL1IS ≤1%, the primary endpoint of the OPTIC trial, and 73% of patients maintained this response during a median follow-up period of 28.5 months. In this trial, 13% of patients experienced arterial occlusive events (AOEs) of any grade, and 7% experienced AEs of grade ≥3.
The PACE trial was conducted in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who were resistant or intolerant to dasatinib or nilotinib, or who harbored the T315I mutation. A total of 449 patients received Iclusig at an initial dose of 45 mg once daily. It is estimated that 93% of patients had previously received ≥2 tyrosine kinase inhibitors (TKIs), and 56% had received ≥3 TKIs. Among the 267 patients with chronic-phase CML (CP-CML) enrolled in the trial, 55% achieved a major cytogenetic response after 12 months of treatment.GeneticsMajor Cytogenetic Response (MCyR), which was the primary endpoint for the CP-CML patient cohort in the PACE trial; 70% of the 64 patients with the T315I mutation achieved MCyR. In the PACE trial, 26% of the 449 patients experienced AOE.
Ponatinib Chemical Structure (Image source: medchemexpress.cn)
Iclusig is a kinase inhibitor targeting BCR-ABL1, an abnormal tyrosine kinase expressed in CML and Ph+ ALL. Iclusig is a targeted therapy developed using a computational and structure-based drug design platform.TumorIclusig is a drug specifically designed to inhibit the activity of BCR-ABL1 and its mutations. Iclusig can inhibit native BCR-ABL1 as well as all treatment-resistant mutations of BCR-ABL1, including the most resistant T315I mutation.
Iclusig is the only marketed TKI proven to be active against the T315I gatekeeper mutation of BCR-ABL1. This mutation is associated with resistance to all other marketed TKIs. Iclusig was approved in November 2016FDAFull Approval. This drug is indicated for: (1) adult patients with chronic-phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to at least two prior kinase inhibitors; (2) adult patients with accelerated-phase (AP) or blast-phase (BP) CML, and adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), for whom no other kinase inhibitor options are available; (3) adult patients with T315I mutation-positive CML (CP, AP, or BP) or T315I mutation-positive Ph+ ALL. Iclusig is not indicated nor recommended for the treatment of newlyDiagnosispatients with CP-CML.(Bioon.com)