CLINICAL TRIALS PROFILE FOR PONATINIB HYDROCHLORIDE

All Clinical Trials for Ponatinib Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00660920 ↗	Safety Study of AP24534 to Treat Chronic Myelogenous Leukemia (CML) and Other Hematological Malignancies	Completed	Ariad Pharmaceuticals	Phase 1	2008-06-01	The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
NCT01207440 ↗	Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	Completed	Ariad Pharmaceuticals	Phase 2	2010-09-30	The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the (T)hreonine-315-(I)soleucine (T315I) mutation.
NCT01424982 ↗	Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia	Recruiting	Ariad Pharmaceuticals	Phase 2	2011-10-05	This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.
NCT01424982 ↗	Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia	Recruiting	M.D. Anderson Cancer Center	Phase 2	2011-10-05	This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.
NCT01549548 ↗	Compassionate Use Ponatinib	No longer available	Ariad Pharmaceuticals		1969-12-31	The main purpose of this protocol is to provide expanded access to the study drug (Ponatinib/AP24534) for people with imatinib-, dasatinib-, and nilotinib- resistant/intolerant Philadelphia Chromosome Positive (Ph+) Leukemias. The other purpose of this protocol is to monitor the safety of the study drug in people with Ph+ Leukemias that have not responded to prior treatment.
NCT01549548 ↗	Compassionate Use Ponatinib	No longer available	OHSU Knight Cancer Institute		1969-12-31	The main purpose of this protocol is to provide expanded access to the study drug (Ponatinib/AP24534) for people with imatinib-, dasatinib-, and nilotinib- resistant/intolerant Philadelphia Chromosome Positive (Ph+) Leukemias. The other purpose of this protocol is to monitor the safety of the study drug in people with Ph+ Leukemias that have not responded to prior treatment.

Clinical Trial Conditions for Ponatinib Hydrochloride

Condition Name

Condition Name for Ponatinib Hydrochloride
Intervention	Trials
Acute Lymphoblastic Leukemia	10
Chronic Myeloid Leukemia	9
Leukemia	8
Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive	6

Condition MeSH

Condition MeSH for Ponatinib Hydrochloride
Intervention	Trials
Leukemia	45
Leukemia, Myeloid	32
Leukemia, Myelogenous, Chronic, BCR-ABL Positive	29
Precursor Cell Lymphoblastic Leukemia-Lymphoma	28

Clinical Trial Locations for Ponatinib Hydrochloride

Trials by Country

Trials by Country for Ponatinib Hydrochloride
Location	Trials
United States	187
France	28
Italy	21
China	21
Japan	19

Trials by US State

Trials by US State for Ponatinib Hydrochloride
Location	Trials
Texas	19
Oregon	12
California	10
Maryland	9
Michigan	9

Clinical Trial Progress for Ponatinib Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Ponatinib Hydrochloride
Clinical Trial Phase	Trials
Phase 3	5
Phase 2/Phase 3	1
Phase 2	38

Clinical Trial Status

Clinical Trial Status for Ponatinib Hydrochloride
Clinical Trial Phase	Trials
Recruiting	26
Completed	10
Active, not recruiting	8

Clinical Trial Sponsors for Ponatinib Hydrochloride

Sponsor Name

Sponsor Name for Ponatinib Hydrochloride
Sponsor	Trials
Ariad Pharmaceuticals	16
National Cancer Institute (NCI)	10
M.D. Anderson Cancer Center	9

Sponsor Type

Sponsor Type for Ponatinib Hydrochloride
Sponsor	Trials
Other	56
Industry	32
NIH	11

Ponatinib Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

Ponatinib hydrochloride, marketed as Iclusig, is a tyrosine kinase inhibitor (TKI) developed by Takeda Pharmaceuticals USA, Inc. It has been approved for various indications related to leukemia and is under ongoing clinical development for other cancer types. Here, we will delve into the recent clinical trials, market analysis, and future projections for ponatinib hydrochloride.

Clinical Trials Update

Recent Approval for Ph+ ALL

On March 19, 2024, the FDA granted accelerated approval to ponatinib in combination with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)[1].

• The efficacy was evaluated in the PhALLCON trial, a randomized, active-controlled, multicenter, open-label study involving 245 adult patients. Patients received either ponatinib 30 mg orally once daily or imatinib 600 mg orally once daily, both with chemotherapy. The trial showed a significant difference in the minimal residual disease (MRD)-negative complete remission (CR) rate at the end of induction, with 30% in the ponatinib arm versus 12% in the imatinib arm[1].

Ongoing and Completed Trials

Ponatinib is also under clinical development for other indications, including Acute Myelocytic Leukemia (AML) and various other cancers.

• In the context of AML, ponatinib hydrochloride is currently in Phase II clinical trials. According to GlobalData, Phase II drugs for AML have a 30% phase transition success rate (PTSR) for progressing into Phase III[5].

• Another trial, identified by the EudraCT number 2019-002549-39, was prematurely ended. This trial was part of a Paediatric Investigation Plan and involved various phases of human pharmacology and therapeutic exploratory studies[4].

Market Analysis

Current Market Size and Growth

The global market for ponatinib drugs was estimated to be worth US$ 592 million in 2023. It is forecasted to grow to US$ 902.8 million by 2030, with a compound annual growth rate (CAGR) of 6.4% during the forecast period of 2024-2030[2].

Key Players

The main player in the ponatinib drugs market is ARIAD Pharmaceuticals, although Takeda Pharmaceuticals USA, Inc. is the current marketer of Iclusig following the acquisition of ARIAD Pharmaceuticals[2].

Market Segmentation

The market is segmented by type (45mg and 15mg formulations) and application (Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL))[2].

Indications and Usage

Approved Indications

Ponatinib hydrochloride is approved for the treatment of adult patients with:

• Chronic phase (CP), accelerated phase (AP), or blast phase (BP) chronic myeloid leukemia (CML)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
• CML or Ph+ ALL with the T315I mutation or those who are resistant or intolerant to other TKI therapies[3][5].

Dosage and Administration

The recommended dose of ponatinib is 30 mg orally once daily, with a reduction to 15 mg once daily upon achievement of MRD-negative CR at the end of induction. It is administered in combination with chemotherapy for up to 20 cycles until loss of response or unacceptable toxicity[1].

Safety Profile

Adverse Reactions

The most common adverse reactions associated with ponatinib include hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias[1].

Risk Management

To manage the serious risks associated with ponatinib, a Controlled Distribution Program has been instituted, which includes mandatory prescriber certification and a patient informed consent process. Safety monitoring is ongoing, and further evaluation will be conducted based on the submission of requested studies[3].

Market Projections

Growth Drivers

The growth of the ponatinib market is driven by several factors, including the increasing incidence of leukemia, the efficacy of ponatinib in treating resistant or intolerant cases, and the expanding indications for its use.

Challenges

Despite the positive outlook, the market faces challenges such as the high cost of the drug, potential side effects, and the need for stringent safety monitoring. Additionally, the competition from other TKIs and emerging therapies could impact market growth.

Future Development

Pipeline Indications

Ponatinib is under development for various other cancer types, including relapsed or refractory T-cell acute lymphoblastic leukemia, pulmonary tumor thrombotic microangiopathy, acute myelocytic leukemia (AML), advanced biliary cancer, lung cancer, and several other solid tumors[5].

Likelihood of Approval

GlobalData's report assesses the likelihood of approval for ponatinib in new indications based on historical drug development data. The drug-specific phase transition success rate and likelihood of approval scores are critical in predicting its future market potential[5].

Key Takeaways

• Accelerated Approval: Ponatinib has been granted accelerated approval for newly diagnosed Ph+ ALL in combination with chemotherapy.
• Market Growth: The global market for ponatinib is projected to grow from US$ 592 million in 2023 to US$ 902.8 million by 2030.
• Safety Profile: Ponatinib has a notable safety profile with common adverse reactions that require close monitoring.
• Expanding Indications: The drug is under development for several other cancer types, which could further expand its market.
• Risk Management: A Controlled Distribution Program is in place to manage the serious risks associated with ponatinib.

FAQs

What is ponatinib hydrochloride used for?

Ponatinib hydrochloride is used for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), especially in cases resistant or intolerant to other TKI therapies[3].

What is the current market size of ponatinib drugs?

The global market for ponatinib drugs was estimated to be worth US$ 592 million in 2023[2].

What is the projected growth rate of the ponatinib market?

The market is forecasted to grow at a CAGR of 6.4% from 2024 to 2030, reaching US$ 902.8 million by 2030[2].

What are the common adverse reactions associated with ponatinib?

Common adverse reactions include hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, and several others[1].

Is ponatinib under development for other cancer types?

Yes, ponatinib is under development for various other cancer types, including AML, advanced biliary cancer, lung cancer, and several solid tumors[5].

What is the likelihood of approval for ponatinib in new indications?

The likelihood of approval is assessed based on historical drug development data, with Phase II drugs for AML having a 30% phase transition success rate[5].

Sources

1. FDA: FDA grants accelerated approval to ponatinib with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)[1].
2. Valuates Reports: Ponatinib Drugs - Market, Report Size, Worth, Revenue, Growth[2].
3. Health Canada: Regulatory Decision Summary for ICLUSIG[3].
4. EU Clinical Trials Register: EU Clinical Trials Register - Ponatinib-1501[4].
5. Pharmaceutical Technology: Ponatinib hydrochloride by Takeda Pharmaceutical for Acute Myelocytic Leukemia (AML, Acute Myeloblastic Leukemia)[5].