CLINICAL TRIALS PROFILE FOR ASCIMINIB HYDROCHLORIDE

All Clinical Trials for ASCIMINIB HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03106779 ↗	Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs	Active, not recruiting	Novartis Pharmaceuticals	Phase 3	2017-10-26	The purpose of this pivotal study is to compare the efficacy of ABL001 with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs. Patients intolerant to the most recent TKI therapy must have BCR-ABL1 ratio > 0.1% IS at screening and patients failing their most recent TKI therapy must meet the definition of treatment failure as per the 2013 ELN guidelines. Patients with documented treatment failure while on bosutinib treatment will have the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.
NCT03578367 ↗	Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	Active, not recruiting	Novartis Pharmaceuticals	Phase 2	2018-11-22	To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)
NCT03605277 ↗	Pharmacokinetics Study of Asciminib in Subjects With Impaired Renal Function Compared to Matched Healthy Volunteers	Completed	Novartis Pharmaceuticals	Phase 1	2018-11-16	The purpose of this study is to characterize the pharmacokinetics (PK) and safety profile of asciminib following a single oral dose in adult subjects with renal impairment compared to a matched group of healthy subjects with normal renal function. The results will determine whether or not a dose adjustment should be recommended when treating patients with asciminib who have impaired renal function.
NCT03906292 ↗	Frontline Asciminib Combination in Chronic Phase CML	Recruiting	Ludwig-Maximilians - University of Munich	Phase 2	2019-08-19	Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.
NCT03906292 ↗	Frontline Asciminib Combination in Chronic Phase CML	Recruiting	Novartis Pharmaceuticals	Phase 2	2019-08-19	Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.
NCT03906292 ↗	Frontline Asciminib Combination in Chronic Phase CML	Recruiting	Prof. Dr. med. Andreas Hochhaus	Phase 2	2019-08-19	Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.
NCT03906292 ↗	Frontline Asciminib Combination in Chronic Phase CML	Recruiting	University of Jena	Phase 2	2019-08-19	Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.

Clinical Trial Conditions for ASCIMINIB HYDROCHLORIDE

Condition Name

Condition Name for ASCIMINIB HYDROCHLORIDE
Intervention	Trials
Chronic Myelogenous Leukemia	4
Chronic Myelogenous Leukemia - Chronic Phase	2
Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive	1
Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia	1

Condition MeSH

Condition MeSH for ASCIMINIB HYDROCHLORIDE
Intervention	Trials
Leukemia, Myelogenous, Chronic, BCR-ABL Positive	15
Leukemia	13
Leukemia, Myeloid	12
Philadelphia Chromosome	4

Clinical Trial Locations for ASCIMINIB HYDROCHLORIDE

Trials by Country

Trials by Country for ASCIMINIB HYDROCHLORIDE
Location	Trials
United States	24
Spain	9
Japan	7
Germany	6
Italy	5

Trials by US State

Trials by US State for ASCIMINIB HYDROCHLORIDE
Location	Trials
Texas	3
Georgia	2
Maryland	2
Illinois	2
Wisconsin	1

Clinical Trial Progress for ASCIMINIB HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for ASCIMINIB HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 3	7
Phase 2	7
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for ASCIMINIB HYDROCHLORIDE
Clinical Trial Phase	Trials
Not yet recruiting	7
Recruiting	6
Active, not recruiting	2

Clinical Trial Sponsors for ASCIMINIB HYDROCHLORIDE

Sponsor Name

Sponsor Name for ASCIMINIB HYDROCHLORIDE
Sponsor	Trials
Novartis Pharmaceuticals	12
H. Jean Khoury Cure CML Consortium	2
M.D. Anderson Cancer Center	1

Sponsor Type

Sponsor Type for ASCIMINIB HYDROCHLORIDE
Sponsor	Trials
Industry	13
Other	9
NIH	1

ASCIMINIB HYDROCHLORIDE Market Analysis and Financial Projection

Asciminib Hydrochloride: A Revolutionary Treatment for Chronic Myeloid Leukemia

Introduction

Asciminib hydrochloride, marketed as Scemblix, has emerged as a promising treatment for Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This article delves into the recent clinical trials, safety and efficacy profiles, market analysis, and future projections for this groundbreaking drug.

Clinical Trials Overview

ASC4FIRST Clinical Trial

The ASC4FIRST clinical trial, a phase 3 study, compared asciminib with the current standard-of-care tyrosine kinase inhibitors (TKIs) for newly diagnosed chronic phase CML. The trial involved 405 patients, with 201 receiving asciminib and 204 receiving either imatinib or a second-generation TKI. Key findings include:

• Efficacy: After 48 weeks, 68% of patients in the asciminib arm achieved a major molecular response (MMR) compared to 49% in the TKI arm. Additionally, 39% of patients in the asciminib arm achieved a deep molecular response, a significant indicator for potential treatment-free remission[1].

• Safety and Tolerability: The trial demonstrated that asciminib had a favorable safety profile, with fewer adverse events compared to traditional TKIs. Treatment was ongoing for 86% of patients receiving asciminib, highlighting its tolerability[1].

ASCEMBL Clinical Trial

The ASCEMBL trial focused on patients with Ph+ CML in chronic phase who had been previously treated with two or more TKIs. This multi-center, randomized trial compared asciminib with bosutinib, another third-line TKI.

• Efficacy: The trial showed that asciminib achieved a higher MMR rate at 24 weeks (25%) compared to bosutinib (13%). Asciminib also demonstrated a better safety profile, with fewer adverse events and longer treatment duration[4].

• Safety: The most common adverse effects associated with asciminib were thrombocytopenia and neutropenia, but overall, it exhibited a more favorable safety profile than bosutinib[3][4].

CABL001X2101 Clinical Trial

This trial evaluated asciminib in patients with the T315I mutation, a mutation that often confers resistance to other TKIs. The study found that 42% of patients achieved MMR by 24 weeks, and 49% by 96 weeks, when treated with asciminib 200 mg twice daily[4].

Mechanism of Action and Pharmacology

Asciminib hydrochloride is a potent, orally bioavailable BCR-ABL1 tyrosine kinase inhibitor with a novel mechanism of action. It specifically targets the ABL myristoyl pocket, which allows it to overcome resistance and intolerance to previously approved TKIs. This unique mechanism reduces the likelihood of point mutations in the ATP-site of the ABL1 kinase, a common cause of resistance to other inhibitors[2][5].

Safety Profile

Clinical trials have consistently shown that asciminib has a favorable safety profile compared to other TKIs. Common adverse reactions include upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. Laboratory abnormalities such as decreased platelet and neutrophil counts, and increased triglycerides and creatine kinase levels, have also been observed. However, these adverse effects are generally less severe and less frequent than those associated with other TKIs[3][4].

Market Analysis

Regulatory Approvals

Asciminib received accelerated approval from the FDA in October 2021 for patients with Ph+ CML in chronic phase who have been previously treated with two or more TKIs, including those with the T315I mutation. This approval was granted under the FDA's expedited programs, including priority review, breakthrough designation, fast track designation, and orphan drug designation[4].

Market Positioning

Given its superior efficacy and safety profile, asciminib is poised to become a significant player in the CML treatment market. It offers a new treatment option for patients who have failed or are intolerant to other TKIs, addressing a critical unmet need in this patient population.

Competitive Landscape

The CML treatment market is dominated by TKIs such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib. However, asciminib's unique mechanism of action and favorable safety profile position it as a competitive alternative, particularly for patients with resistance or intolerance to existing treatments[5].

Market Projections

Growth Potential

With its recent FDA approval and ongoing clinical trials, asciminib is expected to see significant growth in the coming years. The drug's ability to overcome resistance and its favorable safety profile are key drivers of this growth.

Patient Population

The target patient population for asciminib includes those with Ph+ CML in chronic phase who have been previously treated with two or more TKIs. This population is substantial, given the high incidence of resistance and intolerance to existing TKIs.

Revenue Projections

Given the strong clinical data and favorable regulatory environment, asciminib is projected to generate significant revenue. Novartis, the manufacturer, is expected to benefit from the drug's market performance, particularly as it gains wider acceptance and adoption among healthcare providers.

Future Directions

Long-Term Safety and Efficacy

Researchers will continue to follow participants in the clinical trials to understand the long-term safety profile of asciminib and to determine if achieving an MMR earlier continues to predict favorable outcomes. Additional studies will focus on overall survival, progression-free survival, and the potential for treatment-free remission[1].

Expanded Indications

There is potential for asciminib to be explored in other indications beyond Ph+ CML, given its novel mechanism of action. Future clinical trials may investigate its use in other types of leukemia or cancers where BCR-ABL1 is implicated.

Key Takeaways

• Superior Efficacy: Asciminib has demonstrated superior efficacy in achieving major and deep molecular responses compared to traditional TKIs.
• Favorable Safety Profile: Clinical trials have shown that asciminib has a better safety profile, with fewer adverse events and longer treatment duration.
• Market Potential: Asciminib is poised to become a significant player in the CML treatment market, addressing a critical unmet need for patients with resistance or intolerance to existing TKIs.
• Future Directions: Ongoing and future studies will focus on long-term safety, efficacy, and potential expanded indications.

FAQs

What is asciminib hydrochloride?

Asciminib hydrochloride, marketed as Scemblix, is a potent BCR-ABL1 tyrosine kinase inhibitor used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).

What are the key findings from the ASC4FIRST clinical trial?

The ASC4FIRST trial showed that asciminib achieved a higher major molecular response rate and a better safety profile compared to traditional TKIs for newly diagnosed CML patients[1].

How does asciminib compare to other TKIs in terms of safety?

Asciminib has been shown to have a more favorable safety profile, with fewer adverse events and longer treatment duration, compared to other TKIs like bosutinib[3][4].

What are the common adverse reactions associated with asciminib?

Common adverse reactions include upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea, along with laboratory abnormalities such as decreased platelet and neutrophil counts[4].

What are the future directions for asciminib research?

Future studies will focus on the long-term safety and efficacy of asciminib, as well as potential expanded indications beyond Ph+ CML[1].

How was asciminib approved by regulatory authorities?

Asciminib received accelerated approval from the FDA in October 2021 under the expedited programs, including priority review, breakthrough designation, fast track designation, and orphan drug designation[4].

Sources

1. Asciminib May Be Safer, More Effective Treatment Option for People with Newly Diagnosed Chronic Myeloid Leukemia. American Society of Clinical Oncology.
2. Asciminib Hydrochloride. FDA.
3. Asciminib (SCEMBLIX) National Drug Monograph October 2023. Department of Veterans Affairs.
4. FDA Approves Asciminib for Philadelphia Chromosome-Positive Chronic Myeloid Leukemia. FDA.
5. Australian Public Assessment Report for Scemblix. Therapeutic Goods Administration.