CLINICAL TRIALS PROFILE FOR IBRUTINIB

505(b)(2) Clinical Trials for IBRUTINIB

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT02877225 ↗	Study to Assess the Bioequivalence of Ibrutinib 140 Milligram (mg) Tablet to 140 mg IMBRUVICA Capsule	Completed	Janssen Research & Development, LLC	Phase 1	2016-08-29	The purpose of this study is to demonstrate the bioequivalence (BE) of a new formulation of ibrutinib to the marketed Imbruvica formulation in healthy adults under fasted conditions.
New Formulation	NCT02841150 ↗	Study to Assess the Bioequivalence of Ibrutinib 560- Milligram (mg) Tablet to Four 140 -mg IMBRUVICA Capsules	Completed	Janssen Research & Development, LLC	Phase 1	2016-06-01	The purpose of this study is to demonstrate the bioequivalence (BE) of a new formulation of ibrutinib to the marketed Imbruvica formulation in healthy adults under fasted conditions.
New Combination	NCT02436707 ↗	Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma	Recruiting	Janssen, LP	Phase 2	2015-05-05	The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.
New Combination	NCT02436707 ↗	Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma	Recruiting	Karyopharm Therapeutics Inc	Phase 2	2015-05-05	The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.
New Combination	NCT02436707 ↗	Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma	Recruiting	Roche Pharma AG	Phase 2	2015-05-05	The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.
New Combination	NCT02436707 ↗	Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma	Recruiting	Canadian Cancer Trials Group	Phase 2	2015-05-05	The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.

All Clinical Trials for IBRUTINIB

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01478581 ↗	Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma	Completed	Pharmacyclics LLC.	Phase 2	2012-03-01	The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM)
NCT01325701 ↗	Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma	Completed	Pharmacyclics LLC.	Phase 2	2011-05-01	The purpose of this study is to evaluate the efficacy of ibrutinib (PCI-32765) in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).
NCT01236391 ↗	Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)	Completed	Janssen Pharmaceuticals	Phase 2	2011-02-01	The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL. The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.
NCT01236391 ↗	Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)	Completed	Pharmacyclics LLC.	Phase 2	2011-02-01	The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL. The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.
NCT01217749 ↗	Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL	Completed	Ohio State University	Phase 1/Phase 2	2010-12-01	The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases
NCT01217749 ↗	Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL	Completed	Pharmacyclics LLC.	Phase 1/Phase 2	2010-12-01	The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases

Clinical Trial Conditions for IBRUTINIB

Condition Name

Condition Name for IBRUTINIB
Intervention	Trials
Chronic Lymphocytic Leukemia	70
Mantle Cell Lymphoma	39
Small Lymphocytic Lymphoma	33
Waldenstrom Macroglobulinemia	20

Condition MeSH

Condition MeSH for IBRUTINIB
Intervention	Trials
Lymphoma	187
Leukemia, Lymphoid	131
Leukemia, Lymphocytic, Chronic, B-Cell	131
Leukemia	121

Clinical Trial Locations for IBRUTINIB

Trials by Country

+

−

Trials by Country for IBRUTINIB
Location	Trials
France	90
Spain	90
United Kingdom	87
Italy	87
Australia	80

Trials by US State

+

−

Trials by US State for IBRUTINIB
Location	Trials
California	99
New York	93
Texas	91
Ohio	80
New Jersey	65

Clinical Trial Progress for IBRUTINIB

Clinical Trial Phase

Clinical Trial Phase for IBRUTINIB
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	44
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for IBRUTINIB
Clinical Trial Phase	Trials
Active, not recruiting	101
Recruiting	100
Completed	75

Clinical Trial Sponsors for IBRUTINIB

Sponsor Name

Sponsor Name for IBRUTINIB
Sponsor	Trials
Pharmacyclics LLC.	85
National Cancer Institute (NCI)	75
Janssen Research & Development, LLC	43

Sponsor Type

Sponsor Type for IBRUTINIB
Sponsor	Trials
Industry	315
Other	294
NIH	81

Ibrutinib: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to Ibrutinib

Ibrutinib, marketed under the brand name Imbruvica, is a groundbreaking kinase inhibitor that has revolutionized the treatment of various B-cell malignancies, including chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia, and several types of lymphoma. Here, we delve into the latest clinical trial updates, market analysis, and future projections for this pivotal drug.

Clinical Trials Update

CAPTIVATE Study

The CAPTIVATE study, a Phase 2 trial, has provided significant insights into the efficacy of ibrutinib in combination with venetoclax as a first-line treatment for CLL patients, including those with high-risk disease. With a 5.5-year follow-up, the study demonstrated sustained clinical benefit, showing a meaningful progression-free survival (PFS) in both the overall population and in patients with high-risk genomic features[1].

• Fixed Duration Regimen: Patients received three cycles of ibrutinib lead-in followed by 12 cycles of ibrutinib and venetoclax, with the primary endpoint being the complete remission rate.
• MRD-Guided Cohort: After completing the treatment, patients with confirmed undetectable minimal residual disease (uMRD) were randomly assigned to either placebo or continuous ibrutinib, with the primary endpoint being one-year disease-free survival.

E1912 Trial

The E1912 trial, a landmark study, compared the efficacy of ibrutinib-rituximab (IR) therapy to the traditional fludarabine, cyclophosphamide, and rituximab (FCR) regimen in CLL patients. With a median follow-up of 5.8 years, the trial showed superior PFS and overall survival (OS) for the IR arm compared to FCR[3].

• Long-Term Follow-Up: The updated results indicated that 60.5% of patients on IR continued ibrutinib, with progression being uncommon among those who remained on treatment.
• Tolerability: The study highlighted the long-term tolerability of single-agent ibrutinib, with a median time from ibrutinib discontinuation to disease progression or death being 25 months for those who discontinued treatment for reasons other than progression.

RESONATE-2 Study

The RESONATE-2 study, a Phase 3 trial, evaluated the efficacy and safety of ibrutinib as a single-agent therapy in previously untreated CLL patients aged 65 years or older. The final analysis, presented at the 2024 European Hematology Association (EHA) Congress, confirmed a sustained progression-free and overall survival benefit with up to 10 years of follow-up[4].

• Longest Follow-Up Data: This study provided the longest-term outcomes and safety data ever reported for a monotherapy BTK inhibitor, with a median PFS of 8.9 years.
• Comparative Survival: The pooled analysis of three Phase 3 studies showed that treatment with ibrutinib has the potential to achieve comparable overall survival to the general European population.

Market Analysis

Global Market Size and Growth

The ibrutinib market is experiencing robust growth driven by increasing incidence of blood cancers and advancements in healthcare infrastructure. As of 2023, the market size was valued at USD 11.83 billion and is projected to reach USD 61.88 billion by 2030, registering a CAGR of 23.10% from 2024 to 2030[5].

• Increasing Demand: The rising number of cancer patients globally and the expanding healthcare infrastructure are key drivers of the market.
• Generic Developments: Several market players, including Johnson & Johnson, Pfizer, and Bluepharma, are involved in developing generic versions of ibrutinib, which is expected to further drive market growth.

China Market

In China, the sales value of ibrutinib has seen significant growth since its introduction. From CNY 48,600 in 2017 to CNY 345.5 million in 2020, the market experienced a CAGR of 1823% during this period. Despite a slowdown due to the COVID-19 pandemic, the market is expected to recover and grow from 2021 to 2025 due to price reductions and market expansion[2].

• Approved Indications: Ibrutinib has three approved indications in China, with all of them included in the national medical insurance catalog, enhancing its usage rate.
• Competitive Landscape: The emergence of other BTK inhibitors may lead to price decreases, further boosting sales.

Market Projections

Future Growth Drivers

The ibrutinib market is poised for continued growth driven by several factors:

• Increasing Incidence of Blood Cancers: According to the American Cancer Society, the incidence of blood cancers such as leukemia continues to rise, driving demand for effective treatments like ibrutinib[5].
• Expanding Indications: Ibrutinib is being explored for additional indications, such as mantle cell lymphoma and diffuse large B-cell lymphoma, which will expand its market reach.
• Generic and Biosimilar Entries: The entry of generic and biosimilar versions is expected to increase accessibility and affordability, further driving market growth.

Geographical Expansion

Ibrutinib is approved in over 100 countries and has been used to treat nearly 300,000 patients worldwide. Its inclusion in the World Health Organization’s Model Lists of Essential Medicines (EML) in 2021 underscores its global importance and potential for further expansion into emerging markets[1][4].

Key Takeaways

• Clinical Efficacy: Ibrutinib has demonstrated sustained clinical benefits in various clinical trials, including the CAPTIVATE, E1912, and RESONATE-2 studies.
• Market Growth: The global ibrutinib market is expected to grow significantly, driven by increasing demand, expanding indications, and the entry of generic and biosimilar versions.
• Global Reach: Ibrutinib is widely approved and used globally, with a strong potential for further expansion into emerging markets.

FAQs

What are the primary indications for ibrutinib?

Ibrutinib is primarily used to treat chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia, and several types of lymphoma, including mantle cell lymphoma and marginal zone lymphoma[5].

How does ibrutinib work?

Ibrutinib blocks the Bruton’s tyrosine kinase (BTK) protein, which is essential for the proliferation and survival of abnormal B-cells, thereby inhibiting the spread of cancer cells[1][4].

What are the key findings from the CAPTIVATE study?

The CAPTIVATE study demonstrated sustained clinical benefit of the fixed-duration combination of ibrutinib and venetoclax as a first-line treatment for CLL patients, including those with high-risk disease, with a clinically meaningful PFS at 5.5 years of follow-up[1].

How does the E1912 trial compare ibrutinib-rituximab to traditional FCR therapy?

The E1912 trial showed that ibrutinib-rituximab therapy has superior PFS and OS compared to FCR, with a median follow-up of 5.8 years, and highlighted the long-term tolerability of single-agent ibrutinib[3].

What are the projections for the global ibrutinib market?

The global ibrutinib market is expected to reach USD 61.88 billion by 2030, growing at a CAGR of 23.10% from 2024 to 2030, driven by increasing demand and expanding indications[5].

Sources

1. Janssen-Cilag International NV. Updated Phase 2 CAPTIVATE study results demonstrate sustained clinical benefit of fixed-duration IMBRUVICA (ibrutinib) in combination with venetoclax as first-line treatment for patients with chronic lymphocytic leukaemia. Press Release, June 14, 2024.
2. GlobeNewswire. China Ibrutinib Markets, 2016-2020 & 2021-2025: A BTK Inhibitor Used to Treat B-cell Carcinomas. May 21, 2021.
3. American Society of Hematology. Long-term outcomes for ibrutinib-rituximab and updated results of the E1912 trial. Blood, July 14, 2022.
4. Janssen-Cilag International NV. Findings from landmark RESONATE-2 study confirm sustained survival benefit of IMBRUVICA (ibrutinib) for first-line chronic lymphocytic leukaemia treatment with up to 10 years follow-up. Press Release, June 14, 2024.
5. Next MSC. Ibrutinib Market Size and Share | Statistics – 2030. Report, 2023.