CLINICAL TRIALS PROFILE FOR PEXIDARTINIB HYDROCHLORIDE

All Clinical Trials for Pexidartinib Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01349036 ↗	A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma	Terminated	Plexxikon	Phase 2	2011-12-03	The objective of this study is to evaluate the response of subjects with recurrent glioblastoma to continuous therapy of PLX3397.
NCT01349036 ↗	A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma	Terminated	Daiichi Sankyo, Inc.	Phase 2	2011-12-03	The objective of this study is to evaluate the response of subjects with recurrent glioblastoma to continuous therapy of PLX3397.
NCT01525602 ↗	Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors	Completed	Plexxikon	Phase 1	2012-05-01	This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
NCT01525602 ↗	Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors	Completed	Daiichi Sankyo, Inc.	Phase 1	2012-05-01	This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
NCT01790503 ↗	A Phase 1b/2 Study of PLX3397 + Radiation Therapy + Temozolomide in Patients With Newly Diagnosed Glioblastoma	Completed	Plexxikon	Phase 1/Phase 2	2013-07-18	The study objectives are to assess the potential for PLX3397 to improve the efficacy of standard of care radiation therapy (RT) + temozolomide in patients with newly diagnosed glioblastoma (GBM).
NCT01790503 ↗	A Phase 1b/2 Study of PLX3397 + Radiation Therapy + Temozolomide in Patients With Newly Diagnosed Glioblastoma	Completed	Daiichi Sankyo, Inc.	Phase 1/Phase 2	2013-07-18	The study objectives are to assess the potential for PLX3397 to improve the efficacy of standard of care radiation therapy (RT) + temozolomide in patients with newly diagnosed glioblastoma (GBM).
NCT02371369 ↗	Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)	Completed	Daiichi Sankyo Inc.	Phase 3	2015-05-11	This is a Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug called pexidartinib for the treatment of certain tumors for which surgical removal could cause more harm than good. The main purpose of this study is to gather information about the investigational drug pexidartinib, which may help to treat tumors of pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS). The study consists of two parts with a follow-up period. In Part 1, eligible study participants will be assigned to receive either pexidartinib or matching placebo for 24 weeks. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. MRI scans will be used to evaluate the response of the tumors to the treatment. Some subjects, assigned to placebo in Part 1 transitioned to pexidartinib for Part 2. Then a protocol amendment was written to allow only pexidartinib patients to continue into Part 2. Part 2 is a long-term treatment phase in which all participants receive open-label pexidartinib. There was also a follow-up period added to Part 2.

Clinical Trial Conditions for Pexidartinib Hydrochloride

Condition Name

Condition Name for Pexidartinib Hydrochloride
Intervention	Trials
Tenosynovial Giant Cell Tumor	4
Gastrointestinal Stromal Tumor (GIST)	2
Melanoma	2
Tenosynovial Giant Cell Tumour	1

Condition MeSH

Condition MeSH for Pexidartinib Hydrochloride
Intervention	Trials
Giant Cell Tumors	4
Giant Cell Tumor of Tendon Sheath	4
Neoplasms	3
Gastrointestinal Stromal Tumors	3

Clinical Trial Locations for Pexidartinib Hydrochloride

Trials by Country

Trials by Country for Pexidartinib Hydrochloride
Location	Trials
United States	68
Korea, Republic of	6
Australia	5
Taiwan	4
Netherlands	3

Trials by US State

Trials by US State for Pexidartinib Hydrochloride
Location	Trials
New York	8
Massachusetts	7
California	7
Texas	6
Michigan	5

Clinical Trial Progress for Pexidartinib Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Pexidartinib Hydrochloride
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	2
Phase 2	2

Clinical Trial Status

Clinical Trial Status for Pexidartinib Hydrochloride
Clinical Trial Phase	Trials
Completed	11
Active, not recruiting	2
Recruiting	2

Clinical Trial Sponsors for Pexidartinib Hydrochloride

Sponsor Name

Sponsor Name for Pexidartinib Hydrochloride
Sponsor	Trials
Plexxikon	13
Daiichi Sankyo, Inc.	11
Daiichi Sankyo Co., Ltd.	4

Sponsor Type

Sponsor Type for Pexidartinib Hydrochloride
Sponsor	Trials
Industry	35
Other	2

Pexidartinib Hydrochloride: Clinical Trials Update, Market Analysis, and Projections

Introduction

Pexidartinib hydrochloride, marketed as Turalio, is a selective tyrosine kinase inhibitor developed by Daiichi Sankyo for the treatment of various conditions, most notably tenosynovial giant cell tumor (TGCT). Here, we delve into the current status of clinical trials, market analysis, and future projections for this drug.

Clinical Trials Update

Approved Indications

Pexidartinib hydrochloride is FDA-approved for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery[4][5].

Ongoing Clinical Trials

• Phase II Trials for Sarcomas: Pexidartinib hydrochloride is currently in Phase II clinical trials for the treatment of sarcomas. The success rate for Phase II drugs transitioning to Phase III for sarcomas is approximately 27% according to GlobalData's benchmarks[1].
• Phase 4 Study on Discontinuation and Rechallenge: A recent Phase 4 study evaluated the safety and efficacy of discontinuing and restarting pexidartinib in patients with TGCT. The study found that restarting pexidartinib was safe and effective, with patients achieving new disease stabilization and improvements in physical function without significant safety concerns[3].

Other Investigational Uses

Pexidartinib is being investigated for a wide range of conditions, including malignant peripheral nerve sheath tumors, rheumatoid arthritis, Alzheimer's disease, various types of cancer (such as Hodgkin lymphoma, prostate cancer, and non-small cell lung carcinoma), and other rare diseases like pigmented villonodular synovitis and gastrointestinal stromal tumors (GIST)[1][4].

Mechanism of Action and Pharmacology

Pexidartinib works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway, as well as other tyrosine kinases such as KIT and FLT3. This mechanism is crucial for its antitumor effects, particularly in conditions like TGCT where the CSF1 pathway is overactive[5].

Market Analysis

Current Market Position

Pexidartinib is the first systemic therapy approved for the treatment of TGCT, providing a significant market advantage in this niche. The drug is available through a special program called Turalio REMS (Risk Evaluation and Mitigation Strategy) due to its potential for liver toxicity[4].

Market Size and Growth

The market for rare disease treatments is growing, driven by increasing awareness, advances in diagnostic techniques, and the development of targeted therapies. Pexidartinib, being a first-in-class treatment for TGCT, holds a strong position in this market segment. However, its market size is limited by the rarity of the condition it treats.

Competitive Landscape

While pexidartinib is currently the only FDA-approved systemic therapy for TGCT, other treatments are being developed for similar conditions. The competitive landscape may evolve as new drugs enter the market, but pexidartinib's established position and ongoing clinical trials in other indications provide a strong foundation.

Projections and Future Outlook

Expansion into New Indications

Given its broad spectrum of activity against various tyrosine kinases, pexidartinib has the potential to be approved for multiple indications beyond TGCT. Successful outcomes in ongoing and future clinical trials could significantly expand its market reach and revenue potential.

Regulatory and Safety Considerations

The drug's safety profile, particularly its risk of liver toxicity, is closely monitored. The Turalio REMS program ensures that the benefits of the drug are balanced against its risks. Future regulatory approvals will depend on the continued demonstration of safety and efficacy in various patient populations[4].

Patient and Physician Acceptance

The Phase 4 study on discontinuation and rechallenge has provided valuable insights into the real-world use of pexidartinib, enhancing patient and physician confidence in the drug's safety and efficacy. This could lead to increased adoption and longer treatment durations, positively impacting market projections.

Key Statistics and Insights

• Approval Rate: Phase II drugs for sarcomas have a 27% phase transition success rate (PTSR) for progressing into Phase III[1].
• Patient Outcomes: In the Phase 4 study, 54.5% of patients who discontinued pexidartinib experienced disease progression, while those who restarted the drug achieved new disease stabilization and improvements in physical function[3].
• Market Growth: The global market for rare disease treatments is expected to grow significantly, driven by advances in targeted therapies and increasing awareness of rare conditions.

"Pexidartinib is the first systemic therapy approved for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery."[4]

Conclusion

Pexidartinib hydrochloride is a promising drug with a strong market position in the treatment of TGCT and potential for expansion into other indications. Ongoing and future clinical trials will be crucial in determining its full therapeutic potential and market impact.

Key Takeaways

• Approved Indication: Pexidartinib is FDA-approved for the treatment of symptomatic TGCT.
• Ongoing Trials: The drug is in Phase II trials for sarcomas and has been studied in a Phase 4 trial for discontinuation and rechallenge in TGCT patients.
• Mechanism of Action: It inhibits the CSF1/CSF1 receptor pathway and other tyrosine kinases.
• Market Position: It holds a strong position in the rare disease market, particularly for TGCT.
• Future Outlook: Potential expansion into new indications and continued safety monitoring are key factors in its future success.

FAQs

What is pexidartinib hydrochloride used for?

Pexidartinib hydrochloride is used for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery[4].

What is the current phase of clinical trials for pexidartinib in sarcomas?

Pexidartinib is currently in Phase II clinical trials for the treatment of sarcomas[1].

What were the findings of the Phase 4 study on discontinuation and rechallenge of pexidartinib?

The study found that restarting pexidartinib was safe and effective, with patients achieving new disease stabilization and improvements in physical function without significant safety concerns[3].

What is the mechanism of action of pexidartinib hydrochloride?

Pexidartinib works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway, as well as other tyrosine kinases such as KIT and FLT3[5].

Is pexidartinib hydrochloride available through a special program?

Yes, pexidartinib is available through a special program called Turalio REMS (Risk Evaluation and Mitigation Strategy) due to its potential for liver toxicity[4].

Sources

1. Pharmaceutical Technology: "Pexidartinib hydrochloride by Daiichi Sankyo for Sarcomas"
2. European Medicines Agency: "Turalio, INN-pexidartinib - European Medicines Agency"
3. PubMed: "A phase 4, multicenter, global clinical study to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with tenosynovial giant cell tumor"
4. National Cancer Institute: "Pexidartinib Hydrochloride - NCI"
5. DrugBank: "Pexidartinib: Uses, Interactions, Mechanism of Action - DrugBank"