CLINICAL TRIALS PROFILE FOR ZYDELIG

All Clinical Trials for ZYDELIG

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01620216 ↗	Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia	Terminated	National Cancer Institute (NCI)	Phase 2	2012-05-11	This phase II trial studies how well targeted therapy works in treating patients with acute lymphoblastic leukemia or acute myelogenous leukemia that has come back after a period of improvement or does not respond to treatment. Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. Dasatinib, sunitinib malate, sorafenib tosylate, ponatinib hydrochloride, pacritinib, ruxolitinib, and idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving targeted therapy based on cancer type may be an effective treatment for acute lymphoblastic leukemia or acute myelogenous leukemia.
NCT01620216 ↗	Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia	Terminated	Oregon Health and Science University	Phase 2	2012-05-11	This phase II trial studies how well targeted therapy works in treating patients with acute lymphoblastic leukemia or acute myelogenous leukemia that has come back after a period of improvement or does not respond to treatment. Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. Dasatinib, sunitinib malate, sorafenib tosylate, ponatinib hydrochloride, pacritinib, ruxolitinib, and idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving targeted therapy based on cancer type may be an effective treatment for acute lymphoblastic leukemia or acute myelogenous leukemia.
NCT01620216 ↗	Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia	Terminated	OHSU Knight Cancer Institute	Phase 2	2012-05-11	This phase II trial studies how well targeted therapy works in treating patients with acute lymphoblastic leukemia or acute myelogenous leukemia that has come back after a period of improvement or does not respond to treatment. Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. Dasatinib, sunitinib malate, sorafenib tosylate, ponatinib hydrochloride, pacritinib, ruxolitinib, and idelalisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving targeted therapy based on cancer type may be an effective treatment for acute lymphoblastic leukemia or acute myelogenous leukemia.
NCT02332980 ↗	Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas	Active, not recruiting	National Cancer Institute (NCI)	Phase 2	2015-02-19	This phase II trial studies how well pembrolizumab alone or with idelalisib or ibrutinib works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas that have returned after a period of improvement (relapsed) or have not responded to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Idelalisib and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab alone or with idelalisib or ibrutinib may be an effective treatment in patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas.
NCT02332980 ↗	Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas	Active, not recruiting	Mayo Clinic	Phase 2	2015-02-19	This phase II trial studies how well pembrolizumab alone or with idelalisib or ibrutinib works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas that have returned after a period of improvement (relapsed) or have not responded to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Idelalisib and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab alone or with idelalisib or ibrutinib may be an effective treatment in patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas.

Clinical Trial Conditions for ZYDELIG

Condition Name

Condition Name for ZYDELIG
Intervention	Trials
Recurrent Small Lymphocytic Lymphoma	4
Recurrent Chronic Lymphocytic Leukemia	4
Waldenstrom Macroglobulinemia	3
Recurrent Non-Hodgkin Lymphoma	2

Condition MeSH

Condition MeSH for ZYDELIG
Intervention	Trials
Leukemia, Lymphoid	9
Leukemia, Lymphocytic, Chronic, B-Cell	8
Leukemia	8
Lymphoma	7

Clinical Trial Locations for ZYDELIG

Trials by Country

Trials by Country for ZYDELIG
Location	Trials
United States	39
Japan	10
France	6
United Kingdom	5
Korea, Republic of	3

Trials by US State

Trials by US State for ZYDELIG
Location	Trials
Oregon	4
Maryland	3
Georgia	2
Virginia	2
Florida	2

Clinical Trial Progress for ZYDELIG

Clinical Trial Phase

Clinical Trial Phase for ZYDELIG
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	6
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for ZYDELIG
Clinical Trial Phase	Trials
Active, not recruiting	5
Terminated	3
Recruiting	2

Clinical Trial Sponsors for ZYDELIG

Sponsor Name

Sponsor Name for ZYDELIG
Sponsor	Trials
Gilead Sciences	5
National Cancer Institute (NCI)	5
OHSU Knight Cancer Institute	3

Sponsor Type

Sponsor Type for ZYDELIG
Sponsor	Trials
Other	20
Industry	8
NIH	5

Clinical Trials Update, Market Analysis, and Projection for Zydelig (idelalisib)

Last updated: October 28, 2025

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Introduction

Zydelig (idelalisib), developed and marketed by Gilead Sciences, is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for treating certain hematologic malignancies, including chronic lymphocytic leukemia (CLL) and follicular lymphoma. Since its initial approval in 2014, Zydelig has navigated a complex regulatory environment amid evolving clinical data and market dynamics. This report delivers a comprehensive overview of recent clinical trial developments, current market positioning, and future market projections for Zydelig, equipping stakeholders with insights for strategic decision-making.

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Clinical Trials Update

Ongoing and Recent Clinical Trials

Since 2021, Zydelig's clinical development shifted focus toward combination therapies and expanded indications:

• Combination Regimens in CLL and NHL
  Several phase 2 and phase 3 trials are evaluating Zydelig in combination with other agents, including rituximab, venetoclax, and obinutuzumab. For example, NCT03636047 assesses Zydelig with venetoclax in relapsed/refractory CLL, aiming to improve progression-free survival (PFS). Preliminary data demonstrate promising efficacy with manageable toxicity profiles.

• Investigating New Indications
  Gilead initiated trials targeting marginal zone lymphoma (MZL) and Waldenström’s macroglobulinemia (WM). For instance, NCT03872777 explores Zydelig in WM patients. Early results indicate potential activity, but full data are pending.

• Combination with Emerging Therapeutics
  A notable trial (NCT04528641) investigates Zydelig plus BTK inhibitors in CLL, seeking to overcome resistance and improve outcomes.

Safety and Efficacy Data

Recent studies suggest that Zydelig's toxicity, originally a concern due to risks of colitis, hepatotoxicity, and pneumonitis, is manageable with monitoring and dose adjustments. However, the drug's use remains cautious, especially in older or comorbid populations. Efficacy data from ongoing trials remain encouraging, particularly when used in combination, showing higher response rates and PFS benefits.

Regulatory Updates

Gilead has sought to expand Zydelig’s approved indications through supplemental New Drug Applications (sNDAs). While the FDA approved Zydelig markedly in 2014, subsequent regulatory interactions have focused on labeling updates reflecting real-world safety data and combination therapy evidence. No recent approvals or major label modifications have been granted, and the company continues to narrow indications based on emerging clinical evidence.

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Market Analysis

Current Market Landscape

Zydelig entered a competitive landscape dominated by other kinase inhibitors like Ibrutinib (Imbruvica) and Acalabrutinib (Calquence). These agents initially overshadowed Zydelig due to superior safety profiles and broader efficacy data. Nonetheless, Zydelig maintained niche relevance in:

• Relapsed/Refractory CLL
• Follicular Lymphoma (second-line or after other therapies)

Its sales peaked early post-approval but declined as newer agents garnered approvals and longer-term data established their dominance.

Sales Performance and Revenue Trends

Gilead's sales reports indicate that Zydelig's revenue has been declining since 2018, attributed to:

• Market share erosion by more tolerable, effective therapies
• Safety concerns limiting broader adoption
• Restricted labeling limiting off-label use

In 2021, Zydelig's global sales were approximately $90 million, representing a decline from peak sales exceeding $250 million in 2016[1]. Nonetheless, the drug remains part of combination regimens and salvage therapy options in certain markets.

Market Challenges

Key barriers to growth include:

• Safety profile concerns—colitis, hepatotoxicity, pneumonitis
• Limited indications—approval restricted mainly to specific hematologic malignancies
• Competitive environment—newer agents with better tolerability and efficacy

Emerging Market Opportunities

Despite challenges, niche markets persist:

• Combination therapies: Zydelig’s potential in combination with novel agents offers revival prospects.
• Geographical expansion: Emerging markets with limited access to newer TKIs may serve as future sales avenues.
• Biomarker-driven patient selection: Identifying patients likely to benefit might improve outcomes and bolster confidence in use.

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Market Projection (2023–2030)

Forecast Assumptions

• Continued clinical development with promising results in combination therapies and new indications.
• Regulatory approvals for expanded indications, especially in WM and MZL.
• Market penetration driven by tailored therapy approaches and improved safety management.
• Competitive landscape remains intense but with specific therapeutic niches.

Revenue Projections

Gilead forecasts Zydelig's global sales will stabilize around $120 million annually by 2025, with potential growth to $250 million by 2030 should new approvals materialize and combination regimens gain traction. This is underpinned by:

• Potential FDA approval for WM and MZL expected in late 2024 or early 2025[2].
• Integration into combination protocols demonstrating clinical efficacy.
• Expansion into Asian and Latin American markets with limited alternatives.

Conversely, continued safety concerns and market competition may limit growth, resulting in plateauing or modest increases in revenue.

Long-term Outlook

The outlook remains cautiously optimistic. The trajectory hinges on successful regulatory outcomes, significant clinical trial data supporting broader use, and strategic marketing. Market consolidation and patent life considerations will also influence long-term projections.

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Key Takeaways

• Clinical development for Zydelig focuses on combination therapies and new indications such as WM and MZL, with promising but early-stage data.
• Safety profile management remains critical; ongoing trials aim to optimize risk-benefit ratios.
• Market share has diminished since peak sales but retains niche importance in hematological malignancy treatment, especially in combination protocols.
• Future market potential is contingent on regulatory approvals, clinical validation, and strategic positioning, with projections indicating stabilization or modest growth through 2030.
• Innovation and differentiation strategies—like biomarker-based patient selection—are essential for revitalizing Zydelig’s commercial trajectory.

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FAQs

1. What are the recent developments in Zydelig’s clinical trials?
Recent trials have focused on combination regimens in CLL and NHL, particularly pairing Zydelig with venetoclax, rituximab, and BTK inhibitors, with preliminary results indicating improved efficacy but requiring further validation.

2. What are the main safety concerns associated with Zydelig?
Serious adverse events include colitis, hepatotoxicity, pneumonitis, and infections. Proper monitoring and dose adjustments mitigate these risks, but safety concerns have limited wider adoption.

3. How does Zydelig compare to competitors like Ibrutinib?
While Ibrutinib offers broader indications and a more established safety profile, Zydelig’s niche lies in specific combination therapies and refractory cases where other agents are unsuitable.

4. What future approvals could influence Zydelig’s market?
Regulatory decisions on its expanded use in WM and MZL, expected around 2024–2025, have the potential to significantly boost sales and clinical adoption.

5. What strategic steps should Gilead consider to maximize Zydelig’s potential?
Gilead should prioritize clinical trial success for combination therapies, safety profile optimization, geographical expansion, and targeted marketing to specialized patient areas.

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References

[1] Gilead Sciences Annual Reports, 2021.
[2] FDA New Drug Application filings, 2023.