CLINICAL TRIALS PROFILE FOR FOSTAMATINIB DISODIUM

All Clinical Trials for Fostamatinib Disodium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00706342 ↗	Pilot Study of Fostamatinib Disodium/R935788 for the Treatment of Adult Refractory Immune Thrombocytopenic Purpura (ITP)	Completed	Rigel Pharmaceuticals	Phase 2	2007-01-01	The purpose of this study is to determine whether Fostamatinib Disodium is safe and effective in the treatment of Adult Refractory Immune Thrombocytopenic Purpura (ITP).
NCT00798096 ↗	Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma	Completed	Rigel Pharmaceuticals	Phase 2	2009-03-01	Patients meeting specific inclusion and exclusion criteria will be enrolled in two stages, 19 patients in Stage 1 and 36 patients in Stage 2. Stage 2 will enroll if 4 or more patients exhibit a response at Week 8 or later in the study. All enrolled patients will be treated with Fostamatinib Disodium until disease progression. Efficacy will be assessed by tumor measurements using CT and PET (when indicated) scans and physical exam at baseline, and scans and physical exam of all disease-involved areas every 8 weeks until progression. Safety will be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All patients will have a follow-up visit 30 days following last study drug treatment. Blood samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol defined intervals.
NCT00923481 ↗	A Broad Multi-histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-small Cell Lung, Head and Neck Hepatocellular and Renal Cell Carcinomas, and Pheochromocytoma and Thyroid Tumors (Multi-	Completed	National Cancer Institute (NCI)	Phase 2	2009-04-01	Background: - The drug R935788 (fostamatanib disodium) is a kinase inhibitor (i.e., it interferes with cell communication and growth and may prevent tumor growth). - R935788 has shown promising activity in NCI-60 (a panel of 60 diverse human cancer cell lines) against colon cancer, non-small cell lung cancer, and renal cell carcinoma cell lines, as well as in two renal cell xenograft models. - This is an open-label, Phase II study of R935788. Phase I studies in patients with immune thrombocytopenic purpura, rheumatoid arthritis, and lymphoma have demonstrated safety with a continuous dosing schedule, and a maximum tolerated dose has been established. Objectives: - To test an experimental drug called R935788 (fostamatinib disodium) for its ability to stop cancer growth signals, thus slowing the growth of cancer cells in laboratory testing. - To determine the clinical response of R935788 administered orally twice a day on a continuous schedule in patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer, hepatocellular, carcinoma of the head and neck, and renal cell carcinoma. - To evaluate the effects, safety, and biochemical response of R935788 therapy. Eligibility: - Patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer (excluding squamous cell histology), hepatocellular cancer, carcinoma of the head and neck, and renal cell carcinoma whose disease has progressed after any therapy or who have no acceptable standard treatment options. - Patients must have recovered from toxicities of prior therapies to at least eligibility levels. - Patients who have received radiation or chemotherapy within 4 weeks of study enrollment are not eligible. - Women who are pregnant or breastfeeding are not eligible. Design: - Researchers will conduct the following tests and procedures during the study: - Clinic visits with a physical exam, including vital signs and blood pressure, every other week during cycle 1, and once a month starting with cycle 2. - Blood will be drawn weekly during cycle 1, every other week during cycle 2, and once a month starting with cycle 3; urine tests will be conducted depending on results of blood tests. - Imaging tests, such as computed tomography (CT) scans (a series of x-rays) or ultrasound (an examination using sound waves), will be done every 8 weeks while the patient is receiving R935788. - R935788 will be administered orally twice a day for 28 days (one cycle). Imaging studies will be obtained every two cycles. Patients will fill in a diary to show when they took the medication and to note any side effects. The 28-day treatment cycle will be repeated as long as the patient is tolerating R935788 and the cancer is either stable or getting better. - Researchers will conduct the following additional tests to see how the study is affecting the patient: - Other research blood samples will be collected before treatment, at cycle 1 week 3, at the beginning of cycle 2, and at 8 weeks. - Optional tumor biopsies will be requested before starting treatment, at cycle 1 day 28. - Patients with specific lesions or tumors may be asked for an optional tumor biopsy on day 8.
NCT01167868 ↗	A Study to Assess the Safety, Tolerability, and Blood and Urine Drug Levels of Fostamatinib Disodium (FosD) in Healthy Japanese and White Subjects	Completed	AstraZeneca	Phase 1	2010-07-01	This is a single and multiple ascending dose study in healthy male and female (of non-child bearing potential) Japanese and White volunteers, to assess the safety, tolerability, and blood and urine drug levels of FosD. FosD is being developed for the treatment of rheumatoid arthritis.
NCT01197521 ↗	Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Not Responding.	Completed	AstraZeneca	Phase 3	2010-09-01	The purpose of the study is to evaluate the effectiveness of two dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking methotrexate but not responding. The study will last for 1 year.
NCT01197534 ↗	Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Disease Modifying Anti-rheumatic Drug (DMARD) But Not Responding.	Completed	AstraZeneca	Phase 3	2010-09-01	The purpose of the study is to evaluate the effectiveness of two dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking disease modifying anti-rheumatic drug (DMARD) but not responding. The study will last for 1 year.

Clinical Trial Conditions for Fostamatinib Disodium

Condition Name

Condition Name for Fostamatinib Disodium
Intervention	Trials
Rheumatoid Arthritis	6
Immune Thrombocytopenic Purpura	3
Warm Antibody Autoimmune Hemolytic Anemia	3
Healthy Volunteers	2

Condition MeSH

Condition MeSH for Fostamatinib Disodium
Intervention	Trials
Arthritis, Rheumatoid	6
Arthritis	6
Purpura, Thrombocytopenic, Idiopathic	4
Purpura, Thrombocytopenic	4

Clinical Trial Locations for Fostamatinib Disodium

Trials by Country

Trials by Country for Fostamatinib Disodium
Location	Trials
United States	222
United Kingdom	31
Canada	24
Brazil	21
Australia	19

Trials by US State

Trials by US State for Fostamatinib Disodium
Location	Trials
New York	13
California	12
Arizona	10
Maryland	10
Texas	10

Clinical Trial Progress for Fostamatinib Disodium

Clinical Trial Phase

Clinical Trial Phase for Fostamatinib Disodium
Clinical Trial Phase	Trials
Phase 3	10
Phase 2	6
Phase 1	3

Clinical Trial Status

Clinical Trial Status for Fostamatinib Disodium
Clinical Trial Phase	Trials
Completed	13
Terminated	3
Recruiting	2

Clinical Trial Sponsors for Fostamatinib Disodium

Sponsor Name

Sponsor Name for Fostamatinib Disodium
Sponsor	Trials
AstraZeneca	9
Rigel Pharmaceuticals	9
National Cancer Institute (NCI)	1

Sponsor Type

Sponsor Type for Fostamatinib Disodium
Sponsor	Trials
Industry	18
NIH	1

FOSTAMATINIB DISODIUM: Clinical Trials Update, Market Analysis, and Projections

Introduction

Fostamatinib disodium, marketed as Tavalisse, is a spleen tyrosine kinase (Syk) inhibitor that has been approved by the FDA for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to previous treatments. Here, we will delve into the recent clinical trials, market analysis, and future projections for this drug.

Clinical Trials Update

Chronic Immune Thrombocytopenia (ITP)

Fostamatinib has been extensively studied in several Phase 3 clinical trials for the treatment of ITP. The FIT1 and FIT2 trials, conducted in North America, Australia, and Europe, demonstrated significant efficacy. In these trials, 43% of patients receiving fostamatinib achieved an overall response, defined as a platelet count greater than 50 × 10^9/L within the first 12 weeks, compared to 14% in the placebo arm[2].

In Japan, a Phase 3 trial also showed promising results, with patients receiving fostamatinib achieving a stable platelet response significantly higher than those on placebo. The safety profile was consistent with previous trials, with no new or unusual safety issues observed[1].

Warm Autoimmune Hemolytic Anemia (wAIHA)

The FORWARD Phase 3 clinical trial evaluated fostamatinib in patients with wAIHA who had failed at least one prior treatment. Although the trial did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the overall study population, a post-hoc regional analysis showed favorable outcomes in patients from the U.S., Canada, Australia, and Western Europe. However, patients from Eastern European sites did not show the same benefit[4].

COVID-19

Fostamatinib has also been investigated in the context of COVID-19. A Phase 2 trial sponsored by the NIH/NHLBI showed that fostamatinib, when added to standard care, was well-tolerated and associated with improved clinical outcomes in hospitalized patients. The study indicated reduced severity of adverse events and improved metrics such as time to sustained recovery and days on oxygen[3].

Mechanism of Action and Safety Profile

Fostamatinib is a prodrug that is converted to its active metabolite, R406, which inhibits Syk. This inhibition affects platelet activation and immune responses, making it effective for conditions like ITP and potentially wAIHA. The drug has a terminal half-life of approximately 15 hours and is rapidly absorbed into circulation[2].

The safety profile of fostamatinib includes common adverse reactions such as diarrhea, hypertension, nausea, and increased liver enzymes. Serious adverse reactions, though rare, include febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis. Monthly monitoring of liver function tests and absolute neutrophil count is recommended[5].

Market Analysis

Current Market Position

Fostamatinib was approved by the FDA in April 2018 for the treatment of ITP, marking a significant milestone for patients who had limited treatment options. The drug has since been integrated into clinical guidelines as a second-line or third-line treatment for ITP, offering an alternative to traditional therapies like corticosteroids, immunoglobulins, and thrombopoietin receptor agonists[5].

Market Size and Growth

The market for ITP treatments is growing due to the increasing prevalence of the condition and the need for effective therapies. Fostamatinib's approval has captured a significant share of this market, particularly among patients who have failed previous treatments. The global ITP treatment market is projected to grow, driven by the increasing incidence of autoimmune diseases and the expanding use of targeted therapies like fostamatinib.

Competitive Landscape

The ITP treatment market is competitive, with other therapies such as romiplostim and eltrombopag also available. However, fostamatinib's unique mechanism of action and its approval for patients with insufficient response to previous treatments position it as a valuable option in the treatment arsenal. The potential expansion of its indications to other autoimmune conditions, such as wAIHA, could further enhance its market presence.

Future Projections

Expanding Indications

The ongoing and planned clinical trials for fostamatinib in conditions like wAIHA and COVID-19 could significantly expand its market potential. Positive outcomes in these trials could lead to additional FDA approvals, increasing the drug's reach and revenue.

Geographical Expansion

The drug's performance in different geographical regions, as seen in the FORWARD trial, highlights the need for regional analyses. Successful outcomes in specific regions could lead to targeted marketing and distribution strategies, further boosting sales.

Patient Population and Unmet Needs

Fostamatinib addresses a significant unmet need in the treatment of chronic ITP and potentially other autoimmune conditions. As awareness and diagnosis rates improve, the demand for effective treatments like fostamatinib is likely to increase.

Key Takeaways

• Clinical Efficacy: Fostamatinib has demonstrated significant efficacy in treating chronic ITP and shows promise in other autoimmune conditions like wAIHA and COVID-19.
• Safety Profile: The drug has a manageable safety profile, with common adverse reactions and rare but serious side effects.
• Market Position: Fostamatinib is a key player in the ITP treatment market and has the potential to expand into other autoimmune conditions.
• Future Growth: The drug's market is expected to grow with expanding indications, geographical expansion, and increasing awareness of autoimmune diseases.

FAQs

What is fostamatinib disodium used for?

Fostamatinib disodium is primarily used for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to previous treatments.

What are the common side effects of fostamatinib?

Common side effects include diarrhea, hypertension, nausea, increased liver enzymes, and respiratory infections. Serious side effects are rare but can include febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis.

Is fostamatinib effective for conditions other than ITP?

Fostamatinib is being studied for other conditions such as warm autoimmune hemolytic anemia (wAIHA) and COVID-19, with promising results in some trials.

How does fostamatinib work?

Fostamatinib is a spleen tyrosine kinase (Syk) inhibitor that affects platelet activation and immune responses, making it effective for autoimmune conditions like ITP.

What is the recommended dosage of fostamatinib?

The recommended initial dose is 100 mg administered orally twice daily, which can be increased to 150 mg twice daily after one month if the platelet count has not increased to at least 50 × 10^9/L[5].

Is fostamatinib approved for use in children?

No, fostamatinib is currently approved only for the treatment of adult patients with chronic ITP.

Sources

1. Rigel Pharmaceuticals: "Fostamatinib Meets Primary Endpoint in Phase 3 Trial in Japan for Treatment of Chronic Immune Thrombocytopenia"[1]
2. Blood: "Fostamatinib for the treatment of chronic immune thrombocytopenia"[2]
3. Rigel Pharmaceuticals: "Data from NIH/NHLBI-Sponsored Phase 2 Trial of Fostamatinib in Hospitalized COVID-19 Patients Published in Clinical Infectious Diseases"[3]
4. Rigel Pharmaceuticals: "Rigel Announces Top-line Results from FORWARD Phase 3 Clinical Trial of Fostamatinib in Patients with Warm Autoimmune Hemolytic Anemia"[4]
5. FDA: "FDA approves fostamatinib tablets for ITP"[5]