What Is Fostamatinib?
Fostamatinib is an FDA-approved medication for chronic idiopathic thrombocytopenia purpura (ITP). It functions as a Syk kinase inhibitor. Syk (spleen tyrosine kinase) is an enzyme found inside immune cells that is involved in signaling pathways. By blocking the activity of Syk, fostamatinib helps to regulate immune responses, which can be beneficial in conditions where the immune system is overactive or mistakenly attacks the body's own cells.
In addition to its approved use, fostamatinib is under investigation for a range of other conditions. These include various immune-mediated disorders such as rheumatoid arthritis, warm antibody autoimmune hemolytic anemia, immune mediated anemia, and chronic graft-versus-host disease (GVHD). Researchers are also exploring its potential in certain cancers, including pancreatic ductal adenocarcinoma and ovarian cancer, as well as in viral infections like COVID-19. The drug has been studied in a total of 62 trials involving over 10,000 participants since the first trial began in 2007.
Uses and Conditions Under Study
Fostamatinib has been studied in a wide range of conditions, reflecting its role as a Syk kinase inhibitor that modulates immune responses. A total of 62 trials have been conducted with 10,078 participants since 2007.
Many studies focus on immune and blood disorders. For example, it is FDA-approved for Immune Thrombocytopenic Purpura (ITP), a condition where the immune system attacks platelets, leading to bleeding. Fostamatinib is also being investigated for warm antibody autoimmune hemolytic anemia (3 trials) and immune mediated anemia (2 trials), both conditions involving the immune system attacking red blood cells. Chronic graft-versus-host disease (2 trials), a complication after stem cell transplant where donor immune cells attack recipient tissues, is another area of study.
Inflammatory and autoimmune conditions are also a significant focus. Rheumatoid Arthritis, an autoimmune disease causing joint inflammation, has been studied in 18 trials. IGA Nephropathy (2 trials), a kidney disease caused by immune deposits, is also under investigation.
Fostamatinib has been explored for its potential in certain infections, specifically Coronavirus Infection (2 trials) and COVID-19 (2 trials). The drug's ability to modulate immune responses might help manage the severe inflammation seen in these viral illnesses.
In oncology, fostamatinib is being studied for its use in certain cancers. This includes pancreatic ductal adenocarcinoma, where it is hypothesized to reprogram macrophages to an immunostimulatory phenotype in the tumor microenvironment. It has also been evaluated in recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.
Additionally, some trials have focused on understanding the drug's properties, such as pharmacokinetics (4 trials) in healthy volunteers (4 trials) and in participants with Sickle Cell Disease, to understand how the body processes the medication.
Dosing
Fostamatinib is primarily administered orally, typically as tablets. Strengths studied in clinical trials include 50 mg, 100 mg, and 150 mg tablets. Some studies also mention a 200 mg dose.
Investigational dosing regimens often involve starting with a lower dose and escalating based on tolerability and response. For example, some studies initiated fostamatinib at 100 mg once daily for 14 days, then escalated to 100 mg twice daily (BID) for 14 days, and further to 150 mg twice daily for 28 days. Another regimen involved 100 mg twice daily for 14 days, escalating to 150 mg twice daily for 28 days if tolerated.
Dose escalation cohorts have been used to identify optimal and maximally tolerated doses, particularly when fostamatinib is combined with other treatments, such as chemotherapy agents like paclitaxel, gemcitabine, and nab-paclitaxel. In some extended access studies, patients received fostamatinib at the same dose as their previous study, with options for dose reduction (e.g., to 100 mg daily, 150 mg daily, or 100 mg twice daily) if dose-limiting adverse events occurred.
Fostamatinib has been studied both as a standalone treatment and in combination with standard of care therapies or other investigational drugs like ruxolitinib.
Side Effects
In clinical trials, the most common side effect reported by patients taking Fostamatinib was hypertension. Across 7 trials involving 2,141 patients, 16.6% of patients on Fostamatinib experienced hypertension, compared to 5.2% of patients on placebo. Diarrhea was also frequently reported, affecting 14.4% of patients on Fostamatinib (across 15 trials with 3,085 patients), versus 4.4% on placebo.
Other common side effects observed in patients taking Fostamatinib included:
- Nasopharyngitis (common cold symptoms): 7.9% of patients on Fostamatinib experienced this, compared to 2.8% on placebo (6 trials, 1,837 patients).
- Nausea: 6.3% of patients on Fostamatinib experienced nausea, compared to 1.8% on placebo (6 trials, 862 patients).
- Increased Alanine Aminotransferase (ALT), a liver enzyme: 5.5% of patients on Fostamatinib had increased ALT levels, compared to 1.6% on placebo (5 trials, 1,624 patients).
- Headache: 5.5% of patients on Fostamatinib experienced headaches, compared to 3.5% on placebo (6 trials, 1,928 patients).
- Increased blood pressure: 5.2% of patients on Fostamatinib had increased blood pressure, compared to 1.7% on placebo (2 trials, 1,220 patients).
- Increased Aspartate Aminotransferase (AST), another liver enzyme: 4.8% of patients on Fostamatinib had increased AST levels, compared to 1.3% on placebo (3 trials, 1,281 patients).
Clinical Trial Results
Fostamatinib has been studied in various clinical trials for different conditions:
B-cell Lymphoma
In an efficacy and safety study (NCT00446095) for B-cell lymphoma, Fostamatinib (also known as R788) showed the following results:
- Clinical Benefit Rate (defined as complete response, partial response, or stable disease): All 9 participants in Phase 1 (200mg and 250mg R788 BID), all 13 participants in Phase II (250mg R788 BID), all 9 participants with Diffuse Large B-cell Lymphoma (DLBCL), and all 14 participants with other lymphomas achieved clinical benefit.
- Overall Response Rate (defined as complete or partial response): 1 participant in Phase 1 (200mg and 250mg R788 BID), 2 participants in Phase II (250mg R788 BID), 5 participants with DLBCL, and 7 participants with other lymphomas achieved an overall response.
- Median Overall Survival for patients with DLBCL was 166.0 days.
- Median Progression-Free Survival was 141.0 days for patients on 250mg R788 BID, 83.0 days for patients with DLBCL, and 126.0 days for patients with other lymphomas.
Rheumatoid Arthritis
Two studies evaluated Fostamatinib (R788) for rheumatoid arthritis:
In the Taski-3 study (NCT00665626), at 3 months, 56 participants taking Fostamatinib 100 mg twice daily achieved an ACR20 response (a 20% improvement in rheumatoid arthritis symptoms), compared to 27 participants on placebo. Imaging scores also showed improvement: the mean Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Osteitis Score decreased by 0.19 in the Fostamatinib group, while it increased by 0.94 in the placebo group. Similarly, the RAMRIS Synovitis Score decreased by 0.52 with Fostamatinib, compared to an increase of 0.35 with placebo.
Another study (NCT00665925) showed that at 6 months:
- ACR20 response was achieved by 87 participants on Fostamatinib 150 mg once daily and 101 participants on Fostamatinib 100 mg twice daily, compared to 53 participants on pooled placebo.
- ACR50 response was achieved by 49 participants on Fostamatinib 150 mg once daily and 65 participants on Fostamatinib 100 mg twice daily, compared to 29 participants on pooled placebo.
- ACR70 response was achieved by 21 participants on Fostamatinib 150 mg once daily and 43 participants on Fostamatinib 100 mg twice daily, compared to 16 participants on pooled placebo.
- Patients on Fostamatinib 100 mg twice daily also reported a mean improvement of 7.4 in their Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at 6 months, indicating reduced fatigue, compared to a 4.5 improvement with pooled placebo.
Immune Thrombocytopenic Purpura (ITP)
A pilot study (NCT00706342) for adult refractory ITP found that Fostamatinib (R788) led to an increase in platelet count (at least 20,000/mm3 from baseline to a total of 30,000/mm3 or more) in:
- 8 participants by Week 2.
- 5 participants by Week 12.
- 5 participants by Month 12.
T-Cell Lymphoma
In an efficacy and safety study (NCT00798096) for T-cell lymphoma, 5 participants achieved a clinical benefit rate. However, 0 participants achieved an overall response rate. An overall regressive response rate (defined as complete response, partial response, or regressive stable disease) was observed in 4 participants.
Currently Recruiting Trials
Fostamatinib is currently being investigated in several clinical trials, exploring its potential across a range of conditions. These studies aim to gather more information about its safety and effectiveness, offering opportunities for patients to contribute to medical research. One ongoing Phase 1 study, NCT06233110, is evaluating fostamatinib in combination with ruxolitinib for chronic Graft Versus Host Disease (cGvHD) that has not responded well to corticosteroids. This open-label study, sponsored by Stefanie Sarantopoulos, MD, PhD., plans to enroll 30 participants to identify a safe and effective dose of fostamatinib when added to standard care. Researchers are testing several dose escalation levels to find the optimal combination. Another Phase 1 study, NCT05904093, sponsored by the National Heart, Lung, and Blood Institute (NHLBI), is investigating fostamatinib for individuals with stable Sickle Cell Disease. This trial aims to assess the safety and tolerability of escalating doses of fostamatinib in 25 participants. The study seeks to understand how the drug is handled by the body in people with this genetic blood disorder. For patients with resectable pancreatic cancer, a Phase 1b trial, NCT06639724, is recruiting 36 participants. Sponsored by the University of California, San Diego, this study combines fostamatinib with standard chemotherapy agents, gemcitabine and nab-paclitaxel, to evaluate its use in the perioperative treatment of Pancreatic Ductal Adenocarcinoma (PDAC). A special drug use-results survey, NCT06757257, is underway for Japanese patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP). This survey, sponsored by Kissei Pharmaceutical Co., Ltd., aims to evaluate the long-term safety and efficacy of fostamatinib under real-world conditions, involving 149 participants. Finally, an open-label Phase 3 extension study, NCT04138927, sponsored by Rigel Pharmaceuticals, is focused on the long-term safety of fostamatinib for individuals with Warm Antibody Autoimmune Hemolytic Anemia (wAIHA). This study is enrolling 90 participants to gather extensive safety data over an extended period.Where to Participate
Clinical trials for fostamatinib are conducted across various locations, providing opportunities for participation in different regions. The research has a broad geographic reach, with active sites in several states. The top locations currently recruiting participants include:- La Jolla, California
- Los Angeles, California
- Torrance, California
- Washington D.C., District of Columbia
- Baltimore, Maryland
- Bethesda, Maryland
- Boston, Massachusetts
- Las Vegas, Nevada
- Durham, North Carolina
- Olympia, Washington