Rigel's Fostamatinib Being Studied by National Institute of Health in Patients with Sickle Cell Disease
Rigel Pharmaceuticals (NASDAQ: RIGL) announced the enrollment of the first patient in a NIH/NHLBI-sponsored Phase 1 study evaluating fostamatinib in sickle cell disease (SCD) patients. The study will assess the safety and tolerability of escalating doses of fostamatinib, Rigel's oral SYK inhibitor, which is already approved as TAVALISSE® for chronic immune thrombocytopenia.
The open-label Phase 1 dose-escalation study aims to enroll approximately 20 patients with SCD. Patients will receive 100 mg twice daily for 14 days, potentially escalating to 150 mg twice daily for an additional 28 days if tolerated. The study will evaluate safety, tolerability, and investigate fostamatinib's mechanism of action in SCD, including its effects on red blood cell membrane integrity, sickling kinetics, and platelet activation.
The trial is being conducted at the NIH Clinical Center in Bethesda, Maryland, with study material provided by Rigel. SCD affects over 100,000 people in the United States and an estimated 7-8 million people worldwide.
Rigel Pharmaceuticals (NASDAQ: RIGL) ha annunciato l'arruolamento del primo paziente in uno studio di Fase 1 sponsorizzato dal NIH/NHLBI che valuta il fostamatinib nei pazienti affetti da malattia delle cellule falciformi (SCD). Lo studio valuterà la sicurezza e la tollerabilità di dosi crescenti di fostamatinib, un inibitore orale della SYK di Rigel, già approvato come TAVALISSE® per la trombocitopenia immune cronica.
Lo studio di Fase 1 a dose crescente si propone di arruolare circa 20 pazienti con SCD. I pazienti riceveranno 100 mg due volte al giorno per 14 giorni, con la possibilità di aumentare a 150 mg due volte al giorno per ulteriori 28 giorni, se tollerato. Lo studio valuterà sicurezza, tollerabilità e indagherà il meccanismo d'azione del fostamatinib nella SCD, inclusi i suoi effetti sull'integrità della membrana dei globuli rossi, sulla cinetica di falcizzazione e sull'attivazione delle piastrine.
Il trial si svolge presso il NIH Clinical Center di Bethesda, Maryland, con materiale di studio fornito da Rigel. La SCD colpisce oltre 100.000 persone negli Stati Uniti e si stima che riguardi 7-8 milioni di persone in tutto il mondo.
Rigel Pharmaceuticals (NASDAQ: RIGL) anunció la inscripción del primer paciente en un estudio de Fase 1 patrocinado por el NIH/NHLBI que evalúa el fostamatinib en pacientes con enfermedad de células falciformes (SCD). El estudio evaluará la seguridad y tolerabilidad de dosis crecientes de fostamatinib, un inhibidor oral de SYK de Rigel, que ya está aprobado como TAVALISSE® para la trombocitopenia inmune crónica.
El estudio de Fase 1 a dosis en escalada tiene como objetivo inscribir aproximadamente 20 pacientes con SCD. Los pacientes recibirán 100 mg dos veces al día durante 14 días, con la posibilidad de aumentar a 150 mg dos veces al día durante otros 28 días, si son tolerados. El estudio evaluará la seguridad, la tolerabilidad e investigará el mecanismo de acción del fostamatinib en la SCD, incluyendo sus efectos en la integridad de la membrana de los glóbulos rojos, la cinética de la falcificación y la activación de las plaquetas.
El ensayo se realiza en el NIH Clinical Center en Bethesda, Maryland, con material de estudio proporcionado por Rigel. La SCD afecta a más de 100,000 personas en los Estados Unidos y se estima que hay entre 7 y 8 millones de personas en todo el mundo afectadas.
리겔 제약 (NASDAQ: RIGL)은 NIH/NHLBI가 후원하는 1상 연구에 첫 번째 환자가 등록되었음을 발표했습니다. 이 연구는 겸상 적혈구 질환(SCD) 환자에 대한 포스타마티닙 평가를 목적으로 하고 있습니다. 연구는 리겔의 경구 SYK 억제제인 포스타마티닙의 안전성과 내약성을 평가할 것입니다. 포스타마티닙은 만성 면역성 혈소판감소증에 대해 TAVALISSE®로 이미 승인되었습니다.
이 공개 라벨 1상 용량 상승 연구는 대략 20명의 환자를 등록하는 것을 목표로 하고 있습니다. 환자들은 14일 동안 하루 두 번 100mg을 복용하고, 내약성이 있을 경우 추가 28일 동안 하루 두 번 150mg으로 증량될 수 있습니다. 연구는 안전성, 내약성을 평가하고 겸상 적혈구 질환에서 포스타마티닙의 작용 메커니즘을 조사할 것이며, 적혈구막의 무결성, 겸상 발생 동역학, 혈소판 활성화에 대한 영향을 포함할 것입니다.
시험은 메릴랜드주 베세스다에 있는 NIH 임상 센터에서 진행되며, 연구 자료는 리겔에서 제공합니다. SCD는 미국에서 100,000명 이상의 사람들에게 영향을 미치며, 전 세계적으로 700만에서 800만 명이 영향을 받고 있는 것으로 추정됩니다.
Rigel Pharmaceuticals (NASDAQ: RIGL) a annoncé l'inscriptions du premier patient dans une étude de phase 1 parrainée par le NIH/NHLBI, évaluant le fostamatinib chez des patients atteints de drépanocytose (SCD). L'étude évaluera la sécurité et la tolérabilité de doses croissantes de fostamatinib, un inhibiteur oral de SYK de Rigel, déjà approuvé comme TAVALISSE® pour la thrombocytopénie immunitaire chronique.
L'étude ouverte de phase 1 vise à recruter environ 20 patients atteints de SCD. Les patients recevront 100 mg deux fois par jour pendant 14 jours, avec la possibilité d'augmenter à 150 mg deux fois par jour pendant 28 jours supplémentaires si cela est bien toléré. L'étude évaluera la sécurité, la tolérabilité et investiguera le mécanisme d'action du fostamatinib dans la SCD, y compris ses effets sur l'intégrité de la membrane des globules rouges, la cinétique de la déformation en faucille et l'activation des plaquettes.
L'essai est mené au NIH Clinical Center à Bethesda, Maryland, avec le matériel d'étude fourni par Rigel. La SCD affecte plus de 100 000 personnes aux États-Unis et environ 7 à 8 millions de personnes dans le monde.
Rigel Pharmaceuticals (NASDAQ: RIGL) hat die Aufnahme des ersten Patienten in eine von NIH/NHLBI unterstützte Phase 1-Studie zur Bewertung von Fostamatinib bei Patienten mit Sichelzellenerkrankung (SCD) bekannt gegeben. Die Studie wird die Sicherheit und Verträglichkeit von steigenden Dosen von Fostamatinib, einem oralen SYK-Inhibitor von Rigel, untersuchen, der bereits als TAVALISSE® für chronische immunbedingte Thrombozytopenie zugelassen ist.
Die offene Phase 1-Dosiserhöhungstudie zielt darauf ab, etwa 20 Patienten mit SCD zu rekrutieren. Die Patienten erhalten 100 mg zweimal täglich über 14 Tage, eventuell steigend auf 150 mg zweimal täglich für weitere 28 Tage, sofern gut verträglich. Die Studie wird die Sicherheit, Verträglichkeit und den Mechanismus des Wirkens von Fostamatinib bei SCD bewerten, einschließlich seiner Auswirkungen auf die Integrität der roten Blutkörperchen, die Sichelbildung und die Aktivierung der Thrombozyten.
Die Studie wird im NIH Clinical Center in Bethesda, Maryland, durchgeführt, wobei das Studienmaterial von Rigel bereitgestellt wird. SCD betrifft über 100.000 Menschen in den Vereinigten Staaten und schätzungsweise 7-8 Millionen Menschen weltweit.
- NIH/NHLBI sponsorship adds credibility and reduces research costs for Rigel
- Potential expansion of fostamatinib into new indication (SCD) with large market potential
- Study explores new mechanism of action that could address unmet needs in SCD treatment
- Early-stage Phase 1 study with small patient population (20 patients)
- Long development timeline before potential commercialization
- Multiple safety concerns highlighted in TAVALISSE's current indication
Insights
The initiation of an NIH-sponsored Phase 1 trial for fostamatinib in sickle cell disease (SCD) represents a significant opportunity for Rigel Pharmaceuticals. Here's why this matters: Fostamatinib is already FDA-approved as TAVALISSE® for chronic immune thrombocytopenia, which means its safety profile is well-established, potentially streamlining the development process for this new indication.
The market implications are substantial - SCD affects over 100,000 people in the U.S. and approximately 7-8 million worldwide. Current treatment options are and the condition imposes a significant burden on healthcare systems. The NIH's involvement provides credibility and financial support, effectively de-risking the development process for Rigel.
In simpler terms: Think of sickle cell disease as a condition where blood cells become rigid and crescent-shaped, causing painful blockages in blood vessels. Fostamatinib works by targeting a specific enzyme (SYK) that contributes to this problem. If successful, it could help keep blood cells healthier and prevent these painful episodes.
The trial's design is particularly interesting as it focuses on multiple aspects of the disease, including red blood cell membrane stability and inflammation markers. This comprehensive approach could potentially position fostamatinib as a unique treatment option in the SCD market.
First patient enrolled in NIH/NHLBI-sponsored Phase 1 Study of fostamatinib, Rigel's oral SYK inhibitor
"Our Phase 1 study evaluating fostamatinib in patients with sickle cell disease is an opportunity to explore a potential new treatment option for a disease that is associated with a high degree of recurrent acute pain events and other acute and chronic potentially life-threatening complications," stated Richard Childs, M.D., scientific director of the NHLBI. "Preclinical research conducted by NIH/NHLBI investigators lead us to believe that SYK inhibition may have the potential to reduce complications related to red cell sickling and thrombo-inflammation in this patient population."
"We are excited to support another important study conducted by the NIH/NHLBI for fostamatinib, as they investigate SYK inhibition and its potential to benefit patients with sickle cell disease, a devasting, lifelong condition," said Raul Rodriguez, Rigel's president and CEO. "The study focuses on an area of critical unmet need and contributes to Rigel's mission to improve the lives of patients with hematologic disorders and cancer."
This open label Phase 1 dose-escalation study is expected to enroll approximately 20 patients with SCD (NCT05904093). The trial is led by principal investigator Swee Lay Thein, M.D., senior investigator and chief of the Sickle Cell Branch at the NHLBI. Patients will receive oral fostamatinib at a dose of 100 mg twice daily for 14 days, which will be escalated to 150 mg twice daily for an additional 28 days if tolerated. The primary objective of the study is to evaluate the safety and tolerability of fostamatinib. The secondary and exploratory objectives are to assess the mechanism of action of fostamatinib in SCD and mechanistic effects of fostamatinib mediated SYK inhibition on red blood cell membrane integrity and deformability, rate of sickling kinetics, platelet activation and aggregation, and neutrophil activation and neutrophil extracellular trap (NET) formation. The clinical study is being conducted at the NIH Clinical Center in
About SCD & SYK Inhibition
Sickle cell disease (SCD) is a genetic hemoglobinopathy that leads to the production of abnormal hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become rigid and crescent – or "sickle" – shaped, leading to strokes, infections, vaso-occlusive crises (VOC), and multi-organ dysfunction. The condition affects more than 100,000 people in
In preclinical studies, R406, the active metabolite of fostamatinib, was shown to inhibit production of neutrophil extracellular traps (NETs) by neutrophils in vitro.3 In a humanized SCD mouse model, R406 treatment significantly decreased platelet ATP secretion and aggregation in response to collagen without a significant effect on bleeding time.4 Fostamatinib could potentially ameliorate SCD-related prothrombic state without an increase in bleeding, addressing an important unmet need. Furthermore, tyrosine phosphorylation of red blood cell (RBC) Band 3 (the anion exchanger 1, of the SLC4A1 gene) compromises the RBC's integrity, leading to shedding of red cell derived microparticles and release of hemoglobin and mitochondrial DNA, key contributors to thrombo-inflammation pathophysiology. By impacting phosphorylation of RBC Band 3 protein, fostamatinib offers the potential for enhanced RBC membrane stability and reduced sickling of RBCs.5
About TAVALISSE®
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Important Safety Information
Warnings and Precautions
- Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
- Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
- Diarrhea occurred in
31% of patients and severe diarrhea occurred in1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. - Neutropenia occurred in
6% of patients treated with TAVALISSE; febrile neutropenia occurred in1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. - TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions
- Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
- It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
- Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
- Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions
- Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in
1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both2% ), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all1% ). - Common adverse reactions (≥
5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSEUSPI.com for Full Prescribing Information.
To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).
TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc.
Disclaimer
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Rigel
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in
- National Heart, Lung, and Blood Institute. Sickle Cell Disease | What Is Sickle Cell Disease? Accessed January 3, 2025. https://www.nhlbi.nih.gov/health/sickle-cell-disease
- G. B. D. S. C. D. Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Aug;10(8):e585-e599. doi: 10.1016/S2352-3026(23)00118-7. Epub 2023 Jun 15.
- Strich JR, Ramos-Benitez MJ, Randazzo D, Stein SR, Babyak A, Davey RT, Suffredini AF, Childs RW, Chertow DS. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic. J Infect Dis. 2021 Mar 29;223(6):981-984.
- Vogel S, Kamimura S, Smith ML, et al. SYK inhibition suppresses NLRP3 inflammasome activation in platelets from sickle cell mice leading to decreased platelet secretion, aggregation, spreading, and in vitro thrombus formation. Thromb Res. 2024;237:18-22
- Noomuna P, Risinger M, Zhou S, et al. Inhibition of Band 3 tyrosine phosphorylation: a new mechanism for treatment of sickle cell disease. Br J Haematol. 2020;190(4):599-609.
Forward Looking Statements
This press release contains forward-looking statements relating to, among other things, evaluating fostamatinib in patients with sickle cell disease and the potential of SYK inhibition to reduce complications related to red cell sickling and thrombo-inflammation. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "explore", "potential", "may", "expected", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the development and commercialization of fostamatinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law.
Contact for Investors & Media:
Investors:
Rigel Pharmaceuticals, Inc.
650.624.1232
ir@rigel.com
Media:
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646.461.6387
david.rosen@argotpartners.com
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FAQ
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