RegulationFast Track (United States), Orphan Drug (United States), Orphan Drug (European Union), Priority Review (China), Orphan Drug (South Korea), Paediatric investigation plan (European Union), Conditional marketing approval (China), Orphan Drug (Japan)

Structure/Sequence

Sequence Code 37465

Source: *****

Clinical Trials associated with Luspatercept-AAMT

NCT07096297

/ Not yet recruitingPhase 2IIT

A Phase II Study of Luspatercept Plus Darbepoetin Alfa in Non-mutated SF3B1 Lower-risk Myelodysplastic Syndromes

This is a single arm open-label Phase II trial of luspatercept and darbepoetin alfa in non-mutated SF3B1 , lower-risk, RBC transfusion dependent MDS participants with an endogenous erythropoietin (EPO) level < 500 IU/L.

Start Date01 Dec 2025

Sponsor / Collaborator

Yale University

[+1]

ChiCTR2500111793

/ Not yet recruitingPhase 2IIT

Luspatercept for Refractory Poor Platelet Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center, Single-Arm, Prospective Clinical Study

Start Date01 Nov 2025

Sponsor / Collaborator

Zhejiang Chinese Medicine Hospital

[+1]

NCT07215975

/ Not yet recruitingNot Applicable

REal-World Application of Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East (RELATE): A Non-interventional Retrospective and Prospective Observational Study

The purpose of this study is to evaluate luspatercept treatment in adults with transfusion-dependent beta-Thalassemia in the Middle East

Start Date25 Oct 2025

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with Luspatercept-AAMT

100 Translational Medicine associated with Luspatercept-AAMT

100 Patents (Medical) associated with Luspatercept-AAMT

258

Literatures (Medical) associated with Luspatercept-AAMT

31 Dec 2025·JOURNAL OF MEDICAL ECONOMICS

Healthcare resource utilization of patients with lower-risk myelodysplastic syndromes treated with luspatercept versus erythropoiesis-stimulating agents: a United States healthcare claims database study

Article

Author: Mohan, Manasi ; Yenikomshian, Mihran ; Huynh, Lynn ; Swanson, Ashley ; Pinaire, Megan ; Tang, Derek ; Slaff, Samantha ; Zanardo, Enrico ; Song, Rui ; Gavrilov, Svetlana ; Ball, Brian J.

OBJECTIVE:

This study compared the healthcare resource utilization (HRU) of patients with lower-risk myelodysplastic syndromes (LR-MDS) treated with luspatercept versus erythropoiesis-stimulating agents (ESAs).

METHODS:

This real-world retrospective cohort study used claims data from the Symphony Health Integrated Dataverse, a large nationally representative United States database, to identify patients with LR-MDS who initiated luspatercept or ESA between May 1, 2020, and June 30, 2022. Index date was defined as the date of the first claim for luspatercept or ESA. The follow-up period was from the index date to the earliest of the end of clinical activity or end of data availability. All-cause and MDS-related HRU were evaluated for both treatment cohorts and compared using generalized estimating equations with Poisson distribution and robust variance estimator.

RESULTS:

Overall, 243 and 3,515 patients were included in the luspatercept and ESA cohorts, respectively. Patients in both cohorts had a similar median (interquartile range [IQR]) age at index (luspatercept: 77.0 [70.0-79.0] years; ESA: 78.0 [72.0-79.0] years) and median (IQR) follow-up duration (luspatercept: 14.6 [10.4-22.6] months; ESA: 14.4 [9.5-20.9] months). Compared with patients treated with ESA, patients treated with luspatercept had a 26% lower rate of all-cause inpatient visits (adjusted incidence rate ratio [aIRR], 0.74; 95% confidence interval [CI], 0.58-0.93; p < .05) and a 31% lower rate of all-cause outpatient visits (aIRR, 0.69; 95% CI, 0.61-0.79; p < .001). The rate of MDS-related inpatient visits was also 25% lower among the patients treated with luspatercept versus ESA (aIRR, 0.75; 95% CI, 0.56-0.99; p < .05).

CONCLUSION:

This study showed that patients with LR-MDS treated with luspatercept required significantly less HRU than patients treated with ESA. Further research is warranted to evaluate the financial impact of this lower HRU burden.

31 Dec 2025·JOURNAL OF MEDICAL ECONOMICS

Treatment patterns and outcomes in patients with lower-risk myelodysplastic syndromes treated with erythropoiesis-stimulating agents in a large US community oncology practice: a retrospective chart review

Article

Author: Gavrilov, Svetlana ; Gordan, Lucio N. ; Ming, Amy ; Alajrash, Aya ; Swanson, Ashley ; Griffin, Ernest ; Warner, Amanda ; Slaff, Samantha ; Heritage, Trevor ; Tang, Derek ; Singh, Nisha ; Fonseca, Gustavo

BACKGROUND:

Erythropoiesis-stimulating agents (ESAs) are an established treatment for lower-risk myelodysplastic syndromes (LR-MDS). However, real-world data on the outcomes of patients with LR-MDS treated with ESAs are limited. This study describes treatment patterns and clinical outcomes in this population.

METHODS:

This is a retrospective review of electronic medical records compiled from Florida Cancer Specialists & Research Institute databases. Inclusion criteria were: LR-MDS diagnosis (between January 2018 through December 2022), initiation of ESA treatment, ≥18 years at diagnosis, availability of ≥6 months of data prior to diagnosis, and ≥1 year of follow-up data. Patients treated with luspatercept prior to ESAs or enrolled in clinical trials during the study period were excluded. Patients were followed for 1 year from the initial diagnosis until loss to follow-up/death. Outcomes included treatment patterns (occurrence of and time to ESA failure, and time on ESA treatment after failure), and clinical outcomes related to ESA failure (hematologic improvement and transfusion independence), with ESA failure defined as a < 1.5 g/dL rise in hemoglobin or no decrease in red blood cell transfusions by 6-8 weeks of treatment.

RESULTS:

At baseline, of 359 eligible patients with LR-MDS most were male (65.2%), White (88.0%), non-transfusion dependent (74.9%), and had hemoglobin levels of 8-10 g/dL (56.3%) and ring sideroblasts <5% (59.3%). Most patients (68.0%) experienced ESA failure, with a median of 56.0 days from ESA initiation to failure, and a median of 466.5 days receiving ESA treatment after failure. Hematologic improvement was observed in 33.7% of patients.

CONCLUSIONS:

In this real-world evaluation of ESA treatment in a population with LR-MDS, only one-third of patients experienced hematologic improvement and two-thirds of patients remained on ESA treatment for ≥1 year after failure. These results demonstrate high rates of ESA failure and indicate patients in community oncology settings in the US may be continuing with ESA treatment despite failure.

31 Dec 2025·Hematology

Luspatercept for the treatment of lower-risk myelodysplastic syndrome with SF3B1 mutation: a real-world single-center research in China

Article

Author: Xiong, Youzhen ; Zhao, Yufei ; Zhou, Kang ; Zhao, Xin ; Li, Yuan ; Peng, Guangxin ; Hu, Xiangrong ; Fan, Huihui ; Li, Jianping ; Liu, Xu ; Xing, Lingxiao ; Hu, Jing ; Ye, Lei ; Zhang, Li ; Yang, Wenrui ; Zhang, Baohang ; Liang, Weiru ; Zhang, Fengkui ; Jing, Liping ; Kang, Rui ; Shi, Yimeng ; Yang, Yang

BACKGROUND:

Luspatercept, approved by the FDA and EMA for patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) unresponsive to erythropoiesis-stimulating agents (ESAs), lacks extensive real-world data, particularly in China.

METHODS:

We retrospectively analyzed 14 LR-MDS-SF3B1 patients treated with luspatercept for ≥12 weeks.

RESULTS:

Median age was 60 years (range 47-72); 42.9% were male. Before treatment, 78.6% were transfusion-dependent, and 42.9% had prior ESA therapy. At median 24-week follow-up (range 12-44), erythroid response rates were 71.43% (week 12), 75.00% (week 16), and 62.50% (week 24). Hemoglobin levels significantly improved at weeks 12 and 24 (P = 0.013, P = 0.005). No grade 3-4 adverse events occurred. Hematologic improvement-erythroid (HI-E) patients exhibited higher white blood cells, neutrophils, and reticulocytes at week 12 versus non-HI-E patients. Bone marrow analysis revealed erythroid hyperplasia in HI-E patients, with higher erythrocyte percentage (56.00% vs. 34.00%, P = 0.023), lower myeloid-to-erythroid ratio (0.60 vs. 1.59, P = 0.024), and increased polychromatic erythroblasts (19.50% vs. 10.00%, P = 0.034).

CONCLUSIONS:

Luspatercept demonstrated efficacy and safety in Chinese LR-MDSSF3B1 patients. Greater erythroid hyperplasia correlated with better clinical response.

186

News (Medical) associated with Luspatercept-AAMT

07 Dec 2025

·www.prnewswire.com

Rigel Presents Updated Data from the Ongoing Phase 1b Study Evaluating R289 in Patients with Lower-Risk MDS at the 67th ASH Annual Meeting and Exposition

R289 continues to be generally well tolerated and at doses of ≥500 mg QD preliminary efficacy was observed in elderly, heavily pre-treated lower-risk MDS patients RBC-TI was achieved by 33% (6/18) of evaluable transfusion dependent patients receiving R289 doses ≥500 mg QD, including 40% (2/5) in the 500 mg BID dose group SOUTH SAN FRANCISCO, Calif., Dec. 7, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced updated data from its ongoing Phase 1b study evaluating R2891, an oral prodrug of R835, a potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4), in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). The data are being presented today in an oral session by Dr. Guillermo Garcia-Manero at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 6-9, in Orlando, Florida and virtually. "New therapies are needed for patients with transfusion dependent lower-risk MDS. We're pleased to share these updated study results, which underscore the potential of R289 to become a treatment option for these patients," said Lisa Rojkjaer, M.D., Rigel's chief medical officer. "We look forward to concluding the dose expansion phase of the study and anticipate selection of the recommended Phase 2 dose for future clinical studies in the second half of 2026." Rigel's open-label Phase 1b study of R289 is evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with R/R lower-risk MDS (NCT05308264). Enrollment in the dose escalation phase of the study was completed in July 2025. In October 2025, the first patient was dosed in the dose expansion phase where up to 40 patients will be randomized to either 500 mg once or twice daily to determine the recommended Phase 2 dose for future clinical trials. Key highlights from the updated data as of October 28, 2025, include: 33 patients were enrolled, representing a difficult-to-treat population. The median age was 75. The median number of prior therapies was 3 (range: 1-8); 76% (25) of patients had received luspatercept, 73% (24) had received an erythropoiesis stimulating agent (ESA), 67% (22) had received an hypomethylating agent (HMA) and 6% (2) had received imetelstat. 61% (20) of patients were high transfusion burden (HTB) at baseline. 67% (22) of patients were ring sideroblast (RS) negative. Median duration of treatment was 5.5 months (range: 0.9 - 27.7 months). R289 was generally well tolerated across all dose groups in this heavily pre-treated lower-risk MDS patient population, the majority of whom were HTB at baseline. The most common Grade 1/2 treatment-emergent adverse events (TEAEs) (in ≥18% of patients) were diarrhea (n=10, 30%), constipation and fatigue (each n=9, 27%), and creatinine increased and cough (each n=7, 21%). The most frequent Grade 3/4 TEAEs were anemia (n=6, 18%), neutrophil count decreased and pneumonia (each n=5, 15%), and alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased (each n=3, 9%). One (1) dose limiting toxicity (DLT) (Grade 4 AST increased/Grade 3 ALT increased) was reported in the 750 mg dose group. For evaluable transfusion dependent (TD) patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 6/18 (33%) patients achieved durable red blood cell transfusion independence (RBC-TI) of >8 weeks [500 mg QD (1/3), 750 mg QD (2/5), 500/250 mg QD (1/5), 500 mg BID (2/5)]. Duration of RBC-TI was >16 weeks in 4 patients and >24 weeks in 3 patients. The median time to onset of RBC-TI was 1.9 months and the median duration of RBC-TI was 22.9 weeks. Peak hemoglobin increases of 2.9 to 6.1 g/dL compared to baseline occurred in patients achieving RBC-TI. Of the 6 patients achieving RBC-TI, 5 had received an HMA. At doses ≥500 mg QD, steady state R835 plasma concentrations reached or exceeded those associated with 50-90% inhibition of lipopolysaccharide (LPS)-induced cytokine release previously observed in healthy volunteers. Oral presentation details are as follows: Sunday, December 7, 2025, 9:45am to 10:00am ET Publication #: 489 Session Name: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Moving the Needle Through Novel Approaches in MDS and CMML Presentation Title: An Update of Safety and Efficacy Results from a Phase 1b Study of R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower Risk Myelodysplastic Syndrome (LR-MDS) Presenter: Guillermo Garcia-Manero, M.D. R289 was previously granted Orphan Drug designation for the treatment of myelodysplastic syndromes and granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS by the FDA. About R289 R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.2 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 South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. Sallman DA et al. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. Front Oncol. June 16, 2016. doi: Forward Looking Statements This press release contains forward-looking statements relating to, among other things, the potential outcomes of the dose escalation and expansion phase of the ongoing Phase 1b study of R289, the potential benefits of R289 as a therapeutic for MDS and lower-risk MDS, the existence of patients with an unmet medical need for such therapy, and Rigel's ability to further develop its clinical stage product candidates. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements and as such are intended to be covered by the safe harbor for "forward-looking statements" provided by the PSLRA. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "outcome", "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 Rigel's 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, the risks and uncertainties of clinical trials and drug development; risks and uncertainties associated with the commercialization and marketing of R289; risks that the FDA or other regulatory authorities may make adverse decisions regarding R289; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that R289 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2025 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 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. 21% more press release views with Request a Demo

Clinical ResultPhase 1Fast TrackOrphan DrugASH

07 Dec 2025

·www.rigel.com

Rigel Presents Updated Data from the Ongoing Phase 1b Study Evaluating R289 in Patients with Lower-Risk MDS at the 67th ASH Annual Meeting and Exposition

Consent Details [#IABV2SETTINGS#] About Necessary cookies help make a website usable by enabling basic functions like page navigation and access to secure areas of the website. The website cannot function properly without these cookies.Cision4Learn more about this providerc [x2]Used in order to detect spam and improve the website's security. Maximum Storage Duration: 6 monthsType: HTTP CookieINGRESSCOOKIE [x2]This cookie is used to distinguish between humans and bots. Maximum Storage Duration: SessionType: HTTP Cookie Cookiebot1Learn more about this providerCookieConsentStores the user's cookie consent state for the current domainMaximum Storage Duration: 1 yearType: HTTP Cookie Quotemedia1Learn more about this providerJSESSIONIDPreserves users states across page requests.Maximum Storage Duration: SessionType: HTTP Cookie c212.net hcaptcha.com 4__cf_bm [x4]This cookie is used to distinguish between humans and bots. 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Google2Learn more about this providerSome of the data collected by this provider is for the purposes of personalization and measuring advertising effectiveness. _gaRegisters a unique ID that is used to generate statistical data on how the visitor uses the website.Maximum Storage Duration: 2 yearsType: HTTP Cookie_ga_#Used by Google Analytics to collect data on the number of times a user has visited the website as well as dates for the first and most recent visit. Maximum Storage Duration: 2 yearsType: HTTP Cookie We do not use cookies of this type. Quotemedia4Learn more about this providerapp_93303_DayYearRangePendingMaximum Storage Duration: 1 dayType: HTTP Cookieapp_93303_DetailedQuoteTabPendingMaximum Storage Duration: 1 dayType: HTTP Cookieapp_93303_InteractiveChartPendingMaximum Storage Duration: 1 dayType: HTTP Cookieapp_93303_PriceHistoryPendingMaximum Storage Duration: 1 dayType: HTTP Cookie Home Who We Are Company Overview Management Team Board of Directors Partners Pipeline Clinical Programs IRAK1/4 RIPK1 Partnered Programs Clinical Trials Investigator Sponsored Research Expanded Access Policy Products Join Our Team Life at Rigel Our Values Benefits Current Openings Investors News & Events Contact Us Company Overview Management Team Board of Directors Partners Clinical Programs IRAK1/4 RIPK1 Partnered Programs Clinical Trials Investigator Sponsored Research Expanded Access Policy Life at Rigel Our Values Benefits Current Openings Overview News & Events Press Releases Events & Presentations Email Alerts Financial Info Financial Results Income Statement Balance Sheet Cash Flow FAQ Stock Data Quote Charts Historical Data SEC Filings All SEC Filings Annual Reports Quarterly Reports Section 16 Filings Analyst Coverage Governance Management Team Board of Directors Board Committees Governance Documents Press Releases Events & Presentations Email Alerts Financial Results Income Statement Balance Sheet Cash Flow FAQ Quote Charts Historical Data All SEC Filings Annual Reports Quarterly Reports Section 16 Filings Management Team Board of Directors Board Committees Governance Documents News & Events Press Releases Events & Presentations Email Alerts R289 continues to be generally well tolerated and at doses of ≥500 mg QD preliminary efficacy was observed in elderly, heavily pre-treated lower-risk MDS patients RBC-TI was achieved by 33% (6/18) of evaluable transfusion dependent patients receiving R289 doses ≥500 mg QD, including 40% (2/5) in the 500 mg BID dose group SOUTH SAN FRANCISCO, Calif., Dec. 7, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced updated data from its ongoing Phase 1b study evaluating R2891, an oral prodrug of R835, a potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4), in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). The data are being presented today in an oral session by Dr. Guillermo Garcia-Manero at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 6-9, in Orlando, Florida and virtually. "New therapies are needed for patients with transfusion dependent lower-risk MDS. We're pleased to share these updated study results, which underscore the potential of R289 to become a treatment option for these patients," said Lisa Rojkjaer, M.D., Rigel's chief medical officer. "We look forward to concluding the dose expansion phase of the study and anticipate selection of the recommended Phase 2 dose for future clinical studies in the second half of 2026." Rigel's open-label Phase 1b study of R289 is evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with R/R lower-risk MDS (NCT05308264). Enrollment in the dose escalation phase of the study was completed in July 2025. In October 2025, the first patient was dosed in the dose expansion phase where up to 40 patients will be randomized to either 500 mg once or twice daily to determine the recommended Phase 2 dose for future clinical trials. Key highlights from the updated data as of October 28, 2025, include: 33 patients were enrolled, representing a difficult-to-treat population. The median age was 75. The median number of prior therapies was 3 (range: 1-8); 76% (25) of patients had received luspatercept, 73% (24) had received an erythropoiesis stimulating agent (ESA), 67% (22) had received an hypomethylating agent (HMA) and 6% (2) had received imetelstat. 61% (20) of patients were high transfusion burden (HTB) at baseline. 67% (22) of patients were ring sideroblast (RS) negative. Median duration of treatment was 5.5 months (range: 0.9 - 27.7 months). R289 was generally well tolerated across all dose groups in this heavily pre-treated lower-risk MDS patient population, the majority of whom were HTB at baseline. The most common Grade 1/2 treatment-emergent adverse events (TEAEs) (in ≥18% of patients) were diarrhea (n=10, 30%), constipation and fatigue (each n=9, 27%), and creatinine increased and cough (each n=7, 21%). The most frequent Grade 3/4 TEAEs were anemia (n=6, 18%), neutrophil count decreased and pneumonia (each n=5, 15%), and alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased (each n=3, 9%). One (1) dose limiting toxicity (DLT) (Grade 4 AST increased/Grade 3 ALT increased) was reported in the 750 mg dose group. For evaluable transfusion dependent (TD) patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 6/18 (33%) patients achieved durable red blood cell transfusion independence (RBC-TI) of >8 weeks [500 mg QD (1/3), 750 mg QD (2/5), 500/250 mg QD (1/5), 500 mg BID (2/5)]. Duration of RBC-TI was >16 weeks in 4 patients and >24 weeks in 3 patients. The median time to onset of RBC-TI was 1.9 months and the median duration of RBC-TI was 22.9 weeks. Peak hemoglobin increases of 2.9 to 6.1 g/dL compared to baseline occurred in patients achieving RBC-TI. Of the 6 patients achieving RBC-TI, 5 had received an HMA. At doses ≥500 mg QD, steady state R835 plasma concentrations reached or exceeded those associated with 50-90% inhibition of lipopolysaccharide (LPS)-induced cytokine release previously observed in healthy volunteers. Oral presentation details are as follows: Sunday, December 7, 2025, 9:45am to 10:00am ET Publication #: 489 Session Name: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Moving the Needle Through Novel Approaches in MDS and CMML Presentation Title: An Update of Safety and Efficacy Results from a Phase 1b Study of R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower Risk Myelodysplastic Syndrome (LR-MDS) Presenter: Guillermo Garcia-Manero, M.D. R289 was previously granted Orphan Drug designation for the treatment of myelodysplastic syndromes and granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS by the FDA. About R289 R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.2 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 South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. Forward Looking Statements This press release contains forward-looking statements relating to, among other things, the potential outcomes of the dose escalation and expansion phase of the ongoing Phase 1b study of R289, the potential benefits of R289 as a therapeutic for MDS and lower-risk MDS, the existence of patients with an unmet medical need for such therapy, and Rigel's ability to further develop its clinical stage product candidates. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements and as such are intended to be covered by the safe harbor for "forward-looking statements" provided by the PSLRA. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "outcome", "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 Rigel's 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, the risks and uncertainties of clinical trials and drug development; risks and uncertainties associated with the commercialization and marketing of R289; risks that the FDA or other regulatory authorities may make adverse decisions regarding R289; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that R289 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2025 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: David Rosen Argot Partners 646.461.6387 david.rosen@argotpartners.com View original content to download multimedia:https://www.prnewswire.com/news-releases/rigel-presents-updated-data-from-the-ongoing-phase-1b-study-evaluating-r289-in-patients-with-lower-risk-mds-at-the-67th-ash-annual-meeting-and-exposition-302634716.html SOURCE Rigel Pharmaceuticals, Inc. Email Alerts RSS News Feed

Clinical ResultPhase 1Fast TrackASHOrphan Drug

03 Dec 2025

·www.fiercebiotech.com

With site \'irregularities,\' Bristol Myers delays key Cobenfy readout in Alzheimer\'s psychosis

With a newly announced delay, Bristol Myers Squibb looks to finish 2025 without a much-needed comeback story for Cobenfy after another clinical setback this spring.\n The phase 3 comeback story Bristol Myers Squibb investors were eagerly anticipating is not to be—at least not this year.The highly anticipated Adept-2 study will not read out by year-end as previously planned after BMS identified “irregularities due to clinical trial execution at a small number of study sites,” the company said Wednesday.Adept-2 is one of three phase 3 trials in which BMS is testing its blockbuster hopeful Cobenfy in psychosis associated with Alzheimer’s disease.With the delay, BMS looks to finish 2025 without a much-needed comeback story for Cobenfy after another trial flop this spring for the drug as an adjunctive treatment for schizophrenia. More broadly, out of the six pivotal trials BMS has read out this year, only one success was booked on one of the dual primary endpoints in a multiple myeloma trial of iberdomide.Alzheimer’s psychosis is a large market, as BMS estimates about half of the 6 million U.S. patients with Alzheimer’s suffer from hallucinations and delusions.Investors have high expectations for Adept-2 “given the size of the market opportunity, need for momentum in the Cobenfy clinical trial launch, and recent setbacks with other late-stage programs at Bristol Myers,” William Blair analysts pointed out in a Dec. 3 note. Investors first got anxious about Adept-2 after executive comments made during BMS’ second-quarter earnings call in July. At that time, BMS’ then-chief medical officer Samit Hirawat, M.D., said the New Jersey pharma was conducting trial site reviews of Adept-2 as part of an effort to improve success for all BMS clinical programs.Now, with the reviews having identified “irregularities,” BMS has decided to exclude patient data from those sites. Following agreement with the FDA, an independent party conducted an interim data analysis of both efficacy and safety while BMS remained blinded to study data. At the recommendation of the data monitoring committee, BMS will start enrolling new patients into Adept-2, which is now expected to read out by the end of 2026. The company’s Adept-1 and Adept-4 trials are expected to read out by the end of next year as originally planned, the company said.Because BMS has said that at least two positive trials are required for a filing for approval, the Adept-2 delay alone does not impact the company’s original regulatory plan.While site irregularities and a delay might raise concerns, the William Blair team deemed the data monitoring committee’s recommendation to continue the trial as a positive sign, because, they wrote, “if there was no signal, why bother increasing enrollment?”The affected sites are located in the U.S., according to William Blair analysts who spoke with BMS’ investor relations team. The company is not disclosing the number of patients affected nor the exact nature of the irregularities, other than explaining that the situation involved a multitude of issues, according to William Blair. The study previously closed enrollment after reaching 400 patients, according to ClinicalTrials.gov.Those sites’ data will also be excluded from Adept-1 and -4 if they participated in those parallel Cobenfy studies, according to the analysts.“Our decision to exclude patient data from sites where irregularities were observed reflects our unwavering commitment to safeguarding the integrity of our studies,” Laura Gault, M.D, Ph.D., who heads up neuroscience drug development at BMS, said in a Dec. 3 statement. “Psychosis related to Alzheimer’s Disease remains an area of tremendous unmet medical need, and maintaining rigorous standards is essential as we work to identify innovative treatment options for patients and families affected by this devastating condition.” BMS needs several wins to instill confidence in its growth potential for 2030 and beyond. Besides Cobenfy’s flop as an adjunctive schizophrenia treatment, the company also recorded phase 3 failures this year for Opdualag, Camzyos, Reblozyl and, most recently, Johnson & Johnson-partnered factor XIa inhibitor milvexian.Hirawat stepped down amid the string of trial setbacks and was recently succeeded by AstraZeneca veteran Cristian Massacesi, M.D.

$With site \'irregularities,\' Bristol Myers delays key Cobenfy readout in Alzheimer\'s psychosis$

Phase 3Phase 2Clinical Trial FailureClinical Trial Termination

100 Deals associated with Luspatercept-AAMT

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KEGG	Wiki	ATC	Drug Bank
-	Luspatercept-AAMT	B03XA06	DB12281

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Non-transfusion dependent thalassaemia	European Union	Bristol-Myers Squibb Pharma EEIG	20 Mar 2023
Non-transfusion dependent thalassaemia	Iceland	Bristol-Myers Squibb Pharma EEIG	20 Mar 2023
Non-transfusion dependent thalassaemia	Liechtenstein	Bristol-Myers Squibb Pharma EEIG	20 Mar 2023
Non-transfusion dependent thalassaemia	Norway	Bristol-Myers Squibb Pharma EEIG	20 Mar 2023
Anemia	South Korea	Bristol Myers Squibb Co.	09 May 2022
Anemia, Sideroblastic	European Union	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Anemia, Sideroblastic	Iceland	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Anemia, Sideroblastic	Liechtenstein	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Anemia, Sideroblastic	Norway	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Myelodysplastic Syndromes	European Union	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Myelodysplastic Syndromes	Iceland	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Myelodysplastic Syndromes	Liechtenstein	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Myelodysplastic Syndromes	Norway	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion dependent anaemia	European Union	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion dependent anaemia	Iceland	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion dependent anaemia	Liechtenstein	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion dependent anaemia	Norway	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion-dependent Beta Thalassemia	European Union	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion-dependent Beta Thalassemia	Iceland	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020
Transfusion-dependent Beta Thalassemia	Liechtenstein	Bristol-Myers Squibb Pharma EEIG	25 Jun 2020

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Myelofibrosis	Phase 3	China	Celgene Corp.	23 Feb 2022
Polycythemia Vera	Phase 3	China	Celgene Corp.	23 Feb 2022
Thrombocythemia, Essential	Phase 3	China	Celgene Corp.	23 Feb 2022
Post-polycythemia vera myelofibrosis	Phase 3	United States	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	China	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	Japan	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	Argentina	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	Australia	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	Austria	Celgene Corp.	25 Feb 2021
Post-polycythemia vera myelofibrosis	Phase 3	Belgium	Celgene Corp.	25 Feb 2021

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04717414 (Independence, NEWS) Manual	Phase 3	Anemia \| Myelofibrosis	-	Reblozyl	ipafgksvov(aqlfjqxhoo): P-Value = 0.0674 Not Met	Negative	18 Jul 2025
				Placebo
ASCO2025	Not Applicable	Myelodysplastic Syndromes	2,614	Luspatercept	mldezspcfy(kojaupokfm) = fcgnftvrcr ywwxtndywc (xrftupyjyq, 31.7 - 60.2) View more	Positive	30 May 2025
				Placebo	mldezspcfy(kojaupokfm) = bkkmgjmduf ywwxtndywc (xrftupyjyq, 60.7 - 74.0) View more
NCT03682536 (COMMANDS, ASCO2025)	Phase 3	myelodysplastic anemia First line ESA-naive \| LR-MDS	-	Luspatercept	gattdqffom(jdwvnhvrmi) = vevqmhzdip wwcvpkgpuo (qtlrmfrbqb ) View more	Positive	30 May 2025
				Epoetin alfa	gattdqffom(jdwvnhvrmi) = rgaltjwfnt wwcvpkgpuo (qtlrmfrbqb ) View more
COMMANDS trial (ASCO2025)	Not Applicable	Myelodysplastic Syndromes First line	103	Luspatercept	aairvzkmhz(mftfqloqfl) = fsdzifkobb eqldidgwvo (spqzdmtifm ) View more	Positive	30 May 2025
				Erythropoiesis-stimulating agents	aairvzkmhz(mftfqloqfl) = fgrjefnfna eqldidgwvo (spqzdmtifm ) View more
NCT03682536 (COMMANDS, EHA2025)	Phase 3	Myelodysplastic Syndromes First line erythropoiesis stimulating agent (ESA)-naive \| transfusion-dependent (TD)	-	Luspatercept	mroqnviegv(ghzlvbjfxg) = etqwgmymtf ajprunzrcx (ccqmjhoszx ) View more	Positive	22 May 2025
				Epoetin alfa	mroqnviegv(ghzlvbjfxg) = bujdxwprxy ajprunzrcx (ccqmjhoszx ) View more
NCT03682536 (COMMANDS, Pubmed \| Adv Ther)	Phase 3	Myelodysplastic Syndromes	-	Luspatercept	zufmlfbgma(chmeqseciw) = Rates of treatment-emergent adverse events, including asthenia and hypertension, generally decreased over time in both arms zdfzymcsfc (ajqkfnqewm ) View more	Positive	16 May 2025
				Epoetin alfa
PB2756 (EHA2025)	Not Applicable	Myelodysplastic Syndromes First line ring sideroblast (RS) level \| serum erythropoietin	103	Luspatercept	dwhhojefeu(aehtveneth) = tnnbyoabxk tfnhyokprf (djbkypifck )	Positive	14 May 2025
				Erythropoiesis-Stimulating Agents	dwhhojefeu(aehtveneth) = hkoqgayuku tfnhyokprf (djbkypifck )
NCT03682536 (COMMANDS, EHA2025)	Phase 3	Myelodysplastic Syndromes	350	Luspatercept	smazpuclet(slqeeqgnqs) = jqpuozflcg detgypmnbi (ghtdcxlpzl ) View more	Positive	14 May 2025
				Epoetin Alfa	smazpuclet(slqeeqgnqs) = uhdgmjpirq detgypmnbi (ghtdcxlpzl ) View more
PS2186 (EHA2025)	Not Applicable	Beta-Thalassemia	15	Luspatercept 1.0 mg/kg	yxiwvhaiiy(qqvnrzhclp) = The most common side effect was bone pain in the first 2-3 cycles of treatment aycksilokt (xhutvewemf )	-	14 May 2025
PB3537 (EHA2025)	Not Applicable	-	28	Luspatercept 1.0 mg/kg SC Q3W	mhyxfmtehu(pthrdewgju) = xsuhabdebo lebtoldpie (eqlqddnlse )	Positive	14 May 2025

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