OxyDial

Free Heme Impairs Macrophage Function and Exacerbates Tissue Damage in Sickle Cell Disease New research published in the journal Blood has found that sickle cell disease (SCD) leads to altered macrophage function due to heme associated with hemolysis. This alteration results in defective efferocytosis and worsens the inflammatory response to tissue damage. Researchers suggest that restoring macrophage function through heme scavengers or PGC1α/PPARγ modulation could be a potential therapeutic strategy to prevent persistent inflammation, aggravated tissue damage, and autoimmunity in SCD. In the study, murine models of SCD were used to investigate the mechanisms behind heme-mediated defective efferocytosis and changes in macrophage function. The exposure to heme altered the response of macrophages to apoptotic cell damage, leading to excessive inflammatory cell recruitment and defective efferocytosis. This not only exacerbated tissue damage but also sustained inflammation. Mechanistic studies revealed that heme activation of TLR4 signaling suppressed the transcription factor PPARγ and its coactivator PGC1α, which impaired mitochondrial dynamics and biogenesis. Heme-exposed macrophages were unable to switch to fatty acid β-oxidation and ATP production, resulting in reduced anti-inflammatory cytokine secretion. However, when heme-exposed macrophages were treated with heme scavengers or through PGC1α/PPARγ modulation, inflammation was counteracted, tissue damage resolution was improved, and apoptotic cell clearance was restored. The research also showed that patient plasma impaired the phagocytic capacity of bone marrow-derived macrophages, which improved with treatment using heme scavengers, PPARγ agonists, or interleukin-4 (IL-4). The results demonstrate the potential therapeutic benefit of restoring macrophage function in SCD to ameliorate tissue damage, inflammation, and autoimmune diseases. Read more: https://lnkd.in/erUiut8d #SickleCellDisease #MacrophageFunction #Efferocytosis #Inflammation #TissueDamage #Autoimmunity #HemeScavengers #PGC1α #PPARγ #TherapeuticStrategy #ImmuneResponse #MitochondrialDynamics #CytokineSecretion #PhagocyticCapacity #IL4

Agios Completes Enrollment for Sickle Cell Disease Trial The Phase 3 RISE UP trial has marked a significant step in addressing sickle cell disease (SCD). Agios Pharmaceuticals has completed enrollment for this pivotal study. The trial is assessing the potential of mitapivat, an experimental oral drug, to effectively treat SCD in individuals aged 16 and older. Over 200 participants are participating in this global study, which will evaluate key factors such as hemoglobin response and the frequency of sickle cell pain crises over a year. Agios is optimistic about the study, expecting to share topline results in late 2025. Mitapivat's approach involves enhancing the energy mechanisms within red blood cells, aiming to reduce the tendency of sickling, a critical challenge in SCD management. Dr. Sarah Gheuens, the Chief Medical Officer at Agios, thanked everyone involved for their indispensable contributions to the trial's progress. At OxyDial, we're inspired by Agios's dedication to combating SCD and advancing patient care in rare blood disorders. The completion of this trial enrollment underscores the crucial role of continued research and collaboration in improving the lives of those living with complex conditions. Read more: https://lnkd.in/eQKvnJUg #AgiosPharma #SickleCellDisease #RISEUPTrial #Mitapivat #HematologyResearch #RareDiseases #ClinicalTrials

Zydus and ICMR Launch Trial for New Sickle Cell Disease Treatment Zydus Group and Indian Council of Medical Research (ICMR) have announced a collaboration to begin testing a new medicine for sickle cell disease. They're initiating a Phase 2 trial of a drug called Desidustat to evaluate its potential in treating this serious blood condition. Key points of the trial: ✅ Phase 2 study to assess Desidustat's safety and efficacy ✅ Will examine the drug's impact on patients' hemoglobin levels ✅ Aims to reduce the need for blood transfusions and painful crises The partnership between Zydus and ICMR highlights the importance of public-private collaboration in developing new treatments for challenging diseases. This trial represents a significant step towards finding innovative therapies for sickle cell disease, which affects millions of people worldwide. At OxyDial, we're encouraged by Zydus and ICMR's progress in advancing Desidustat as a potential new treatment option for patients living with sickle cell disease. The initiation of this Phase 2 trial represents an important step in developing innovative therapies that could improve disease management and quality of life for those impacted by this challenging blood disorder. We look forward to seeing the results of this study and its potential impact on the field of hematology. Read more: https://lnkd.in/gRFyjSEz #SickleCellTrial #Desidustat #ZydusICMRLabo #HopeForSickleCell #PublicPrivateCure #HematologyBreakthrough

Mitem Pharma Acquires Worldwide Rights to Desferal from Novartis In a strategic move within the hematology field, French pharmaceutical company MITEM Pharma has successfully acquired the global rights to Desferal (deferoxamine) from Novartis. Desferal, an essential medicine listed by the World Health Organization (WHO), is a vital injectable treatment widely utilized for managing iron overload conditions resulting from blood transfusions in patients with beta-thalassemia and sickle cell anemia. Supported by TechLife Capital, Groupe Macsf, and additional investments from Access Capital Partners and SWEN Capital Partners, this acquisition not only underscores Mitem Pharma’s growth strategy but also reinforces its international expansion and dedication to ensuring the most effective solutions for rare blood disorders. At OxyDial, we believe this acquisition marks a significant advancement in the treatment of beta-thalassemia and sickle cell anemia. This development highlights the continuous progress in hematology research and underscores the importance of sustained clinical efforts in enhancing patient care for rare diseases. Read more: https://lnkd.in/eU68ibaD #MitemPharma #Desferal #Hematology #IronOverload #BetaThalassaemia #SickleCellAnemia #ClinicalResearch #RareDiseases #MedicalAdvancements

Luspatercept Outperforms Epoetin Alfa in Phase III COMMANDS Trial for MDS Anemia The phase III COMMANDS trial has revealed a massive development in treating myelodysplastic syndromes (MDS). According to the primary analysis, Luspatercept, developed by Acceleron Pharma, demonstrated superior efficacy to epoetin alfa in anemia management. The trial, involving 363 ESA-naive adults with transfusion-dependent, very low- to intermediate-risk MDS, showed that 60% of patients receiving luspatercept achieved red blood cell transfusion independence, compared to 35% with epoetin alfa. Lead author Dr. Matteo G Della Porta from Humanitas Research Hospital in Milan, Italy, stated that luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk MDS. The safety profile revealed hypertension and anemia as the most common grade 3-4 adverse events for luspatercept, with pneumonia being the most frequent serious adverse event in both treatment groups. At OxyDial, we're thrilled by these promising results, which mark a significant advancement in MDS treatment. This trial highlights the ongoing progress in hematology research but emphasizes the critical importance of continued clinical investigations to enhance patient care in rare blood disorders. Read more: https://lnkd.in/e8Yi8FGD #Luspatercept #MDS #COMMANDS #ClinicalTrial #HematologyResearch #AnemiaTreatment

New Agios Pharma MDS Treatment Gains FDA 'Orphan Drug' Status Agios Pharmaceuticals has reached a significant milestone in the development of their new myelodysplastic syndrome (MDS) treatment, Tebapivat, with the FDA's recent designation of the drug as an 'orphan drug'. Tebapivat has shown promise in treating lower-risk MDS, which affects between 75,000 and 80,000 patients in the US and EU each year. The 'orphan drug' status facilitates several benefits for Agios, including additional tax credits, FDA fee exemptions, and the potential for a seven-year market exclusivity period post-approval. Agios' Chief Medical Officer, Dr. Sarah Gheuens, emphasized the significance of this designation after Agios wrapped the Phase 2a study of Tebapivat; with the company now proceeding with Phase 2b of the trial. The OxyDial team is closely following Agios’ progress, with this designation not only highlighting the company's dedication to fighting rare hematologic diseases, but also helping set the stage for the potentially transformative impacts on disease management and patient care. Read more: https://lnkd.in/eKAWFzTf #AgiosPharma #Tebapivat #MDS #ClinicalTrial #HematologyResearch #OrphanDrugDesignation

Novo Nordisk Advances Etavopivat to Phase III Trial for Sickle Cell Disease Novo Nordisk has received Subject Expert Committee (SEC) approval from India's Central Drug Standard Control Organization (CDSCO) to conduct Phase III clinical trials of etavopivat in the treatment of sickle cell disease (SCD). The proposed trial will evaluate the oral medication, which is a small-molecule activator of erythrocyte pyruvate kinase (PKR) that has been developed as a treatment option for SCD and other hemoglobinopathies. This approval follows Novo Nordisk's presentation of the first version of the Phase III clinical trial (protocol No. NN7535-7807) from April of this year. Etavopivat aims to ameliorate the sickling of red blood cells in SCD patients through multiple mechanisms, including increasing oxygen-hemoglobin affinity and the preservation of red blood cell membrane integrity. At OxyDial, we're extremely interested in Novo Nordisk's progress and the development of etavopivat as a new treatment for SCD. The advancement to Phase III represents a significant step towards bringing these kinds of innovative new therapies to thousands of patients living with this challenging blood disorder. We're eager to see how etavopivat can help improve disease management and quality of life for those affected by SCD worldwide. Read more: https://lnkd.in/evkA_jaV #NovoNordisk #Etavopivat #SickleCellDisease #ClinicalTrial #HematologyResearch

Merck Advances Bomedemstat in Phase III Trial for Essential Thrombocythemia Pharmaceutical giant Merck has announced the start of the Phase III Shorespan-007 trial to evaluate bomedemstat (MK-3543) in approximately 300 essential thrombocythemia (ET) patients globally. The study is set to compare bomedemstat to hydroxyurea, the current standard-of-care; and the FDA has granted bomedemstat both the 'orphan drug' and 'fast track' designations for ET and myelofibrosis treatment. This Phase III trial, along with the ongoing Shorespan-006 study, aims to advance bomedemstat as a novel treatment option for patients living with this challenging myeloproliferative neoplasm. At OxyDial, we're encouraged by Merck's progress in developing bomedemstat as a potential new treatment option for patients living with this rare blood disorder. The initiation of this Phase III trial represents an important milestone in advancing innovative therapies that could improve disease control and quality of life for those impacted by essential thrombocythemia. Read more: https://lnkd.in/eiHZwezF #Merck #Bomedemstat #EssentialThrombocythemia #ClinicalTrial #HematologyResearch

Earlier Treatment with Luspatercept May Improve Patient Outcomes New data from the ongoing COMMANDS trial shows Bristol Myers Squibb's new myelodysplastic syndrome (MDS) drug, Luspatercept (Reblozyl) may significantly improve anemia in low-risk patients with MDS. The Director of Columbia University's MDS Center, Dr. Azra Raza, discussed these findings at a recent Case-Based Roundtable event, where the study found that 76.4% of luspatercept-treated patients were able to achieve red blood cell transfusion independence for more than 12 weeks, compared to 55.8% of patients treated with standard erythropoiesis-stimulating agents over the same period. Dr. Raza highlighted luspatercept's longer-lasting effects, with a median of 155 days to the first post-treatment transfusion compared to 42 days for ESAs. At OxyDial, we're encouraged by luspatercept's potential to transform anemia management in MDS. This research opens new avenues for reducing transfusion dependency and improving the quality of life for patients with this challenging hematological condition. Read more: https://lnkd.in/eAgxSdrn #MDS #Luspatercept #Anemia #BristolMyersSquibb #HematologyResearch

Agios Pharmaceuticals Advances Therapies for Rare Blood Disorders Agios Pharmaceuticals continues to make remarkable strides in the development of new treatments for rare blood disorders. The company's latest quarterly report for Q2 2024 showcases impressive progress for several diseases: ▪️ Thalassemia: Positive Phase 3 ENERGIZE and ENERGIZE-T study results for mitapivat in all thalassemia subtypes ▪️ PK Deficiency: Promising topline data from Phase 3 ACTIVATE-KidsT study - first safety and efficacy data in children ▪️ Sickle Cell Disease: Nearing completion of enrollment in Phase 3 RISE UP study for mitapivat Key milestones for 2024: ▪️ File sNDA for mitapivat in thalassemia by End of Year. ▪️ Complete enrollment for sickle cell disease Phase 3 study ▪️ Potential PYRUKYND® launches in thalassemia and sickle cell disease At OxyDial, we're inspired by Agios' commitment to treating rare blood disorders. Their work on mitapivat across multiple indications shows dedication to improving patients' lives. We applaud their efforts to advance treatment options for thalassemia, PK deficiency, and sickle cell disease. Read more: https://lnkd.in/eCzdCafE #AgiosPharma #RareBloodDisorders #Thalassemia #PKDeficiency #SickleCellDisease #ClinicalTrials