Adakveo (crizanlizumab-tmca) / Novartis - LARVOL DELTA

The Role of Pediatric Clinicians in the Diagnosis, Management, and Referral of Priapism in Children and Adolescents with Sickle Cell Disease. (PubMed, Pediatr Clin North Am) - "Nearly half of the patients with recurrent priapism failed to present to the hospital due to poor understanding of the clinical implications of the complication. This article discusses the role of pediatric clinicians in diagnosing and managing priapism."

Journal • Review • Erectile Dysfunction • Genetic Disorders • Hematological Disorders • Pain • Pediatrics • Sickle Cell Disease

Association between comorbid depression and antidepressant adherence with adherence to disease-modifying therapies in patients with sickle cell disease in Texas Medicaid (ASH 2025) - "Additionally, patients with SCD and comorbiddepression had a significantly higher proportion of patients with a diagnosis of anxiety (76.6% vs. 16.5%)and serious mental health conditions (31.8% vs. 4.0%) during the study period.Among patients with SCD, mean adherence for each SCD DMT was: 38.7±26.7% (hydroxyurea),37.5±29.5% (L-glutamine), 33.9±30.4% (crizanlizumab), and 60.9±34.1% (voxelotor). The prevalence of depression among patients with SCD is high and associated with loweradherence to SCD DMTs. Antidepressant-adherent patients were more likely to adhere to SCD DMTs. SCDproviders should regularly screen for depression, initiate depression treatment when appropriate, andencourage adherence to antidepressants, as this may improve adherence to SCD DMTs and overallhealth outcomes for this population."

Adherence • Clinical • Medicaid • Reimbursement • US reimbursement • CNS Disorders • Depression • Genetic Disorders • Hematological Disorders • Mood Disorders • Psychiatry • Sickle Cell Disease

Reassessing voxelotor safety and efficacy: Real-world outcomes from the ASH research collaborative data hub (ASH 2025) - "DMT use wasdefined as EHR-reported treatment with hydroxyurea, voxelotor, or L-glutamine for ≥90 days/year.Transfusions were categorized as DMT if ≥6 occurred/ year. Crizanlizumab was excluded due toinsufficient data...In conclusion, the ASH RC Data Hub is a valuable resource for post-marketingpharmacovigilance studies. Independent analyses can complement industry data, providing additionalvalue through increased transparency and more comprehensive dataset."

Clinical • Real-world • Real-world evidence • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • TINCR

A phase 2 open-label study of epeleuton in patients with sickle cell disease (ASH 2025) - P2 | "Concomitant treatment with a stable doseof hydroxyurea, crizanlizumab or l-glutamine is permitted during the study. A therapy that can simultaneously impact multiple hallmark features of SCD including RBC morphologyand function as well as cellular adhesion may have an important disease-modifying utility for patientswith SCD. The results of this study are anticipated to confirm the potential of epeleuton to impact rates ofVOC, multiple aspects of SCD pathophysiology, and to guide the design and conduct of a phase 2/3 studyin patients with SCD"

Clinical • P2 data • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease

Description of neurocognition in adult sickle cell disease patients using the NIH toolbox (ASH 2025) - "Similarly, no differences were noted in scores between participants taking Hydroxyurea orCrizanlizumab and those who were not. Adult SCD patients have lower neurocognition scores in all domains using the NIH toolboxcognitive battery of tests when compared to the age-matched normal controls. To our knowledge, we arethe first to report serial neurocognition testing in non-pediatric SCD patients that suggests that diseaseseverity, assessed by degree of anemia and ACS, lowers neurocognition. We believe that this testingapproach can be incorporated into clinical practice."

Clinical • Anemia • Beta-Thalassemia • Cardiovascular • Cognitive Disorders • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

IHP-102 compound decreases the adhesion of sickle cell disease RBCs to acutely activated endothelial cells in biochip labs endothelial-on-a-chip assay (ASH 2025) - "IHP-102 inhibits RBC adhesion to acutely activated HUVECs across a diverse dosagespectrum from 100μg/mL down to 1μg/mL. These results further support its potential as an acutetreatment for VOE and are a first demonstration of its activity in human SCD donor blood. Our findingsindicate that IHP-102 exhibits increased effectiveness when the baseline adhesion level is elevated due toheterogeneity in SCD."

Genetic Disorders • Hematological Disorders • Sickle Cell Disease

The weight of stress: Allostatic load as a predictor of vaso-occlusive episodes in adults with sickle cell disease (ASH 2025) - "The association with hospitalization remained nonsignificant.To explore potential confounders, we conducted a multivariate logistic regression analysis including fetalhemoglobin (HbF) levels and therapy status (hydroxyurea, voxelotor, or crizanlizumab). Our preliminary findings suggest that the AL index is a feasible and practical tool forassessing cumulative stress burden in adults with SCD, as it relies on biomarkers routinely collected inclinical care. This pilot study provides early evidence that higher AL is independently associated withincreased VOE frequency and ED utilization. Incorporating AL into clinical assessments may help identifyhigh-risk individuals who could benefit from disease-modifying therapy."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HBB

Hibiscus 2 (Trial-in-Progress): A global, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease (ASH 2025) - P3 | "Study population: PwSCD of any genotype and aged ≥12 years are eligible if they have moderate-to-severe anemia, Hb ≥5.0–≤10.0 g/dL at screening, and 2–15 VOC episodes in the year before screening.Concomitant hydroxyurea and/or L-glutamine use is permitted if PwSCD have received stable dosing andare compliant with treatment before screening. Key exclusion criteria are chronic transfusion therapy,use of erythropoiesis-stimulating agents, voxelotor, or crizanlizumab before starting study intervention,and hepatic dysfunction...Study status HIBISCUS 2 is enrolling participants at sites in Australia, Belgium, Brazil, Canada, Colombia, France,Ghana, Greece, India, Italy, Kenya, Lebanon, the Netherlands, Nigeria, Oman, Saudi Arabia, Spain, Turkey,Uganda, the United Kingdom, and the United States. The results from this confirmatory study will provideadditional evidence that etavopivat has the potential to delay or prevent VOCs, enhance Hb levels, andreduce fatigue in PwSCD."

Clinical • P3 data • Anemia • Genetic Disorders • Hematological Disorders • Hepatology • Sickle Cell Disease

Thrombotic outcomes in sickle cell disease patients treated with crizanlizumab with or without hydroxyurea: A real-world retrospective cohort analysis using the trinetx database (ASH 2025) - "A total of 1,816 patients met the inclusion criteria, with 908 in each matched cohort. The mean age was29.7 years in the crizanlizumab group and 29.6 years in the control group, with a similar femalepredominance (61.3% vs. 60.8%)."

Real-world • Real-world evidence • Retrospective data • Genetic Disorders • Hematological Disorders

A randomized, double-blind, placebo-controlled trial of a novel BTK inhibitor (rilzabrutinib) in patients with sickle cell disease (SCD) aged 10–65 years: LIBRA Study (ASH 2025) - P3 | "Additionally, participants may beon hydroxyurea and/or L-glutamine (if treated ≥6 months, on a stable dose ≥3 months, with ≥1 VOC whileon stable dose); those not receiving these medications must not plan to initiate them during the study.Key exclusion criteria include a history of stroke or abnormal transcranial doppler, and the use ofcrizanlizumab within 90 days and/or voxelotor within 30 days prior to screening. Other endpoints include change from baseline in QoL, patient globalimpression of fatigue and health status, and biomarkers (biomarkers of inflammation, endothelialactivation, and oxidative stress). This study aims to address a significant unmet need in SCD by evaluatingrilzabrutinib as a novel potential treatment option to reduce VOC burden and improve outcomes in SCD."

Clinical • Anemia • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Immune Modulation • Immunology • Inflammation • Pediatrics • Sickle Cell Disease • Thrombosis • HBB

Maternal and fetal risks in patients with sickle cell disease: Results of the retrospective drepamom study (ASH 2025) - "Beforepregnancy, 39% of patients were receiving baseline treatment, mainly hydroxyurea (HU) in 77% of cases(discontinued in 67% within 3 months after pregnancy diagnosis), and transfusion programs in 23%(alone or combined with HU and/or Crizanlizumab)...Acetylsalicylic acid did not reduce the prevalence of placental abnormalities (p=1) norincrease the risk of postpartum hemorrhage (p=0.637). ConclusionPregnancy in sickle cell disease carries significant maternal and fetal risks and requires management inspecialized centers. Transfusion programs reduce the risk of VOC but must be balanced againstalloimmunization and delayed hemolytic transfusion reactions risks, which is prevalent in this population,highlighting the need to reconsider therapeutic alternatives, including HU, in cases of transfusiondeadlock."

Retrospective data • Genetic Disorders • Gynecology • Hematological Disorders • Infectious Disease • Obstetrics • Sickle Cell Disease

Etavopivat in adolescents with sickle cell disease: Emerging safety and efficacy findings from the first cohort of the ongoing Phase 1/2 hibiscus kids study (ASH 2025) - P2 | "Stable dose concurrent therapy with hydroxyurea,crizanlizumab and L-glutamine was permitted.Safety endpoints included serious adverse events (SAEs), treatment-emergent adverse events (TEAEs),etavopivat discontinuations, dosing interruptions, and dose reductions. In this preliminary analysis of the HIBISCUS Kids study, the first to investigate a PKR activatorin a pediatric SCD population including children younger than 12 years, etavopivat was relatively welltolerated by adolescents. Cohort 1 enrollment and dosing are complete; weight-based dosing with agranule formulation has begun for cohort 2, children aged 6–<12 years. The study is expected to providefurther insights into the safety, tolerability, and potential clinical benefits of etavopivat in youngerchildren, including those as young as 6 months."

Clinical • P1/2 data • Anemia • Cholestasis • Fatigue • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Malaria • Pediatrics • Sickle Cell Disease

Interim analysis of a placebo controlled study of dronabinol for adults with sickle cell disease and chronic pain (ASH 2025) - "Mass spectrometry for minorcannabinoids was measured to assess for abstinence from other cannabinoids during the study period.30 subjects have been randomized (15 dronabinol/15 placebo), median age 34.3 SD 6.8 years old, 79%were female, 76% HbSS/HbSβ0, 24% HbSC/Hbβ+, 79% on hydroxyurea, 38% on crizanlizumab, and 41%on voxelotor (when it was available). In an interim analysis dronabinol was not associated with SAEs or worsened cognition, the onlyAEs were grade 1 and previously known. Personalized dose titration allowed those who were intolerantto side effects to withdraw early. Dronabinol improved social impact of disease."

Clinical • CNS Disorders • Fatigue • Genetic Disorders • Hematological Disorders • Neuralgia • Pain • Psychiatry • Sickle Cell Disease

Is hydroxyurea treatment associated with an increased risk of malignancy in sickle cell disease? a propensity-matched analysis of 27,854 patients in the real world (ASH 2025) - "Propensity scorematching was used to balance cohorts based on demographics, Charlson comorbidities, baselinehemoglobin levels, and other SCD-modifying therapies (e.g., crizanlizumab, voxelotor, L-glutamine). This comprehensive retrospective study found that the use of HU is associated with an increased risk ofboth hematologic and solid cancers in SCD, as well as higher mortality rates and increased healthcareutilization. This association remained significant among non-transfusion-dependent patients, suggestingthat disease severity alone may not fully explain these findings. MDS was the most common type ofhematological malignancy."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Sickle Cell Disease • Skin Cancer • Solid Tumor

Utilization and outcomes of erythropoietin stimulating agents in sickle cell disease patient: A real world data analysis (ASH 2025) - "The population was divided into two cohorts based on receipt of ESAs (EPO, Epoietin alfa,Darbepoetin alfa). Propensity Score matching (PSM) was carried to match age, sex, race, chronic heartfailure, chronic lung disease, neoplasms, chronic kidney disease stages 4 and 5, use of hydroxyurea andcrizanlizumab... This real-world data shows that ESAs use does increase the utilization of hydroxyurea, but itssignificance in improving survival and sickle cell crisis still needs to be evaluated with prognostic studies.The study also highlights potential risks of arterio-venous thrombosis with the use of ESAs."

Clinical • Real-world • Real-world evidence • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Genetic Disorders • Heart Failure • Hematological Disorders • Ischemic stroke • Myocardial Ischemia • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Sickle Cell Disease • Thrombosis

A phase III, multicenter, randomized, placebo controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult sickle cell disease patients with frequent vaso-occlusive crises: The sparkle study (ASH 2025) - P3 | "Participantswill log pain episodes via smartphones or a web portal at onset and will remain open until they reportresolution or seek medical assistance, after which data will be transferred to the electronic capturesystem.Patient recruitment is ongoing, with approximately 315 participants expected to enroll. Study completionis anticipated by 2030.In conclusion, the SPARKLE study may offer valuable insights into the clinical effectiveness ofcrizanlizumab in reducing both HCP managed and total VOCs (HCP- and self-managed), offering analternative to current HU/HC therapies."

Clinical • P3 data • Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Sickle Cell Disease

Low bone mineral density and pain impact in adults with sickle cell disease. (PubMed, Blood Adv) - P=N/A | "In multivariate linear regression, lumbar spine BMD Z-scores significantly changed by +0.31, -0.29, -0.14, and -1.3 for every unit increase in hemoglobin, indirect bilirubin, and white blood cell count, and with Crizanlizumab use, respectively...Understanding how low bone density, with or without osteonecrosis, mediates SCD pain warrants further investigation. NCT05283148."

Journal • Addiction (Opioid and Alcohol) • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain • Osteoporosis • Pain • Sickle Cell Disease

Anesthetic Considerations in a Patient with Sickle Cell Disease (ASA 2025) - "This case report highlights a severe pain crisis following Crizanlizumab (Adakveo) infusion, resulting in prolonged intubation, ventilator dependence, tracheal injury, and pneumomediastinum requiring tracheostomy...Imaging revealed pneumomediastinum concerning for tracheal injury. Although the pneumomediastinum resolved, tracheostomy dependence persisted at the time of discharge."

Clinical • Addiction (Opioid and Alcohol) • Anesthesia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Cost-Effectiveness Analysis of Crizanlizumab in Sickle Cell Disease in Iran. (PubMed, Iran J Med Sci) - "Sensitivity analysis results demonstrate that even a 20% reduction in the price of crizanlizumab does not lead to its cost-effectiveness in Iran. Crizanlizumab administration in sickle cell disease is not found cost-effective in Iran, neither as a monotherapy nor added to hydroxyurea."

HEOR • Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

SOLACE-Kids: Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients (clinicaltrials.gov) - P2 | N=117 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Curative Therapies for Hemophilias and Hemoglobinopathies in Adults: Immune, Gene, and Stem Cell Approaches in a Global Context. (PubMed, Biomedicines) - "Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide."

Journal • Review • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Sickle Cell Disease • Transplantation

Spleen Tyrosine Kinase Inhibition Mitigates Hemin-Induced Thromboinflammation in an Organ-Specific Manner in Sickle Cell Mice. (PubMed, Arterioscler Thromb Vasc Biol) - "The recent withdrawal of promising therapies, such as the anti-P-selectin antibody Crizanlizumab and the hemoglobin polymerization inhibitor Voxelotor, highlights the urgent need for innovative approaches to alleviate VOC and thromboinflammation. On the contrary, increasing the dose exacerbated hemin-induced bleeding in the lungs due to the complete abolishment of platelet adhesion in the pulmonary microcirculation. These findings underscore the critical role of Syk in vascular thrombo-inflammation and hypoperfusion in SCD, suggesting that Syk inhibition is a promising strategy to reduce VOC, improve renal and pulmonary perfusion, and reduce organ damage."

Journal • Preclinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Pulmonary Embolism • Sickle Cell Disease • SYK

ADORE: Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients (clinicaltrials.gov) - P1/2 | N=45 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; Sponsor Decision

Trial termination • Myelofibrosis

Grandchildren of GRNDaD: Shifts in disease-modifying therapy at the adolescent transition in sickle cell disease. (PubMed, Br J Haematol) - "Of the 3169 active patients in GRNDaD, about 65% of subjects were on hydroxyurea (hydroxycarbamide; HU), and 2130 had SCA. For novel therapeutics, we examined use prior to voxelotor's removal from the market and prior to publication of the negative phase III trial of crizanlizumab. Voxelotor utilization in this cohort was three times that reported by claims data while crizanlizumab usage was nearly double, suggesting high-quality comprehensive sickle cell care could increase utilization of novel therapies."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Updated Review of Current Therapeutic Approaches for the Management of Sickle Cell Disease. (PubMed, Cardiovasc Hematol Disord Drug Targets) - "There are six Food and Drug Administration (FDA)-approved drugs, hydroxyurea, L-glutamine, crizanlizumab- TMCA, voxelotor, Casgevy, and Lyfgenia, that are used for the prophylaxis and treatment of serious complications of sickle cell disease. Ongoing research seeks to enhance treatment options and develop potential cures for SCD. This review attempts to present a comprehensive overview of the current therapeutic approaches and newly developed innovative medicines to combat and potentially eradicate SCD with an emphasis on their mechanisms, efficacy, and clinical implications."

Journal • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Pain • Sickle Cell Disease • Transplantation