Adakveo (crizanlizumab-tmca) / Novartis - LARVOL DELTA

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

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

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

Crizanlizumab for Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL) (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Aug 2027 ➔ Dec 2025 | Trial primary completion date: Jan 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • CNS Disorders • Retinal Vasculopathy with Cerebral Leukoencephalopathy

PEOPLE WITH SICKLE CELL DISEASE EXPERIENCE SUBSTANTIAL SYMPTOM IMPACT DESPITE TREATMENT: FINDINGS FROM THE GLOBAL LISTEN SURVEY (EHA 2025) - "Data for impact of symptoms are reported as the proportion of PwSCD who responded that symptoms have a substantial effect on daily life (responses of "very much" or "a lot") and as a subanalysis by self-reported current SCD treatments: hydroxyurea (HU) only or other treatments (l-glutamine, voxelotor, or crizanlizumab) with or without HU.Overall, 1,145 PwSCD (58% female) with a median age of 30 years completed the LISTEN Survey. Despite the use of HU and other treatments, clinical features of SCD such as fatigue, depressive symptoms, and pain disrupt the lives of PwSCD, and VOCs continue to be experienced regularly. Therefore, more effective treatments are needed to address the unmet needs in managing the impact of SCD."

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

INDIVIDUAL PATIENT ADHESIVE PHENOTYPES DEFINED BY FLOW ADHESION OF WHOLE BLOOD TO P-SELECTIN PREDICTS BIOLOGIC RESPONSE TO CRIZANLIZUMAB ADMINISTERED IN THE REAL WORLD CLINICAL SETTING (EHA 2025) - "FA-WB-Psel assessment is feasible at a population scale in real-world settings. Only 41% of steady state patients are above the critical threshold for FA-WB-Psel (50 cells/mm²) and show statistically significant biologic responses to criz. However, only 21% had a complete biologic response to achieve FA-WB-Psel values below the critical threshold."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • SELP

Rollover Study for Patients With Sickle Cell Disease Who Have Completed a Prior Novartis-Sponsored Crizanlizumab Study (clinicaltrials.gov) - P4 | N=130 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2031 ➔ Jun 2031 | Trial primary completion date: Oct 2031 ➔ Jun 2031

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Identifying risk factors for chronic kidney disease progression in sickle cell disease. (ERA 2025) - "Sixteen patients (53.3%) were treated with hydroxyurea, and 4 patients (13%) participated in clinical trials (etavopirat, crizanlizumab). A significant proportion of patients with sickle cell disease present with glomerular hyperfiltration, and a notable number experience rapid renal function decline, particularly among men, homozygous patients, and those with vaso-occlusive crises. These findings underline the need for prospective studies to analyze the potential benefits of nephroprotective therapies that could improve the natural course of renal disease associated with sickle cell disease."

Clinical • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease

Effect of P2Y12 Inhibitors, SGLT2 Inhibitors and P-Selectin Inhibitors on One-year Quality-of-Life Outcomes in Critically Ill Patients Hospitalized for COVID-19: A Pre-specified Secondary Analysis of the ACTIV4a Randomized Clinical Trial (ATS 2025) - "In this secondary analysis of a randomized controlled platform trial, P2Y12 inhibitors, SGLT-2 inhibitors, and crizanlizumab were not associated with significant improvement in one-year QoL outcomes among hospitalized COVID-19 patients. Reduced physical and mental health scores were observed across multiple groups, with predictors of diminished QoL including pre-infection respiratory disease, female sex, and ethnicity."

Clinical • HEOR • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Sleep Disorder

Prescribing Trends of Disease-Modifying Medications in Texas Medicaid Enrollees with Sickle Cell Disease (ISPOR 2025) - "Hydroxyurea remains the dominant DMT prescribed. The number of monthly users of L-glutamine, voxelotor, and crizanlizumab increased gradually; however, that number remains low."

Medicaid • Reimbursement • US reimbursement • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Patient Characteristics Associated with the Use of Newly Approved Disease-Modifying Therapy (DMT) for Sickle Cell Disease in Texas Medicaid (ISPOR 2025) - "OBJECTIVES: This study aimed to identify patient characteristics associated with the utilization of new DMTs, including L-glutamine, crizanlizumab-tmca, and voxelotor. Age and greater healthcare utilization (i.e., more outpatient visits, more VOC events, and previous use of hydroxyurea) indicating severe conditions were associated with use of newly approved DMTs."

Clinical • Medicaid • Reimbursement • US reimbursement • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis. (PubMed, Blood Adv) - P1/2 | "Forty-four patients were enrolled in Part 1 of the study of ruxolitinib in combination with siremadlin, rineterkib, sabatolimab, crizanlizumab, or NIS793. Overall, available data from ADORE suggest the feasibility and benefits of combining novel agents with ruxolitinib in patients with suboptimal response to ruxolitinib alone. This trial was registered at www.clinicaltrials.gov as #NCT04097821."

Journal • Hematological Disorders • Myelofibrosis • Neutropenia • Thrombocytopenia • GDF15

Evidence and gaps in clinical outcomes of novel pharmacologic therapies for sickle cell disease: A systematic literature review highlighting insights from clinical trials and real-world studies. (PubMed, Blood Rev) - "This systematic review aims to summarise the clinical outcomes of l-glutamine, crizanlizumab, and voxelotor in the treatment of sickle cell disease (SCD) based on clinical trials and real-world data and to identify any gaps in the observations. While some real-world studies have reported a decrease in VOCs and hospitalizations, the results are inconsistent and not conclusive. Further studies are needed to assess the impact of these novel therapies on end-organ-specific complications of SCD."

Clinical data • Journal • Real-world evidence • Review • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Unlocking Prognostic Potential: Biomarker Predictors of Admission and Length of Stay in Pediatric Sickle Cell Vaso-Occlusive Pain Crisis (PAS 2025) - "Data collected included demographical information (age, gender, race/ethnicity), clinical characteristics (sickle cell disease genotype), disease modifying therapies (hydroxyurea, chronic PRBC transfusions, Adakveo), vital signs obtained from the ED (oxygen saturation and blood pressure), laboratory investigations obtained from most recent outpatient hematology clinic visit and ED (particularly white blood cell count, hemoglobin, platelet count, absolute neutrophil count, reticulocyte count), and total length of hospital stay. A total of 100 patients were included in the study. There was a significant relationship (r = .242, p = .015) between systolic blood pressure at admission and length of stay. There was a significant negative correlation (r = - .217, p = .031) between admission hemoglobin and length of stay when controlling for steady state hemoglobin."

Biomarker • Clinical • Genetic Disorders • Hematological Disorders • Mood Disorders • Pain • Pediatrics • Sickle Cell Disease

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials. (PubMed, Adv Ther) - "Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials."

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

Clinically relevant clot resolution via a thromboinflammation-on-a-chip. (PubMed, Nature) - "Specifically, we observed that, in thromboinflammation, (1) early tissue plasminogen activator administration within 3 h directly improves endothelial barrier function; (2) prophylactic defibrotide and enoxaparin suppress microvascular thromboinflammation through endothelium-mediated mechanisms; and (3) combining enoxaparin with crizanlizumab reduces microvascular occlusion and protects endothelial function in sickle cell disease. These data introduce a paradigm in investigating the underlying mechanisms of thromboinflammatory clot resolution and conducting drug discovery thereof."

Journal • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • Thrombosis • ELANE

Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial. (PubMed, Lancet Haematol) - P3 | "The STAND study supports the safety and tolerability of crizanlizumab in the treatment of sickle cell disease. The primary analysis showed no significant difference in efficacy between crizanlizumab and placebo. Factors including the COVID-19 pandemic, global enrolment with varied patterns of health-care use and vaso-occlusive crisis management as well as the commercial availability of crizanlizumab might have influenced these results. The safety profile of crizanlizumab was consistent with that in previous reports, without new safety concerns."

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

Now where do we STAND with crizanlizumab? (PubMed, Lancet Haematol) - No abstract available

Journal

Accelerated Drug Approvals and Patient Trust: Impact of Voxelotor & Crizanlizumab for Sickle Cell Disease. (PubMed, Blood Adv) - "Crizanlizumab and voxelotor were several of the first drugs to receive FDA approval for sickle cell disease (SCD) since the approval of hydroxyurea in 1998. In addition, the impact of these events, without transparent messaging, potentially threatened the fragile trust that providers have more recently been able to build with the SCD population regarding the medical system and research. While there is a need for new therapies in SCD, we must prioritize both safety and efficacy, and maintain trust in this population."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial (Lancet Haematol) - P3 | N=258 | STAND (NCT03814746) | Sponsor: Novartis Pharmaceuticals | "Between July 26, 2019, and Aug 31, 2022, 252 patients were enrolled and treated. The primary analysis showed an adjusted annualised rate of vaso-occlusive crises of 2·49 (95% CI 1·90–3·26) in the crizanlizumab 5·0 mg/kg group, 2·04 (1·56–2·65) in the 7·5 mg/kg group, and 2·30 (1·75–3·01) in the placebo group. Ratios of adjusted annualised rates of vaso-occlusive crises leading to health-care visits were 1·08 (95% CI 0·76–1·55, p>0·999) for 5·0 mg/kg and 0·89 (0·62–1·27, p>0·999) for 7·5 mg/kg vs placebo. The incidence of adverse events was similar across treatment groups."

P3 data • Sickle Cell Disease