Cablivi (caplacizumab-yhdp) / Sanofi - LARVOL DELTA

Caplacizumab as a pre-emptive therapy in thrombotic thrombocytopenic purpura: A proactive strategy to reduce morbidity (ASH 2025) - "All patients received plasma exchange (median 11 sessions (range 6-15), corticosteroids (median 40 days; range 25 - 45), rituximab (median of 4 doses; range 3 to 8) and CPZ (median of 28 doses (range 10 to 34)). Pre-emptive initiation of CPZ, guided by clinical judgment and validated international risk scores, appears to be a safe and effective strategy to avoid treatment delays and reduce morbidity and mortality when ADAMTS-13 testing is not readily available. Larger, prospective studies are warranted to strengthen the evidence base and support broader implementation of this approach."

Gynecology • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Septic Shock • Systemic Lupus Erythematosus • Thrombocytopenic Purpura

Easix, a new tool to predict response and refractoriness in immune-mediated thrombotic thrombocytopenic purpura (ASH 2025) - "Caplacizumab, combined with plasma exchange (TPE), corticosteroids (CE), and rituximab, has improved outcomes. Notably, higher baseline EASIX values strongly predicted refractoriness and were also associated with mortality. Despite the small sample size, these findings support its incorporation into routine monitoring and justify prospective validation for early risk stratification and potentially guide treatment intensity."

Cardiovascular • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

A rare case of influenza associated immune thrombotic thrombocytopenia purpura in a pediatric patient (ASH 2025) - "The traditional management of iTTP includes plasma exchange (PLEX) and immunosuppressive therapy, i.e. corticosteroids, and in some cases rituximab. This case adds to the limited but growing body of evidence supporting the potential role of caplacizumab in pediatric iTTP, including in patients as young as 2 years old. Early diagnosis and timely initiation of targeted therapy are critical to improving outcomes and reducing the risk of morbidity and mortality in this vulnerable age group."

Clinical • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Influenza • Nephrology • Pediatrics • Renal Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura • HP

Real-world one-month mortality and bleeding outcomes with caplacizumab in thrombotic thrombocytopenic purpura: A propensity-matched cohort study (ASH 2025) - "However, given the lack of granular clinical data, such ascontraindications to caplacizumab use, it is possible that patients who received TPE alone wereinherently at a higher risk. As such, while these findings support the potential benefit of earlycaplacizumab use, they should be interpreted with caution and warrant prospective validation to confirmcausality and assess long-term outcomes."

Clinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Maternal and fetal outcomes in immune-mediated thrombotic thrombocytopenic purpura: A scoping review (ASH 2025) - "In 3pregnancies, FFP was used instead of TPE, Rituximab was used in 19 (7 antepartum) and caplacizumabwas used in 6 (2 antepartum) cases of ITTP.Of pregnancies with antepartum iTTP or with a hx of iTTP (n=182), fetal outcomes were available in 161pregnancies. Pregnancy in patients with a diagnosis of iTTP carries significant associated morbidity andmortality. To our knowledge, this is the most comprehensive report on fetal mortality. With 28.6% of fetaldemise, it is significantly higher than the fetal mortality in the general population (5.5 fetal deaths per1000 live births)."

Review • Hematological Disorders • Thrombocytopenic Purpura

Review of the management of patients with immune thrombotic thrombocytopenic purpura with persistently low adamts-13 activity - a challenge beyond rarity. (ASH 2025) - "7 patients were treated with caplacizumab and 1 with recombinantADAMTS13...Different immunosuppressive treatment combinations per patient: 2 patients: Corticosteroids+AntiCD201 patient: Corticosteroids+AntiCD20+Splenectomy4 patients: Corticosteroids+AntiCD20+Mycophenolate1 patient:Corticosteroids+AntiCD20+Mycophenolate+Daratumumab 1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomid1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomib+Splenectomy1 patient: Corticosteroids+Anti-CD20+Cyclosporine+Bortezomib+Mycophenolate.CONCLUSIONS - A small proportion of patients with iTTP don´t respond to first-line therapy and these individuals are athigh risk of relapse. A total of 11 patients meeting the specified criteria were identified, 7 women and 4 men. At diagnosis, the mean age was 43 years (range: 24–71). Laboratory parameters at presentation were:mean hemoglobin 9 g/dL (range: 6.5–12.7), mean platelet count 13.3 × 10³/mm³ (range: 5–22), and..."

Clinical • Review • Hematological Disorders • Thrombocytopenic Purpura • PROCR

Trends in acute TTP mortality amidst a shifting therapeutic landscape (ASH 2025) - "From 2010, all patients received rituximab with acute episodes. Over more than 2 decades, the proportion of deaths attributed to acute TTP episodes in alarge tertiary referral center has consistently declined across treatment eras, coinciding with sequentialadoption of modern therapeutics. Notably, no patients treated with caplacizumab in their acute coursehas died in the modern treatment era. Importantly, our data also shows that over 50% of TTP-relateddeaths occurred after a median follow up 4.4 years with 25% occurring after 13 years."

Hematological Disorders • Thrombocytopenic Purpura

Daratumumab for immune-mediated thrombotic thrombocytopenic purpura (iTTP): Results from the international, multicenter darttp study (ASH 2025) - "Patients had received a median of 3 (IQR 2)previous IST, including rituximab (100%), bortezomib and mycophenolate (25% each), cyclosporine andcyclophosphamide (20% each), azathioprine (15%), vincristine (10%), obinutuzumab, ofatumumab, andsplenectomy (5% each). Seventeen patients received daratumumab in the remission phase (i.e., forADAMTS13 relapse or intolerance to other IST), while 3 during an acute episode (plasma-based therapyand caplacizumab ongoing in 3 and 2 patients, respectively)...Disease duration, previous IST used, daratumumab schedule, ordemographics did not correlate with response or its duration...A patient not receiving acyclovir had a grade 2 zoster skininfection 3 months after her last daratumumab infusion. in this study, daratumumab warranted rapid ADAMTS13 remission in 75% of iTTP patientsrefractory or intolerant to rituximab and other conventional IST... in this study, daratumumab warranted rapid ADAMTS13 remission in 75% of iTTP patientsrefractory..."

Clinical • Cardiovascular • Dermatology • Hematological Disorders • Herpes Zoster • Thrombocytopenic Purpura • CD20

High morbidity and early readmissions in thrombotic thrombocytopenic purpura requiring intensive care: Insights from a national database (ASH 2025) - "TTP admissions were more common in females and characterised by a median patient age of 48 years.Critical care admissions for TTP are associated with high morbidity, frequent cardiovascular and renalcomplications, and substantial mortality despite widespread plasmapheresis use. Early readmission ratesremain considerable, highlighting the need for improved post-discharge care and strategies to reduceearly rehospitalizations. Further, the limited utilization of Caplacizumab highlights potential gaps inadopting newer therapies."

Acute Kidney Injury • Cardiovascular • Critical care • Hematological Disorders • Infectious Disease • Ischemic stroke • Myocardial Infarction • Nephrology • Novel Coronavirus Disease • Renal Disease • Thrombocytopenic Purpura • Ventricular Tachycardia

Stability of ADAMTS13 activity in liquid plasma and its clinical application in therapeutic plasma exchange for thrombotic thrombocytopenic purpura (ASH 2025) - "All patients received corticosteroids and rituximab; 8 patients inthe LP group also received caplacizumab. Its adjunct use in TPE for iTTP was not associated with increased bleeding and mortality. Thesefindings support the safety and effectiveness of LP as a complementary option to TP in the managementof iTTP, offering greater flexibility in emergent care and contributing to reduced product waste."

Clinical • Hematological Disorders • Thrombocytopenic Purpura

Inflammatory biomarkers in immune thrombotic thrombocytopenic purpura (iTTP): Focus on citrullinated H3 histone, tumor necrosis factor-alpha, and interleukin-6. (ASH 2025) - "As first-line treatment, all patients received daily TPE,immunosuppression (including rituximab), and caplacizumab. Our data show significant reductions in H3Cit and TNF-α during treatment, paralleling hematologic andbiochemical recovery. This suggests that such biomarkers may serve as indicators of NET-driveninflammation and immune activation. The positive correlation between TNF-α and anti-ADAMTS13antibodies further supports the link between inflammation and the autoimmune process in iTTP.Additionally, our preliminary data suggest that early initiation of caplacizumab may be associated withreduced inflammatory markers."

Biomarker • Cardiovascular • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Immunology • Infectious Disease • Myelodysplastic Syndrome • Thrombocytopenic Purpura • Thrombosis • HP • IL6 • TNFA

Caplacizumab as a single agent without plasma exchange in relapsed and refractory thrombotic thrombocytopenic purpura: A systematic review. (ASH 2025) - "This first systematic synthesis focuses on caplacizumab without plasma exchange in relapsed andrefractory TTP, where PEX is contraindicated or unavailable. Our findings suggest that caplacizumab, withor without steroids and rituximab, can achieve rapid clinical and hematologic remission in select patients,offering a potentially life-saving option. These findings reinforce the evolving treatment landscape whereplasma exchange may no longer be the default."

Review • Cerebral Hemorrhage • CNS Disorders • Cytomegalovirus Infection • Hematological Disorders • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Ischemic stroke • Nephrology • Novel Coronavirus Disease • Renal Disease • Thrombocytopenic Purpura

Embolic stroke of undetermined source with low ADAMTS13 level without evidence of microangiopathic hemolytic anemia- case series from single center experience (ASH 2025) - "There was no difference in ADAMTS13 level, ADAMTS13inhibitor titer, indirect bilirubin, haptoglobin, liver enzyme levels, reticulocyte and lymphocyte countbetween groups.Plasmapheresis was used in 6 episodes, 5 received steroids, 9 received rituximab and 1 receivedcaplacizumab. In addition to conventional antiplatelet therapy all thepatients received TTP directed therapy. Early recognition of high-risk patients during ADAMTS13 relapsewithout hematologic relapse is crucial as preemptive therapy such as caplacizumab in addition toADAMTS13 inhibitor eradication might be warranted in this group of patients."

Clinical • Anemia • Diabetes • Dyslipidemia • Genetic Disorders • Hematological Disorders • Hypertension • Ischemic stroke • Metabolic Disorders • Thrombocytopenic Purpura • HP

Real world outcomes in patients with acquired thrombotic thrombocytopenic purpura (TTP) treated with caplacizumab (ASH 2025) - "Rituximab is given to target antibody producing B-cells. There is no difference in incidence of thrombus formation, ICU admission and mortalitybetween SOC and Caplacizumab. Factors regarding real world use of caplacizumab should be exploredfurther to improve outcomes."

Clinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • HP • TNNI3

Mortality in immune TTP remains unpredictable: Shortcomings of prediction models despite machine learning advances (ASH 2025) - "We calculated sensitivity, specificity, positivepredictive value (PPV), and negative predictive value (NPV) based on the previously defined cut-offs of4.27% and 9.08% mortality risk in the original model, which categorized patients into standard risk, highrisk, and very high risk of predicted mortality.ResultsThe external validation cohort included 103 patients with confirmed iTTP and 11 deaths (10.7% mortalityrate).The USTMA Mortality Index demonstrated poor performance with AUC of 0.69 (95% CI, 0.55–0.83) in thevalidation cohort. The wide confidence interval reflects substantial uncertainty in model performance,ranging from poor to excellent, and is likely due to the small number of deaths.At a risk threshold ≥4.27%:Sensitivity = 64%Specificity = 70%PPV = 20%NPV = 94%At a risk threshold ≥9.08%:Sensitivity = 18%Specificity = 87%PPV = 14%NPV = 90%ConclusionThe USTMA Mortality Index demonstrated poor performance in the external validation cohort (AUC= 0.69, 95% CI,..."

Machine learning • Hematological Disorders • Thrombocytopenic Purpura

An updated systematic review and meta-analysis of caplacizumab for immune thromboticthrombocytopenic purpura: Insights into efficacy and safety (ASH 2025) - "This updated meta-analysis, incorporating both RCTs and real-worldstudies, provides the most comprehensive evidence to date on the efficacy and safety of caplacizumab iniTTP. The results confirm significant clinical benefits, including reduced TPE requirements, faster plateletrecovery, lower mortality, and shorter hospital stays. Moreover, early initiation was associated with morefavorable outcomes compared to delayed use."

Retrospective data • Review • Cardiovascular • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Fixed-duration preemptive rituximab maintenance over two years in recurrent thrombotic thrombocytopenic purpura with low ADAMTS13: A single-center case series (ASH 2025) - "Current treatment includes therapeutic plasma exchange, glucocorticoids,caplacizumab, and anti-CD20 rituximab. Fixed-interval rituximab maintenance every 3 months for 2 years appeared feasible and welltolerated in a small cohort of patients with recurrent iTTP and persistently low ADAMTS13 activity. Amongthe three evaluable patients, all achieved ADAMTS13 remission, and all four patients remained relapse-free during follow-up. While limited by sample size, this case series suggests that a proactive,standardized approach may offer clinical benefit compared to reactive or ADAMTS13-guided regimens.Prospective studies are warranted to validate efficacy, optimize treatment duration, evaluate cost-effectiveness, and refine patient selection criteria for this approach."

Clinical • Hematological Disorders • Infectious Disease • Thrombocytopenic Purpura

Cva with undetectable ADAMTS13 without hemolysis: An atypical presentation of thrombotic thrombocytopenic purpura (TTP) (ASH 2025) - "The patient was initiated on therapeuticplasma exchange and received steroids, caplacizumab and rituximab, resulting in partial improvement ofher neurological symptoms and normalization of ADAMTS13 activity. This case series underscores a diagnostically challenging subset of TTP in which patients present withacute neurological deficits and thrombocytopenia, but without laboratory evidence of hemolysis. Theseatypical presentations may delay diagnosis and management. Clinicians should maintain a high index ofsuspicion for TTP in similar clinical scenarios."

Cardiovascular • Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Ischemic stroke • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • HP

Thrombotic thrombocytopenic purpura-related mortality trends among the United States population: A retrospective study using the CDC wonder database (ASH 2025) - "While survival has improved significantly due to plasmaexchange, high-dose corticosteroids, rituximab, and ADAMTS13 testing, contemporary nationwide dataon TTP-related mortality trends remain limited. Persistent disparities by sex, race, age, and geography highlight theneed for targeted public health interventions. Ongoing national surveillance and equity-focused efforts,including expanded access to advanced therapeutics, are critical to reduce preventable TTP-relateddeaths, especially as novel therapies (e.g., caplacizumab) become more widely adopted."

Retrospective data • Thrombocytopenic Purpura

Splenectomy as a treatment for relapsed or refractory immune thrombotic thrombocytopenic purpura: A systematic review (ASH 2025) - "All patients received PLEX prior to splenectomy, oftenalongside corticosteroids, dextran, vincristine, and oral antiplatelet therapies. Splenectomy leads to a high rate of iTTP remission and is associated with low mortality,suggesting that it may be a reasonable therapeutic option in resource-limited settings where otheradjunctive therapies such as rituximab and caplacizumab are inaccessible. Conclusions are limited byheterogeneity with respect to disease and response definitions, and high risk of publication bias."

Review • Cardiovascular • Hematological Disorders • Infectious Disease • Respiratory Diseases • Thrombocytopenic Purpura

Caplacizumab for pediatric immune thrombotic thrombocytopenic purpura: A scoping review of current evidence (ASH 2025) - "Median treatment duration was 33.5 days (range 14–97).Corticosteroids and rituximab were given in 97% and 92% of patients, respectively. Caplacizumab appears to be both effective and well-tolerated in pediatric iTTP. It was associated withrapid platelet recovery, relatively short hospitalization, and high remission rates, with no reportedtreatment-related deaths or major bleeding. Notably, many patients were treated off-label below theEMA-approved age or weight thresholds, highlighting the clinical need despite regulatory limitations.Treatment duration and dosing varied across cases, reflecting the absence of standardized pediatricprotocols."

Clinical • Review • Cardiovascular • Hematological Disorders • Pediatrics • Renal Disease • Thrombocytopenic Purpura • Thrombosis

Cablivi (caplacizumab-yhdp) Real-World Evidence in 1,000+ Patients: Early Initiation Matters (ASH 2025) - "Supported By Sanofi For in-person participants onlyThis session will include a patient perspective"

Clinical • HEOR • Real-world • Real-world evidence

Tailored Treatment of Acute Immune-Mediated Thrombotic Thrombocytopenic Purpura (ASH 2025) - "A particular focus will be on the nanobody caplacizumab and how it has changed therapeutic strategies in iTTP. It will expand on the prerequisites and logistic challenges of iTTP therapy without the use of therapeutic plasma exchange, patient identification, procedures, and protocols. It will ultimately discuss current limitations and future directions of iTTP-therapy in the light of recent real-world data and case series."

Hematological Disorders • Thrombocytopenic Purpura

The Changing Landscape of the Care of Patients With Immune-Mediated and Congenital TTP (ASH 2025) - "Supported By C Thrombotic thrombocytopenic purpura (TTP), once almost universally fatal, is now a condition with markedly improved survival due to advancements in diagnostics, therapeutic plasma exchange, immunosuppressive therapies, and novel therapies like caplacizumab and recombinant ADAMTS13...He will discuss the integration of caplacizumab, corticosteroids, rituximab, and other emerging agents, including strategies to balance rapid disease control with long-term remission goals...Beyond this, Dr. Taylor will discuss how we need to examine what clinical outcomes we are targeting beyond prevention of acute TTP relapse."

Clinical • Cardiovascular • Cognitive Disorders • Hematological Disorders • Thrombocytopenic Purpura

The National Medical Products Administration (NMPA) in China has approved two innovative Sanofi medicines for rare hematologic diseases: Qfitlia (fitusiran) for hemophilia and Cablivi (caplacizumab) for acquired thrombotic thrombocytopenic purpura. (The Manila Times) - "Qfitlia is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in pediatric patients 12 years of age and older, and adults with severe hemophilia A (coagulation factor VIII deficiency, FVIII). This approval is based on data from the ATLAS phase 3 studies...Cablivi is the first Nanobody targeted therapy designed to treat acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) in adults and adolescents aged 12 or older weighing at least 40 kg."

China approval • Hemophilia A • Immune Thrombocytopenic Purpura