inclacumab (PF-07940370) / Roche, Pfizer, Genmab - LARVOL DELTA

crizanlizumab and inclacumab are equally potent inhibitors of cell adhesion in the blood of patients with sickle cell disease. (PubMed, Blood Red Cells Iron) - "In summary, these results suggest that comparable or higher inhibition of cell adhesion with crizanlizumab vs inclacumab does not correlate with P-selectin binding affinity. Ultimately, clinical trials are required to evaluate how crizanlizumab vs inclacumab translate into treatment outcomes in SCD patients."

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

Circulating Platelet-Natural Killer Cell Complexes are Elevated in People Living with HIV on Antiretroviral Therapy. (PubMed, J Leukoc Biol) - "Notably, this correlation diminished following monoclonal antibody treatment with inclacumab, which inhibits P-selectin-dependent platelet interactions. We propose that the chronic activation of platelets during HIV infection fosters platelet interactions with NK cells in PWH on ART, ultimately contributing to NK cell dysfunction."

Journal • Human Immunodeficiency Virus • Infectious Disease • IFNG • IL2RA • NKG2D

Hypoxia-induced regulations of cell adhesion molecules and their implications for pathogenesis, diagnosis, and treatment of endometriosis. (PubMed, Front Mol Biosci) - "Within this group, P-selectin emerges as a particularly promising candidate, as its association with disease-related inflammatory activity supports its potential utility as a non-invasive biomarker and as a therapeutic target, exemplified by preclinical studies using the monoclonal antibody inclacumab...Furthermore, therapeutic strategies targeting adhesion-related pathways - either directly or through modulation of hypoxia-responsive signaling - have demonstrated promising results in preclinical studies. This review highlights cell adhesion molecules as central effectors of hypoxia-driven mechanisms in endometriosis and underscores their relevance for the development of mechanism-based diagnostic and therapeutic approaches, complementing existing hormonal and symptomatic treatments."

Journal • Review • Endometriosis • Gynecology • Inflammation • Women's Health • CDH1 • CDH2 • HIF1A • ICAM1 • MMP9

Discontinued therapies for sickle cell disease: status and future directions. (PubMed, Expert Opin Investig Drugs) - "Over the past decade, the therapeutic landscape for sickle cell disease (SCD) has expanded beyond hydroxyurea to targeted small molecules, monoclonal antibodies, and transformative cellular and gene therapies...Recent advances in sickle cell therapies bring real promise alongside setbacks. Failures are part of progress, but better trial design, transparency, patient partnership, and shared data can reduce harm, strengthen trust, and ensure innovation translates into meaningful, durable patient benefit."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Aggregation of Platelets and Human EGFR Mutant Lung Adenocarcinoma Cells Under Flow Is Governed by Shear Accumulation. (PubMed, Microcirculation) - "These results indicate that platelet-PC-9 aggregation is governed by a shear accumulation-dependent mechanism, optimized under moderate shear and finite exposure, and regulated by P-selectin and CD40L. These findings provide new biophysical insights into transient platelet-PC-9 interactions in circulation and suggest that targeting platelet activation pathways or modulating hemodynamics may prevent hematogenous metastasis."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CTCs • EGFR

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=242 | Terminated | Sponsor: Pfizer | N=147 ➔ 242 | Trial completion date: Nov 2028 ➔ Nov 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2028 ➔ Nov 2025; Sponsor decision to terminate study based on results of parent study GBT2104-131.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Population Pharmacokinetic Modeling of Different Formulations of Inclacumab Using Phase 1 Data in Healthy Participants (ASH 2023) - "The PopPK of IV inclacumab in healthy participants was described by a 3-compartment disposition model with parallel linear and nonlinear clearances. Estimated relative exposure of Roche v0. 2 and GBT-manufactured inclacumab was similar, indicating comparability in drug exposure."

Clinical • P1 data • PK/PD data • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Inclacumab Reduce Preexisting Red Blood Cell Adhesion to Activated Endothelial Cells: In-Vitro Assessment of the Microfluidic Platform Endothelium-on-a-Chip (ASH 2023) - "Inclacumab is able not only to prevent the adhesion of RBCs to acutely and chronically activated HUVECs but is able to remove the preexisting adhesion and results in significant higher reduction compared to untreated. RBCs adhesion assay on Endothelium-on-a-chip is a novel and efficient way to study the efficacy of the new antiadhesive drug and could be used to monitor patient response to new therapies in SCD. Figure1: Effect of Inclacumab vs Crizanlizumab on removal of SCD RBC adhesion to heme activated HUVECs."

Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Pfizer Inc…announced results from the Phase 3 THRIVE-131 study evaluating inclacumab, an investigational P-selectin inhibitor, in patients 16 years of age and older with sickle cell disease (Pfizer Press Release) - "The study did not meet its primary endpoint of significant reduction in the rate of vaso-occlusive crises (VOCs) in participants receiving inclacumab versus placebo every 12 weeks over 48 weeks. Inclacumab was generally well tolerated in THRIVE-131. The most commonly reported treatment-emergent adverse events in either group were anemia, arthralgia, back pain, headache, malaria, sickle cell anemia with crisis, and upper respiratory tract infection."

P3 data • Sickle Cell Disease

Differential Expression of lncRNAs in Ovarian Tissue of Meigu Goats During the Sexually Immature and Mature Periods. (PubMed, Curr Issues Mol Biol) - "Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these target genes were associated with various biological processes and pathways pertinent to ovarian development, including reproduction, reproductive process, JAK-STAT signaling pathway, progesterone-mediated oocyte maturation, Wnt signaling pathway, and cytokine-cytokine receptor interaction. Furthermore, lncRNA-mRNA interaction network analysis suggested that MSTRG.15120.9 and MSTRG.15110.2 play crucial regulatory roles in ovarian development. This study provides a valuable resource for elucidating the molecular regulatory mechanisms of lncRNAs in ovarian tissue during the sexual maturity period in goats."

Journal

Mean platelet volume and total white cell count as Diagnostic and Management Markers in sickle cell (ISTH 2025) - "All SCA patients were on B-complex, folic acid, and vitamin C; 86% were on hydroxyurea, and 7% each on inclacumab and vexeletor. Mean platelet volume (MPV: 9.59 fL) and platelet distribution width (PDW: 11.79 fL) were significantly lower (p<0.05) in SCA patients compared to controls (MPV: 10.12 fL; PDW: 12.92 fL). Differences in TWBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils were statistically signi Table or Figure Upload"

Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Thrombocytopenia

Functional Outcomes of Platelet NK Cell Complexes in People Living with HIV (IMMUNOLOGY 2025) - "In Rhesus macaques (RMs), treatment with inclacumab (INC) was given before and after SIV infection, and NK cell phenotypes and functions were monitored...Platelet-NK interactions lead to NK activation and cytotoxicity, potentially leading to NK dysfunction over time. These findings may inform future therapeutic strategies where platelet inhibitors could reduce chronic NK activation.Keywords: Animals Human Non-Human Primate; Cells Natural Killer Cells; Processes Cell Activation Cell Differentiation"

Human Immunodeficiency Virus • Infectious Disease • CD14 • IL2RA • NKG2D

Activated Platelets Render Functionally Deficient Natural Killer Cells in People Living With HIV (CROI 2025) - "Furthermore, Rhesus macaques (RMs) were treated with vehicle (n=5) or inclacumab, (n=5) at week -1 and week 2 post-infection and infected with SIV on day 0...In vitro, platelet-NK co-cultures confirm the formation of PNKCs, and both in vitro and in vivo studies implicate platelets as drivers in NK dysfunction. These results have important consequences on future immune cell therapeutics in which the inclusion of platelet inhibitors may enhance cure outcomes."

Human Immunodeficiency Virus • Infectious Disease • CD14 • CD69 • IL2RA • NCR1 • NKG2D

THRIVE-131: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=243 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

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

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=108 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=520 ➔ 108

Enrollment change • Enrollment closed • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=72 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; Study was terminated due to poor accrual and associated recrutiment challenges

Trial termination • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=72 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

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

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Recruiting | Sponsor: Pfizer | Enrolling by invitation ➔ Recruiting

Enrollment status • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Enrolling by invitation | Sponsor: Pfizer | Trial primary completion date: Mar 2027 ➔ Nov 2028

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

THRIVE-131: A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=229 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2023 ➔ Aug 2024

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

THRIVE-132: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (clinicaltrials.gov) - P3 | N=67 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=280 ➔ 67

Enrollment change • Enrollment closed • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A phase 1 study in healthy participants to characterize the safety and pharmacology of inclacumab, a fully human anti-P-selectin antibody, in development for treatment of sickle cell disease. (PubMed, Eur J Clin Pharmacol) - "Inclacumab was well tolerated, with PK as expected for a monoclonal antibody against a membrane-bound target and a long duration of PD effects after both single IV doses, supporting a prolonged dosing interval."

Journal • P1 data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

IN VITRO COMPARISON OF THE EFFECTS OF INCLACUMAB VS CRIZANLIZUMAB ON REDUCING ENDOTHELIAL ADHESION OF RED BLOOD CELLS IN STANDARDIZED MICROFLUIDIC PLATFORM (EHA 2023) - "Inclacumab reduces the levels of RBCs adhesion to chronic and acute heme activated HUVECs compared to untreated samples and treated with Crizanlizumab, using in vitro microfluidic system. Endothelium-on-a-chip microfluidic platform is a novel system that can be used as companion in new drug efficacy study and could be used to monitor patient response to anti-adhesive therapies in SCD Sickle cell, Sickle cell adhesion, Red blood cell, Sickle cell disease"

Preclinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

TRIALS IN PROGRESS: THE THRIVE STUDIES EVALUATING THE EFFICACY, SAFETY, AND LONG-TERM TREATMENT WITH INCLACUMAB, A P-SELECTIN INHIBITOR, IN PATIENTS WITH SICKLE CELL DISEASE (EHA 2022) - P3 | "Results Recruiting for both THRIVE-131 and THRIVE-132 began in October 2021 and is ongoing. Conclusion The THRIVE-131 and THRIVE-132 phase 3 studies will examine the efficacy of inclacumab in reducing VOCs and readmissions due to VOCs, and the THRIVE-133 OLE study will examine the long-term safety of inclacumab in individuals with SCD."

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

A Study to Evaluate the Long-term Safety of Inclacumab Administered to Participants With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=520 | Enrolling by invitation | Sponsor: Global Blood Therapeutics | Trial completion date: Mar 2027 ➔ Nov 2028

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