Xolremdi (mavorixafor) / X4 Pharma, Abbisko, Norgine, taiba - LARVOL DELTA

Dual Targeting of CXCR4 and CXCL12 by 1,2,4-Triazole Derivatives: A Computational Approach Against Lung Cancer Metastasis. (PubMed, Iran J Pharm Res) - "Docking studies against CXCR4 and CXCL12 indicated that D54 and D57 had more favorable predicted docking scores than mavorixafor (a CXCR4 inhibitor) and LIT-927 (a CXCL12 inhibitor)...Compounds D54 and D57 were computationally prioritized as promising 1,2,4-triazole derivatives targeting the CXCR4/CXCL12 axis for further investigation in lung cancer metastasis. However, their predicted toxicity, pharmacokinetic, and drug-likeness profiles revealed several limitations that warrant further optimization and experimental validation."

Journal • Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CXCL12

Targeting the PHB2-ACSL3 Lipid-Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer. (PubMed, Adv Sci (Weinh)) - "The therapeutic effect was abrogated by the ferroptosis inhibitor Liproxstatin-1, confirming ferroptosis dependence. Collectively, our findings define a PHB2-ACSL3 lipid-metabolic axis that drives ferroptosis escape and identify Mavorixafor repurposing as an immediately translatable strategy to overcome cisplatin resistance in treatment-refractory GC."

Journal • Gastric Cancer • Oncology • Solid Tumor • ACSL3 • PHB2

Cloud-based ligand-guided virtual screening with deep-learning-enhanced docking identifies a micromolar CXCR4 antagonist. (PubMed, Mol Divers) - "A set of 18,378 compounds was identified through AMD070-based similarity filtering (Tanimoto ≥ 0.2, ECFP4)...It reduced the viability of three colorectal cancer organoid strains in a dose-dependent manner (IC50 7.97-11.16 µM), providing supportive phenotypic evidence of activity in patient-derived organoid models. Overall, this end-to-end workflow efficiently compresses large libraries into a confirmed micromolar CXCR4 hit while lowering computational and infrastructure barriers for early-stage discovery."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CXCL12

Molecular interaction between AMD-070 with human serum albumin: insights from network pharmacology, multispectral technology and computer simulation. (PubMed, Bioorg Chem) - "Additionally, AMD-070 inhibits HSA esterase-like activity in a dose-dependent manner, likely via interaction with ARG257. These findings provide a biophysical characterization of the HSA-AMD-070 interaction, offering a molecular basis for understanding its plasma protein binding behavior."

Journal

A Study to Investigate Pharmacokinetics (PK) and Safety of a Single Dose of Mavorixafor in Participants With Hepatic Impairment (HI) Compared to Matched Healthy Volunteers With Normal Hepatic Function (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: X4 Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Hepatitis C • Hepatology • Liver Failure

Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome (clinicaltrials.gov) - P3 | N=31 | Completed | Sponsor: X4 Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Infectious Disease • CXCR4

A PIVOTAL PHASE 3 STUDY TO INVESTIGATE EFFICACY, SAFETY, AND TOLERABILITY OF MAVORIXAFOR IN PARTICIPANTS WITH PRIMARY CHRONIC NEUTROPENIA – TRIAL UPDATE (EHA 2026) - P3 | "J Clin Pathol . Aug 16 2024; 77(9):586-604."

Clinical • P3 data • Aplastic Anemia • Genetic Disorders • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lupus Nephritis • Metabolic Disorders • Musculoskeletal Pain • Myelodysplastic Syndrome • Nephrology • Neutropenia • Osteoporosis • Thrombocytopenia • Vasculitis • CSF3R • CXCR2 • CXCR4 • ELANE • GATA2 • SRP54

PRECLINICAL MODELING OF WHIM SYNDROME TO DEVELOP AN ADENINE BASE EDITING THERAPEUTIC APPROACH (ASGCT 2026) - "Treatment is conservative with immunoglobulin supplementation, administration of recombinant G-CSF or low-doses of the CXCR4 antagonists Plerixafor or Mavorixafor. Our results demonstrated that all three CXCR4-dependent functions were restored when WHIM-derived T cells were edited by ABE mRNA or protein, providing relevant proof of concept data. Conclusion Overall, our data show that the ABE strategy efficiently restores the WT CXCR4 sequence in both murine and human haematopoietic cells at a molecular and functional level, encouraging further development and holding promise as a valuable therapeutic option for the correction of CXCR4-R334X HSPCs in patients affected by WHIM syndrome."

Preclinical • Gene Therapies • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Primary Immunodeficiency • B2M • CXCL12 • PTPRC

Structure-Guided Repurposing of Approved Drugs Identifies Aprepitant and Mavorixafor as Putative δ-Opioid Receptor Agonist Candidates. (PubMed, Int J Mol Sci) - "Both compounds formed stable receptor-ligand complexes, maintained persistent interactions with Asp128, promoted contraction of the orthosteric pocket, and retained favorable redocking scores on the MD-refined receptor conformations. Overall, these results identify aprepitant and mavorixafor as promising putative DOR agonists and provide a rational foundation for their experimental validation through binding, functional, and in vivo pain studies in the future."

Journal • Pain

Mavorixafor, An Oral CXCR4 Antagonist, Allows for G-CSF Dosage Reduction in Chronic Neutropenia (ASPHO 2026) - "The majority of participants and investigators were willing to substantially reduce or discontinue G-CSF use with mavorixafor treatment. The study included two pediatric participants who were able to decrease G-CSF while maintaining clinically targeted ANC levels. Future studies are required to understand the optimal timing and pace of G-CSF dosage reduction and drivers of patient/provider willingness to reduce or eliminate G-CSF use."

Hematological Disorders • Infectious Disease • Neutropenia

X4 Pharmaceuticals Announces European Commission Approval of XOLREMDI (Mavorixafor), the First and Only Authorized Treatment for Patients with WHIM Syndrome in the European Union (The Manila Times) - "The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP)....The EC approval is supported by results from the pivotal Phase 3 4WHIM trial, a global, randomized, double-blind, placebo-controlled, 52-week multicenter study that evaluated the efficacy and safety of mavorixafor in 31 people aged 12 years and older diagnosed with WHIM syndrome."

EMA approval • Rare Diseases

Immune modulatory activity of radio-sensitizing gold nanoparticle (AACR 2024) - "Collectively, the results from in vitro study with PDAC cells confirm that the nanoconjugate with AMD070 enhances radio-cytotoxicity and impair CXCL12-CXCR4 downstream signaling. Hence AMD-PEG-GNP has strong merit to enhance radiation dose locally and simultaneously restrict RT induced immunosuppression in PDAC."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CAFs • CCR4 • CXCL12

Oral CXCR4 inhibition with mavorixafor: Emerging therapeutic applications in WHIM syndrome, chronic neutropenia, oncology, and stem cell mobilization. (PubMed, Curr Res Transl Med) - "Furthermore, this review positions mavorixafor within the broader CXCR4-targeted therapeutic landscape, identifying current research gaps and suggesting directions for future studies. In conclusion, by integrating mechanistic insights with preclinical and clinical findings, this article highlights mavorixafor's promise as a targeted therapy with the potential to transform treatment paradigms for CXCR4-driven diseases."

Journal • Review • Dermatology • Hematological Disorders • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Oncology • Waldenstrom Macroglobulinemia • CXCL12 • CXCR4

C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions. (PubMed, Cancer Pathog Ther) - "Antagonistic peptides AMD3100 (Plerixafor), LY2510924, and POL6326, as well as their therapeutic potential. Future research on Mavorixafor will focus on two main areas: personalized medicine development, new delivery systems and their broad medical applications extending beyond oncology. As a potential CXCR4 antagonist, Mavorixafor shows promise as a transformative tool in cancer care because it regulates the tumor microenvironment (TME) while increasing the degree of therapeutic benefits."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CXCL12 • CXCR4

On 26 February 2026, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation under exceptional circumstances for the medicinal product Xolremdi, intended for the treatment of WHIM syndrome (warts, hypogammaglobulinaemia, infections and myelokathexis) in adults and adolescents from 12 years of age. (European Medicines Agency)

CHMP • Rare Diseases

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

WHIM syndrome: from mechanism to targeted therapy - advances shaping clinical care. (PubMed, Curr Opin Allergy Clin Immunol) - "Increased awareness, opportunities for screening at birth, improved pathological and genetic diagnostics, and 2024 FDA approval of the first oral CXCR4 antagonist create practical advance in targeting WHIM syndrome. As a CID with lifetime risk for humoral deficiency, impaired antiviral defense and malignancy, WHIM warrants long-term monitoring and further investigation into broader applications of CXCR4 antagonism."

Journal • Review • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Oncology • Pediatrics • Primary Immunodeficiency

CXCR4 antagonism corrects neutrophil abnormalities and reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia. (PubMed, Front Immunol) - "Mavorixafor, an orally bioavailable CXCR4 antagonist, has shown meaningful increases in absolute neutrophil count and reduced infections in WHIM syndrome patients...Mice received the CXCR2 antagonist navarixin orally and then the CXCR4 antagonist compound 1 or vehicle control daily for 7 days...Our findings provide evidence that oral administration of a CXCR4 antagonist can effectively correct blood and BM neutrophil abnormalities and reduce infection susceptibility in a CXCR2 LOF mouse model. These findings suggest potential therapeutic benefits of CXCR4 antagonist therapy in addressing peripheral blood neutropenia and other pathogenic phenotypes in patients with CXCR2 LOF variants."

Journal • Preclinical • Dermatology • Hematological Disorders • Infectious Disease • Neutropenia • Pneumococcal Infections • Pneumonia • Respiratory Diseases • CXCR2

Trial in progress: A pivotal Phase 3 study to investigate efficacy, safety, and tolerability of mavorixafor in participants with primary chronic neutropenia – trial update (ASH 2025) - P3 | "This pivotal study, evaluating the efficacy, safety, and tolerability of mavorixafor in participants with CN experiencing recurrent and/or serious infections, is expected to support the registration of mavorixafor, alone or in combination with G-CSF, for the treatment of primary chronic neutropenia.This trial (NCT06056297), initiated in 2024, has close to 100 study centers activated and continues to enroll participants with 1 of 3 primary CN types (congenital, acquired idiopathic, and acquired autoimmune), including those who have been inadequately controlled (ANC <1000 cells/µL) while on a stable G-CSF regimen from baseline. Multiple sites are recruiting; many are accepting patient referrals."

Clinical • P3 data • Aplastic Anemia • Dermatology • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lupus Nephritis • Musculoskeletal Pain • Myelodysplastic Syndrome • Nephrology • Neutropenia • Osteoporosis • Rheumatology • Thrombocytopenia • Vasculitis

Role of genetic testing in diagnosing patients with severe congenital neutropenia: Results from PATH4WARD genetic testing program (ASH 2025) - P1/2 | "In 2022, at age 11 years, the male patient was found to harbor CXCR2 c.865C>T,p.Arg289Cys, a variant associated with SCN due to CXCR2 deficiency.1 In 2023 the patient was enrolled ina Phase 1b and Phase 2 clinical trial investigating mavorixafor in participants with congenital neutropeniaand chronic neutropenia disorders, including chronic idiopathic neutropenia (NCT04154488)...Despite this substantial reduction in G-CSF, the patient'sabsolute neutrophil count remained at or above approximately 1000 cells/µL throughout the study. Thiscase highlights the value of genetic testing in establishing a molecular diagnosis and enabling access toinvestigational agents through clinical trial participation, with the potential to improve clinical outcomes."

Clinical • Hematological Disorders • Immunology • Neutropenia • Primary Immunodeficiency • CD40LG • CSF3R • CXCR2 • CXCR4 • ELANE • GATA2 • TCIRG1

EMU-116: An oral CXCR4 antagonist as mobilizer of stem and immune cells in normal, neutropenic and sickle cell mice. (ASH 2025) - "The use of CXCR4 antagonists as cell mobilization agents has resulted in 3 FDA approved drugs for use inhematopoietic stem cell transplantation (Plerixafor, Motixafortide) and for treating neutropenia(Mavorixafor). In Swiss mice, EMU-116 dosed orally providesenhanced responses to cyclophosphamide indicating a potential use in chemotherapy-inducedneutropenia. In sickle cell mice, EMU-116 boosts LSKs when dosed orally and could possibly be utilizedfor a future in vivo gene therapy setting with superior effects to Plerixafor."

Immune cell • Preclinical • Bone Marrow Transplantation • Chemotherapy-Induced Neutropenia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease

CXCR4 antagonism reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia. (ASH 2025) - "Mavorixafor, an oralCXCR4 antagonist, has demonstrated a clinical benefit that includes increased neutrophil count andconcomitant reductions in infections for WHIM patients5...The current study aims to address these criticalquestions.MethodsFemale BALB/c mice (10-15 per group) were administered the CXCR2 antagonist navarixin (3 mg/kg) viaoral gavage, followed by daily doses of the CXCR4 antagonist X4P-002 (10 mg/kg) or a vehicle control for 4or up to 14 days, administered two hours after the navarixin dose...Notably, CXCR4 antagonism reduces the severity of pneumonia,likely associated with the normalization of neutrophil counts in infected tissues. In conjunction with ourprevious findings6, which showed that CXCR4 antagonism corrected blood and BM neutrophilabnormalities as well as reduced BM myelokathexis frequency, our data provide strong support forCXCR4 antagonist therapy as a promising treatment strategy for patients with CXCR2 LOF."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • CXCR2

Mavorixafor for Patients with Chronic Neutropenic Disorders Treated with G-CSF: Preliminary Response Data and G-CSF Dose Reduction in an Ongoing Phase 2, Open-Label, Multicenter Study Support Reduction in G-CSF Dosing (ASH 2023) - P1/2, P3 | "Our report shows that chronic treatment with oral, once-daily mavorixafor in combination with G-CSF resulted in durable increases in ANC compared with BL for ≥3 months in 3 study participants. Reduction of injectable G-CSF dosing was implemented in 2 study participants with CIN following robust ANC increase observed after the first 2 months of combination treatment. These preliminary data also support the safety of concomitant treatment with G-CSF and mavorixafor."

Clinical • P2 data • Dermatology • Hematological Disorders • Infectious Disease • Neutropenia • ELANE

A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections (clinicaltrials.gov) - P3 | N=176 | Recruiting | Sponsor: X4 Pharmaceuticals | Trial completion date: Aug 2026 ➔ Nov 2027 | Trial primary completion date: Jul 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Immunology • Infectious Disease • Neutropenia

Mavorixafor, a Novel CXC4 Agonist for WHIM Syndrome: Challenges in Successful Drug Development in Rare Hematologic Disorders (ASH 2024) - No abstract available

Hematological Disorders