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

Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome (clinicaltrials.gov) - P3 | N=31 | Active, not recruiting | Sponsor: X4 Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Dermatology • Infectious Disease • CXCR4

Drug-Drug Interaction Potential of Mavorixafor (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: X4 Pharmaceuticals | Recruiting ➔ Completed

Trial completion

EVALUATING THE SAFETY AND EFFICACY OF MAVORIXAFOR, AN ORAL CXCR4 ANTAGONIST, IN PATIENTS WITH CHRONIC NEUTROPENIC DISORDERS: RESULTS FROM THE PHASE 2 STUDY (EHA 2025) - "Treatment with mavorixafor, alone or with stable dosage or dosage-adjusted G-CSF, was generally well tolerated and meaningfully and durably increased ANC levels in participants with CN regardless of subtype."

Clinical • P2 data • Hematological Disorders • Infectious Disease • Neutropenia • ELANE • SRP54

MAVORIXAFOR, AN ORAL CXCR4 ANTAGONIST, ALLOWS FOR GRANULOCYTE-COLONY STIMULATING FACTOR DOSE DE-ESCALATION IN PATIENTS WITH CHRONIC IDIOPATHIC NEUTROPENIA AND CONGENITAL NEUTROPENIA (EHA 2025) - "The majority of participants and investigators were willing to substantially reduce or discontinue G-CSF use with mavorixafor treatment. All participants with congenial neutropenia concurrently treated with G-CSF, including one with ELANE, were able to decrease G-CSF while maintaining normal mean ANC levels. This study provides the first evidence that a significant subset of patients with CIN may be able to successfully transition off G-CSF to mavorixafor, providing an oral option to treat chronic neutropenia."

Hematological Disorders • Infectious Disease • Neutropenia • ELANE

CXCR4-R334X MOUSE: A MODEL TO INVESTIGATE THE PATHOGENESIS OF WHIM SYNDROME AND ASSESS NOVEL GENE CORRECTION THERAPY (EHA 2025) - "Treatment is conservative with immunoglobulin supplementation, administration of recombinant G-CSF, low-dose Plerixafor/Mavorixafor, HPV vaccination; haematopoietic stem cell transplantation (HSCT) has anecdotally reported to be curative. These preliminary results show that murine HSPC are highly permissive to mRNA delivery by LNPs transfection, ex vivo. Next, we will apply this protocol to HSPC isolated from WHIM mice for gene correction of Cxcr4-R334X mutation by testing ABE-machinery and ultimately prove the efficacy of this approach in the preclinical disease model."

Preclinical • Bone Marrow Transplantation • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Neutropenia • Primary Immunodeficiency • CXCR4

X4 Pharmaceuticals Presents Positive Phase 2 Chronic Neutropenia Trial Data in Poster Presentations at the 30th Annual Congress of the European Hematology Association (EHA) (GlobeNewswire) - P1b/2 | N=32 | NCT04154488 | Sponsor: X4 Pharmaceuticals | "Results from participants receiving oral, once-daily mavorixafor monotherapy showed that mavorixafor durably increased mean ANC from baseline over the 6-month trial. Further analysis showed that those with severe CN achieved nearly 3-fold increases in mean ANC levels out to six months, reaching levels typically targeted by physicians for patients with severe chronic neutropenia; In addition, a sub-study comparing the mean percentage of functional neutrophils in samples from healthy donors (n=5) to participants from the Phase 2 CN study (n=9) showed that the mean percentage of functional circulating neutrophils in CN participants in this sub-study was comparable to that of healthy donors after six months of mavorixafor dosing; Mavorixafor was generally well tolerated as monotherapy and in combination with injectable G-CSF during the trial."

P2 data • Neutropenia

X4 Pharmaceuticals Granted Fast Track Designation for Mavorixafor for the Treatment of Chronic Neutropenia by U.S. FDA (GlobeNewswire) - "X4 Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to mavorixafor, an oral CXCR4 antagonist, for the treatment of chronic neutropenia (CN). The company is currently conducting a global, pivotal Phase 3 clinical trial (4WARD) evaluating mavorixafor in certain primary CN conditions....'With enrollment ongoing in our Phase 3 4WARD trial of mavorixafor in CN, we continue to expect full enrollment in the third or fourth quarter of this year and potential top-line data in late 2026'."

Enrollment status • Fast track • P3 data: top line • Neutropenia

Synthesis and 64Cu-Radiolabeling Strategies of Small Organic Radioconjugates Based on the AMD070 Scaffold. (PubMed, ChemMedChem) - "These are based mainly on nitrogen-rich scaffolds, such as AMD070, and cyclic polyamines such as cyclam in the AMD3100 skeleton. Herein, we describe the synthesis of two novel CXCR4-directed radiopharmaceuticals, combining the AMD070 scaffold as a targeting unit, and bifunctional te1pa macrocycle as a strong 64Cu chelator. The synthesis of the conjugates and optimization of 64Cu-radiolabeling are presented, opening the way for future in vitro and in vivo studies."

Journal • Oncology • CXCR4

WHIM Syndrome Diagnosis in a Parent and Child (CIS 2025) - "Mavorixafor was started and pegfilgrastim discontinued with no sinopulmonary infections or hospitalizations since initiation. However, skin rashes worsened, and he developed an axillary abscess requiring trimethoprim-sulfamethoxazole and cephalexin therapy...PIDs with milder phenotypes are often not considered in adult patients until severe manifestations occur, as seen in Case 1. Diagnosis of PIDs should prompt early immune evaluation with consideration of genetic testing in family members."

Clinical • Dermatology • Immunology • Infectious Disease • Otorhinolaryngology • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • Tetanus • CD4 • CD8 • CXCR4

Clinical Response Among Participants with Warts in the Phase 3 Trial, Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome (CIS 2025) - P3 | "Plerixafor, an injectable CXCR4 antagonist, has shown improvement in warts in WHIM syndrome; however, the question remains whether CXCR4 antagonism shows a wart benefit in this population. Two-year treatment with chronic oral mavorixafor was associated with marked clinical improvement in wart severity, providing further evidence that CXCR4 antagonism leads to wart improvement in patients with WHIM syndrome."

Clinical • P3 data • Dermatology • Immunology • Infectious Disease • Primary Immunodeficiency

Mavorixafor Inhibits Pathogenic Cxcr4 Signaling and Function in T Lymphocytes from Patients with WHIM Syndrome in vitro (CIS 2025) - P3 | "This study represents the first comprehensive characterization of CXCR4 GOF phenotypes in T lymphocytes from a large cohort of individuals with WHIM syndrome. The correction of underlying molecular defects may be linked to improved leukocyte mobilization observed in participants in the mavorixafor WHIM syndrome phase 3 trial."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Primary Immunodeficiency • CXCL12

Norgine strengthens rare disease portfolio with acquisition of Theravia (PRNewswire) - "Norgine and Theravia announced today that they have entered into a definitive agreement under which Norgine will acquire Theravia, an international pharmaceutical company specialising in cutting-edge treatments for patients with rare and debilitating conditions....With the acquisition of Theravia, Norgine will now have...core products in its rare disease portfolio (PEDMARQSI, eflornithine, mavorixafor, SIKLOS) thereby comprising a franchise of critical scale with the ability to be a key growth driver in the medium-to-long-term."

M&A • Dermatology • Genetic Disorders • Hematological Disorders • Otorhinolaryngology

Mavorixafor: a CXCR4 antagonist for WHIM syndrome. (PubMed, Immunopharmacol Immunotoxicol) - "Mavorixafor 400mg daily effectively increases WBC count, reduces disease symptoms and infection burden in WHIM syndrome patients ≥12 years. Future clinical programs will continue to evaluate the safety and efficacy of mavorixafor in patients with chronic neutropenic disease."

Journal • Review • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Neutropenia • Primary Immunodeficiency • Thrombocytopenia • CXCL12

Mavorixafor, CXCR4 antagonist, a novel treatment for WHIM syndrome, first FDA approval 2024. (PubMed, Ann Med Surg (Lond)) - "Traditionally, WHIM syndrome has been managed with intravenous immunoglobulin (IVIG) and filgrastim (granulocyte colony-stimulating factor). These findings underscore the potential of Mavorixafor to significantly improve clinical outcomes for patients with WHIM syndrome, offering a more effective and targeted treatment option. The approval of Mavorixafor not only enhances current therapeutic strategies but also paves the way for future research into CXCR4 antagonists, potentially revolutionizing the management of WHIM syndrome and similar immunodeficiencies."

FDA event • Journal • Dermatology • Hematological Disorders • Infectious Disease • Neutropenia

Drug-Drug Interaction Potential of Mavorixafor (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: X4 Pharmaceuticals

New P1 trial

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=48 | Recruiting | Sponsor: X4 Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis C • Hepatology • Liver Failure

Unveiling WHIM syndrome: Mavorixafor's Emerging Role in Immune Restoration and Therapy. (PubMed, Clin Exp Immunol) - "The review also aims to thoroughly assess the efficacy and safety of Mavorixafor in managing WHIM syndrome, exploring its pharmacokinetics, pharmacodynamics, dosing regimens, and safety. Finally, we also investigate important additional therapeutic uses of Mavorixafor."

Journal • Bone Marrow Transplantation • Dermatology • Infectious Disease • Transplantation

Structural mechanisms underlying the modulation of CXCR4 by diverse small-molecule antagonists. (PubMed, Proc Natl Acad Sci U S A) - "To date, only two small-molecule antagonist drugs targeting CXCR4, plerixafor (AMD3100) and mavorixafor (AMD070), have been approved. Both the major and minor subpockets on CXCR4 are found to be involved in binding of these small-molecule antagonists. The distinct conformations of Trp942.60 observed in these structures highlight the plasticity of the binding pocket on CXCR4, offering valuable insights into the exploration and refinement of therapeutic strategies targeting this chemokine receptor."

Journal • Human Immunodeficiency Virus • Infectious Disease • CXCR4

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=48 | Not yet recruiting | Sponsor: X4 Pharmaceuticals

New P1 trial • Hepatitis C • Hepatology • Liver Failure

X4 Pharmaceuticals and taiba rare Announce Exclusive Agreement for the Distribution and Commercialization of XOLREMDI (mavorixafor) in WHIM Syndrome in Select Middle East Countries (GlobeNewswire) - "X4 Pharmaceuticals...today announced that they have entered into an exclusive agreement for the distribution and commercialization of XOLREMDI (mavorixafor), an oral, once-daily treatment for WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis), in select Middle East countries (Saudi Arabia, United Arab Emirates, Qatar, Oman, Kuwait, Bahrain, and Egypt), following any approvals in the region."

Commercial • Genetic Disorders • Immunology • Primary Immunodeficiency

Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024. (PubMed, Expert Opin Ther Pat) - "Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved. In the last five years there has been significant advancement in CXCR4 antagonists as gauged by the FDA approval of two drugs. The search for second and third generation compounds will be the focus of future efforts with new uses and better properties which likely could come from some of the IP described herein."

Journal • Review • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology

X4 Pharmaceuticals Announces EMA Validation of Marketing Authorization Application (MAA) for Mavorixafor for the Treatment of WHIM Syndrome (GlobeNewswire) - "Submission supported by positive results from global, Phase 3 4WHIM clinical trial...Decision on MAA expected in 1H 2026...X4 Pharmaceuticals...today announced that its Marketing Authorization Application (MAA) for mavorixafor for the treatment of WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis), a rare primary immunodeficiency, has been validated for review and is now under evaluation with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP)."

EMA approval • EMA filing • Primary Immunodeficiency • Rare Diseases

CXCR4 Antagonism Corrects Peripheral Neutropenia and Mature Neutrophil Accumulation in Bone Marrow in a Pharmacological Mouse Model of CXCR2 Loss-of-Function (ASH 2024) - "Additional clinical manifestations in patients with WHIM syndrome may include warts, hypogammaglobulinemia and lymphocytopenia.1,2 Interestingly, patients with loss-of-function (LoF) variants in CXCR2 display phenotypic features similar to those observed in patients with WHIM syndrome, such as neutropenia, increased infection susceptibility, and myelokathexis.3,4 Mavorixafor, an orally bioavailable CXCR4 antagonist, has demonstrated clinically meaningful increases in absolute neutrophil and lymphocyte counts and concomitant reductions in infections in patients aged 12 years and older with WHIM syndrome, leading to its recent approval by the U.S. Food and Drug Administration.5 Whether CXCR4 antagonist therapy can similarly correct the common pathogenic phenotypes observed in patients with CXCR2 LoF variants as are seen in patients with WHIM syndrome has yet to be determined...Methods Female BALB/c mice (6 mice per group) were dosed with the CXCR2 antagonist navarixin (3..."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Primary Immunodeficiency • CXCR2

Dual Inhibition of CXCR4 and Claudin-18 Isoform X1 in Gastric Adenocarcinoma: An in Silico Study (IGICC 2024) - "This study represents a comprehensive in silico investigation into the simultaneous targeting of CXCR4 and Claudin-18 isoform X1. The data obtained underscore the potential of multimodal targeting strategies in the treatment of gastric adenocarcinoma and demonstrate the efficacy of in silico methods in rational drug design processes. The identification of Burixafor and Mavorixafor as dual-targeted agents establishes a robust molecular foundation for preclinical and clinical studies."

Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • CXCR4

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

Hematological Disorders