Mavorixafor

Last updated

Mavorixafor
Mavorixafor.svg
Clinical data
Trade names Xolremdi
Other namesX4P-001; AMD-070
License data
Routes of
administration
By mouth
Drug class CXCR4 antagonist
ATC code
  • None
Legal status
Legal status
Identifiers
  • N-(1H-Benzimidazol-2-ylmethyl)-N-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H27N5
Molar mass 349.482 g·mol−1
3D model (JSmol)
  • C1C[C@@H](C2=C(C1)C=CC=N2)N(CCCCN)CC3=NC4=CC=CC=C4N3
  • InChI=1S/C21H27N5/c22-12-3-4-14-26(15-20-24-17-9-1-2-10-18(17)25-20)19-11-5-7-16-8-6-13-23-21(16)19/h1-2,6,8-10,13,19H,3-5,7,11-12,14-15,22H2,(H,24,25)/t19-/m0/s1
  • Key:WVLHHLRVNDMIAR-IBGZPJMESA-N

Mavorixafor, sold under the brand name Xolremdi, is a medication used for the treatment of WHIM syndrome. [1] It is a CXC chemokine receptor 4 antagonist. [1] It is taken by mouth. [1] It was developed by X4 Pharmaceuticals.

Contents

The most frequently reported adverse reactions include thrombocytopenia (low platelet counts), rash, rhinitis (stuffy nose), epistaxis (nosebleed), vomiting, and dizziness. [2]

Mavorixafor was approved for medical use in the United States in April 2024. [1] [2] [3] [4]

Medical uses

Mavorixafor is indicated in people twelve years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes. [1] [2]

Adverse effects

Mavorixafor is expected to cause harm to the baby. [1] [2]

History

The effectiveness of mavorixafor was evaluated in a 52-week, randomized, double-blind, placebo-controlled trial that enrolled 31 adolescents and adults with WHIM syndrome (NCT03995108). [2] Mavorixafor improved absolute neutrophil counts and absolute lymphocyte counts, assessed over a 24-hour period four times throughout the study. [2] Absolute neutrophil counts below 500 cells/µL and absolute lymphocyte counts below 1000 cells/µL are associated with an increased risk of infections. [2] The average length of time over 24 hours that counts were above these levels was significantly longer with mavorixafor compared to the placebo group (15.0 hours compared to 2.8 hours for absolute neutrophil counts; 15.8 hours compared to 4.6 hours for absolute lymphocyte counts). [2]

Society and culture

Names

Mavorixafor is the international nonproprietary name. [5]

Research

Mavorixafor is in clinical trials for melanoma [6] and renal cell carcinoma. [7]

Related Research Articles

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

Myelokathexis is a congenital disorder of the white blood cells that causes severe, chronic leukopenia and neutropenia. The disorder is believed to be inherited in an autosomal dominant manner. Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). The disorder shows prominent neutrophil morphologic abnormalities.

<span class="mw-page-title-main">CXCR4</span> Protein

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene. The protein is a CXC chemokine receptor.

Hypogammaglobulinemia is an immune system disorder in which not enough gamma globulins are produced in the blood. This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as medication, blood cancer, or poor nutrition, or loss of gamma globulins in urine, as in nonselective glomerular proteinuria. Patients with hypogammaglobulinemia have reduced immune function; important considerations include avoiding use of live vaccines, and take precautionary measures when traveling to regions with endemic disease or poor sanitation such as receiving immunizations, taking antibiotics abroad, drinking only safe or boiled water, arranging appropriate medical cover in advance of travel, and ensuring continuation of any immunoglobulin infusions needed.

<span class="mw-page-title-main">Sorafenib</span> Chemical compound

Sorafenib, sold under the brand name Nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer, advanced primary liver cancer, FLT3-ITD positive AML and radioactive iodine resistant advanced thyroid carcinoma.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">WHIM syndrome</span> Medical condition

WHIM syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia.

<span class="mw-page-title-main">Ibrutinib</span> Medication used in cancer treatment

Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia. Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

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Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

A CXCR4 antagonist is a substance which blocks the CXCR4 receptor and prevent its activation. Blocking the receptor stops the receptor's ligand, CXCL12, from binding which prevents downstream effects. CXCR4 antagonists are especially important for hindering cancer progression because one of the downstream effects initiated by CXCR4 receptor activation is cell movement which helps the spread of cancer, known as metastasis. The CXCR4 receptor has been targeted by antagonistic substances since being identified as a co-receptor in HIV and assisting the development of cancer. Macrocyclic ligands have been utilised as CXCR4 antagonists.

Inebilizumab, sold under the brand name Uplizna, is a medication for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults. Inebilizumab is a humanized mAb that binds to and depletes CD19+ B cells including plasmablasts and plasma cells.

<span class="mw-page-title-main">Tislelizumab</span> Monoclonal antibody

Tislelizumab, sold under the brand name Tevimbra among others, is a humanized monoclonal antibody directed against programmed death receptor-1. It is being developed by BeiGene.

Relatlimab is a monoclonal antibody designed for the treatment of melanoma. It is used in combination with nivolumab to treat melanoma.

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<span class="mw-page-title-main">Avacopan</span> Chemical compound

Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Avacopan is a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor.

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<span class="mw-page-title-main">Leniolisib</span> Medication

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References

  1. 1 2 3 4 5 6 7 "Xolremdi (mavorixafor) capsules, for oral use" (PDF). Archived (PDF) from the original on 30 April 2024. Retrieved 29 April 2024.
  2. 1 2 3 4 5 6 7 8 "FDA approves first drug for WHIM syndrome, a rare disorder". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 29 April 2024. Retrieved 29 April 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
  4. "X4 Pharmaceuticals Announces FDA Approval of Xolremdi (mavorixafor) Capsules, First Drug Indicated in Patients with WHIM Syndrome" (Press release). X4 Pharmaceuticals. 29 April 2024. Archived from the original on 29 April 2024. Retrieved 29 April 2024 via GlobeNewswire.
  5. World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl: 10665/330907 .
  6. Andtbacka, Robert H.I.; Wang, Yan; Pierce, Robert H.; Campbell, Jean S.; Yushak, Melinda; Milhem, Mohammed; et al. (31 August 2022). "Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma". Cancer Research Communications. 2 (8): 904–913. doi: 10.1158/2767-9764.CRC-22-0090 . PMC   10010370 . PMID   36923305.
  7. Choueiri, Toni K.; Atkins, Michael B.; Rose, Tracy L.; Alter, Robert S.; Ju, Yawen; Niland, Katie; et al. (August 2021). "A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced renal cell carcinoma patients with no prior response to nivolumab monotherapy". Investigational New Drugs. 39 (4): 1019–1027. doi:10.1007/s10637-020-01058-2. PMID   33507454. S2CID   231746027.