Motixafortide

BL-8040, BKT140, 4F-benzoyl-TN14003, Aphexda

Oncology & imaging

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Motixafortide is an approved prescription medicine used in hospital, under specialist supervision, to mobilise stem cells before autologous transplant in multiple myeloma. This page explains the published science. Community or self-directed use is essentially none documented.

Summary

Class: Synthetic 14-amino-acid cyclic peptide (disulfide-bridged) containing non-natural residues, derived from the T140 series of CXCR4 antagonists; a high-affinity, long-acting CXCR4 inhibitor
Mechanism: Blocks the CXCR4 receptor on haematopoietic stem cells, breaking the CXCL12 (SDF-1) "anchor" that holds them in the bone marrow so they spill into the blood where they can be collected
Routes studied: Subcutaneous injection (approved); also intravenous and in combination with chemotherapy and checkpoint inhibitors in cancer trials
Half-life: Approximately 2 hours in plasma, but receptor occupancy and mobilisation effect persist for at least 24–48 hours because of very slow dissociation from CXCR4
Storage: Lyophilised powder in single-dose vials, refrigerated; reconstituted in hospital pharmacy and used within hours
Regulatory status: Approved medicine (US 2023); EU application status †

Doses are as reported in studies or by the community — never recommendations.

1What it is

Motixafortide comes from a line of peptides first developed in Japan as anti-HIV agents (T22 and T140), because CXCR4 is a co-receptor the virus uses to enter cells. CXCR4 turned out to matter far more for a different reason: together with its partner chemokine CXCL12, it keeps blood-forming stem cells anchored in bone-marrow niches. Blocking it releases them. The first drug to exploit this, plerixafor, is a small molecule approved in 2008. Motixafortide binds CXCR4 far more tightly and for longer, which produces a bigger and more sustained release of stem cells from a single injection.

In autologous stem-cell transplant for multiple myeloma, the patient's own stem cells must be collected in sufficient numbers before high-dose chemotherapy. Many patients, especially after lenalidomide-containing induction, do not mobilise enough cells with G-CSF alone and need multiple days of apheresis. Motixafortide was approved by the FDA in September 2023 for use with filgrastim in this setting.

2How it's thought to work

CXCL12 produced by marrow stromal cells binds CXCR4 on stem cells and holds them in the niche. Motixafortide occupies CXCR4 with sub-nanomolar affinity and dissociates very slowly (hours), so the anchor stays broken long after plasma drug has cleared.

Combined with four days of G-CSF (which also reduces CXCL12 and loosens the niche), a single dose produces a peak of circulating CD34+ cells in 10–14 hours that is many times higher than with G-CSF alone.

In cancer biology, CXCR4 also drives tumour homing, metastasis and immune exclusion; blocking it is being tested to let T cells into pancreatic tumours. This is a separate, investigational use.

A CXCR4 antagonist. The receptor is what anchors haematopoietic stem cells in the marrow; blocking it releases them into the blood, where they can be collected for transplant.Schematic — not to scale

3What the research shows

Stem-cell mobilisation in multiple myeloma

GENESIS randomised 122 patients to motixafortide or placebo on top of G-CSF. The primary endpoint (collecting at least 6 million CD34+ cells/kg in up to two apheresis sessions) was met by 92.5% with motixafortide versus 26.2% with placebo; 88.8% versus 9.5% reached that target in a single session. Grafts contained more primitive stem cells and engraftment was durable (Crees 2023, Nat Med). Compared with historical plerixafor data, the single-session collection rate appears higher, but no head-to-head randomised comparison exists. [1]

Mobilisation for gene therapy and sickle-cell disease

Small studies have explored motixafortide alone or with natalizumab to collect stem cells from people with sickle-cell disease, where G-CSF is contraindicated; early results reported adequate yields in a handful of patients †.

Pancreatic cancer (with checkpoint inhibitor and chemotherapy)

COMBAT, a Phase 2a single-arm study combining motixafortide with pembrolizumab and chemotherapy in second-line metastatic pancreatic cancer, reported response rates and survival that compared favourably with historical controls (Bockorny 2020, Nat Med). A randomised Phase 2 in first-line disease is ongoing †. [2]

Acute myeloid leukaemia (chemosensitisation)

Phase 2 work combining BL-8040 with cytarabine or with atezolizumab in relapsed AML showed mobilisation of leukaemic blasts and some responses; not advanced to Phase 3 †.

4Reported side effects and interactions

Literature-reported

Injection-site reactions were near-universal in GENESIS (around 73%, including pain, erythema and pruritus), along with flushing, pruritus and back pain; most were transient and resolved within hours. Anaphylactic reactions were reported, and the label requires pre-medication with an antihistamine, an H2 blocker and an anti-emetic and observation for an hour after injection. Hypoxia and hypotension can occur acutely. Theoretical risks shared with plerixafor: mobilisation of tumour cells into the graft (not seen as a clinical problem in myeloma), leukocytosis, and splenic enlargement with rupture (reported with G-CSF).

Community-reported

none documented.

Theoretical. CXCR4 blockade affects immune-cell trafficking; effects with prolonged dosing (as in the oncology trials) are not fully characterised.

Interactions. none pharmacokinetic. Co-administration with G-CSF is the intended use and is additive. Should not be given to patients with leukaemia for autologous collection (risk of mobilising malignant cells).

Markers researchers commonly monitor

Per label and transplant practice:

Marker	Why it's watched
Peripheral blood CD34+ cell count	measured on the morning of apheresis to decide whether and how long to collect; the central efficacy marker.
White blood cell count	rises sharply with G-CSF plus motixafortide; very high counts are a reason to delay.
Platelet count	apheresis lowers platelets; checked before each session.
Vital signs and oxygen saturation for one hour after injection	because of the anaphylaxis and hypoxia warnings.
Post-transplant neutrophil and platelet engraftment days	the downstream measure of graft quality.
Spleen size	if left-upper-quadrant pain occurs during mobilisation.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Hospital-pharmacy product. Each vial contains 62 mg of motixafortide, with 0.9% sodium chloride to 62 mg/mL; the weight-based dose is drawn up and injected subcutaneously into the abdomen, with pre-medication given 30–60 minutes before. Doses above 2 mL are split between sites. The calculator does not apply.

6Commonly studied alongside

Filgrastim (G-CSF) as the required partner; plerixafor as the comparator class member (a non-peptide); pembrolizumab and chemotherapy in pancreatic cancer; natalizumab in sickle-cell mobilisation. Related CXCR4-targeted peptides on this site: peptide radiotracers such as pentixafor (a CXCR4 PET agent) if covered in the imaging batch.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved September 2023 (Aphexda) in combination with filgrastim to mobilise haematopoietic stem cells for collection and autologous transplant in multiple myeloma
European Union	Not authorised; marketing authorisation application status †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport (WADA)	Not specifically listed; stem-cell mobilising agents are not a performance-enhancing class, but any use outside approved indications is S0. Check current list †

8Open questions

Head-to-head efficacy, cost-effectiveness and graft quality versus plerixafor; only historical comparisons exist.
Whether CXCR4 blockade improves immunotherapy outcomes in pancreatic or other "cold" tumours in randomised trials.
Use in allogeneic donors and in non-malignant conditions such as sickle-cell gene therapy.

9References

1Crees ZD et al. (2023). Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial (GENESIS). Nat Med. PubMed · DOI
2Bockorny B et al. (2020). BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. PubMed · DOI
3Peled A et al. (2014). The high-affinity CXCR4 antagonist BKT140 is safe and induces a robust mobilization of human CD34+ cells in patients with multiple myeloma. Clin Cancer Res. PubMed · DOI
4Tamamura H et al. (2003). Enhancement of the T140-based pharmacophores leads to the development of more potent and bio-stable CXCR4 antagonists. Org Biomol Chem [verify]. PubMed · DOI
5Abraham M et al. (2017). Single dose of the CXCR4 antagonist BL-8040 induces rapid mobilization for the collection of human CD34+ cells in healthy volunteers. Clin Cancer Res. PubMed · DOI
6Aphexda US prescribing information (2023); FDA Drug Trials Snapshot: Aphexda. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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