Motixafortide

A synthetic 14-residue cyclic peptide CXCR4 antagonist, FDA approved since 2023 as Aphexda, given with filgrastim to mobilize hematopoietic stem cells into the blood for collection before autologous transplant in multiple myeloma.

Also referenced as: Motixafortide acetate, Aphexda, BL-8040, BL8040, BKT140, BKT-140, TN14003, 4F-benzoyl-TN14003, 4-fluorobenzoyl-TN14003

Also appears in: Other

COA Public product evidence No certificate records are bound to a tracked Motixafortide product page A record counts here only when a vendor publishes a certificate against one of its own tracked Motixafortide product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is Motixafortide?

Motixafortide is a synthetic 14-amino-acid cyclic peptide that blocks the chemokine receptor CXCR4. It descends from T140, a polyphemusin-derived peptide originally studied as an HIV entry inhibitor, and carries a 4-fluorobenzoyl group on its N-terminus and a disulfide bridge between residues 4 and 13 that holds the chain in a short antiparallel beta-sheet; the free base has a molecular weight of about 2,160 g/mol (C97H144FN33O19S2). It was known in the literature as 4F-benzoyl-TN14003, then BKT140 (Biokine Therapeutics), then BL-8040 (BioLineRx, which licensed it from Biokine), before receiving the nonproprietary name motixafortide.

The FDA approved it on September 8, 2023 under the brand name Aphexda, in combination with filgrastim (G-CSF), to mobilize hematopoietic stem cells into the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. It is a hospital drug given once or twice by a transplant team in the days before apheresis. It appears in the research-peptide market mainly as a reagent-grade CXCR4 antagonist, listed under its development codes, because of its well-characterized receptor pharmacology rather than any self-administration use case.

How it works

CXCR4 and its ligand CXCL12 (SDF-1) form the main retention signal that keeps hematopoietic stem and progenitor cells anchored in the bone marrow niche. Blocking the receptor releases them into circulation, where they can be collected.

• High-affinity, long-residence CXCR4 antagonism — motixafortide binds CXCR4 with roughly 4 nmol/L affinity compared with about 84 nmol/L for the small-molecule antagonist plerixafor, and the label reports receptor occupancy maintained for more than 72 hours after a dose; in the first patient study a single subcutaneous dose given 12 hours before that day’s G-CSF was enough to drive collection of a full transplant dose in one apheresis at the top dose level (Peled et al., Clinical Cancer Research, 2014, 20(2):469–479)
• Engineered biostability — the N-terminal 4-fluorobenzoyl modification and the citrulline and D-amino-acid residues in the T140 scaffold were introduced to raise potency and resist serum and liver proteases, which is why this analog, rather than parent T140, advanced into the clinic (Tamamura et al., Organic & Biomolecular Chemistry, 2003, 1(21):3663–3669)
• Mobilizes a more primitive stem cell population — in the Phase 3 program, motixafortide plus G-CSF preferentially mobilized increased numbers of CD34+ cells that were immunophenotypically and transcriptionally more primitive than those mobilized by G-CSF alone, with engraftment kinetics and graft durability comparable between arms; the subset analysis was post hoc and the trial was not designed to tie subsets to clinical outcomes (Crees et al., Nature Medicine, 2023, 29(4):869–879)
• Direct and immunologic antitumor activity in models — unlike plerixafor, 4F-benzoyl-TN14003 (BKT140) showed CXCR4-dependent cytotoxicity toward myeloma and leukemia cells in vitro and slowed xenograft growth in vivo (Beider et al., Experimental Hematology, 2011, 39(3):282–292); in pancreatic tumors, CXCR4 blockade increased CD8+ effector T-cell infiltration and reduced myeloid-derived suppressor cells, the rationale for pairing it with PD-1 inhibitors (Bockorny et al., Nature Medicine, 2020, 26(6):878–885)

Research status

Motixafortide has one completed, positive Phase 3 trial supporting its approval, and a longer record of oncology studies with mixed outcomes.

GENESIS (NCT03246529). A Phase 3, double-blind, placebo-controlled study run at 18 sites in five countries, most patients in the United States. After an 11-patient open-label lead-in, Part 2 randomized 122 adults with multiple myeloma 2:1 to a single dose of motixafortide 1.25 mg/kg or placebo on the fourth day of G-CSF mobilization, with apheresis starting on day 5 and an optional second dose if needed. The primary endpoint, collection of at least 6 × 10^6 CD34+ cells/kg within two apheresis sessions, was met by 92.5% of the motixafortide arm versus 26.2% of placebo (odds ratio 53.3; P < 0.0001); 88.8% versus 9.5% reached that threshold in a single apheresis. The most common adverse events were transient grade 1–2 injection-site reactions: pain in 50%, erythema in 27.5%, and pruritus in 21.3% (Crees et al., Nature Medicine, 2023, 29(4):869–879). The FDA approval of September 8, 2023 rested on this trial. The Orange Book lists new-chemical-entity exclusivity through September 8, 2028 and orphan-drug exclusivity for the myeloma mobilization indication through September 8, 2030; the compound also holds orphan designations for pancreatic cancer (U.S. and EU) and acute myeloid leukemia (U.S.). The registry still lists GENESIS as active, not recruiting, for long-term follow-up with an estimated completion in 2029.

Earlier mobilization work. The first patient study gave single escalating doses of BKT140 (0.006 to 0.9 mg/kg) to 18 myeloma patients after cyclophosphamide and G-CSF; at the top dose a single apheresis collected a mean of 20.6 × 10^6 CD34+ cells/kg, no grade 3–4 toxicity occurred, and 17 patients engrafted promptly (Peled et al., Clinical Cancer Research, 2014, 20(2):469–479).

Acute myeloid leukemia — stalled. A Phase 2a open-label study combined BL-8040 with high-dose cytarabine in 42 patients with relapsed or refractory AML across six dose levels. The composite complete remission rate was 29% overall and 39% in the 23-patient 1.5 mg/kg expansion cohort, with a median overall survival of 8.4 months overall and 10.8 months at 1.5 mg/kg (Borthakur et al., Cancer, 2021, 127(8):1246–1259). The sponsor did not advance AML into a registrational trial, the indication is not on the approved label, and the label states the drug is not intended for mobilization in leukemia patients. A 10-patient investigator-initiated pilot (registered as Phase 2) of motixafortide for measurable-residual-disease sensitization in AML at Washington University (NCT07392970), with Gamida Cell as collaborator, started in July 2026 and is recruiting, with primary completion estimated in 2028.

Pancreatic cancer — still open. COMBAT/KEYNOTE-202 (NCT02826486), a Phase 2a open-label study in metastatic pancreatic ductal adenocarcinoma that enrolled 80 patients in all, reported 37 chemotherapy-resistant patients on BL-8040 plus pembrolizumab (disease control rate 34.5% in the 29-patient modified intention-to-treat set, one partial response, median overall survival 3.3 months) and 22 patients on the same pair plus liposomal irinotecan, fluorouracil and leucovorin (objective response rate 32%, disease control rate 77%, median duration of response 7.8 months) (Bockorny et al., Nature Medicine, 2020, 26(6):878–885). Those single-arm numbers are hypothesis-generating, not confirmatory. The follow-on CheMo4METPANC study (NCT04543071), led by Columbia University with cemiplimab, gemcitabine, and nab-paclitaxel in first-line metastatic disease, is listed in the registry as a single-arm Phase 2 with an estimated 118 patients and a 16-week objective-response primary endpoint; it is active and not recruiting as of its September 2026 update, with primary completion estimated for mid-2028. BioLineRx retained solid-tumor rights for this program.

Sickle cell disease — Phase 1. A Washington University pilot (NCT05618301) tested motixafortide alone and, after an eight-week washout, with natalizumab as a plerixafor alternative for collecting the very large CD34+ doses that gene therapies require. It enrolled 10 participants and completed in June 2025. At the December 2025 ASH annual meeting the licensee reported the regimen as safe and well tolerated, with predicted single-apheresis yields of 16.9 and 19.6 million cells/kg for motixafortide alone and with natalizumab, about 2.7- and 2.8-fold above plerixafor. These results exist as conference presentations and sponsor announcements; no peer-reviewed full publication was found as of November 2026. A second Phase 1 at St. Jude Children’s Research Hospital (NCT06442761, 20 patients planned, Ayrmid as collaborator) is recruiting with an estimated completion in 2028. At the February 2026 Tandem Meetings the licensee presented real-world data from five centers in which motixafortide mobilized enough cells for gene-therapy manufacturing in 11 of 15 sickle cell patients, most of whom had previously failed plerixafor, and described a G-CSF combination for beta-thalassemia.

Commercial history and current label. BioLineRx licensed Asian rights to Gloria Biosciences in August 2023, and Gloria started its own 60-patient randomized Phase 3 mobilization study in China (NCT06514508) in December 2025. BioLineRx brought the drug to the U.S. market itself after approval, then under an agreement dated November 20, 2024 (announced November 21) licensed it for all indications except solid tumors, in all territories outside Asia, to Ayrmid Ltd., the parent of Gamida Cell, for $10 million upfront, up to $87 million in commercial milestones and 18–23% royalties; Ayrmid said it would take on members of BioLineRx’s U.S. commercial team. The U.S. prescribing information was revised in October 2025 (FDA labeling supplement approved March 11, 2026) and republished in June 2026 with Gamida Cell as distributor and the product manufactured for Ayrmid Pharma. On November 2, 2026, Karyopharm Therapeutics filed for Chapter 11 and announced a planned merger with Ayrmid, which will serve as lead bidder in a court-supervised sale process expected to close in the first quarter of 2027, so the drug’s commercial owner may change again. No approval outside the U.S. has been announced, and no new indication was added in 2025 or 2026.

Common dosage forms

• Single-dose vial (approved product) — a preservative-free lyophilized powder containing 73 mg of motixafortide (as the acetate) with 26 mg mannitol, delivering 62 mg per vial by subcutaneous injection. Given by the transplant team during a filgrastim mobilization course, in the day before apheresis. Vials are stored refrigerated and protected from light.
• No pen, oral, or self-administered format exists — label-mandated premedication and post-dose observation mean it is not dispensed for home use.
• Laboratory reagent — reagent suppliers list motixafortide (BL-8040, BKT140) as lyophilized powder for in vitro CXCR4 work, typically under the development code rather than the brand name.

Key considerations

• Regulatory status — the FDA Approved status reflects Aphexda’s approval (NDA 217159, September 8, 2023) for one narrow, hospital-administered indication: stem cell mobilization with filgrastim before autologous transplant in multiple myeloma. The label has no pediatric indication and no approval in leukemia, pancreatic cancer, or sickle cell disease.
• Safety signals in the label — warnings cover anaphylactic shock and hypersensitivity reactions (mandatory premedication and post-dose monitoring), frequent injection-site reactions, leukocytosis requiring white-cell monitoring, the possibility of mobilizing tumor cells from marrow (with an explicit statement that it is not intended for leukemia patients), and embryo-fetal toxicity based on animal data; breastfeeding is advised against.
• Evidence gaps — the approval rests on a single Phase 3 of 122 randomized patients with an apheresis-yield endpoint, not a survival endpoint. The oncology results (AML, pancreatic cancer) are uncontrolled Phase 2 data, and the sickle cell results are unpublished conference presentations from 10 trial patients plus small real-world series.
• Naming confusions — BL-8040, BKT140, TN14003, and 4F-benzoyl-TN14003 are all the same molecule; parent T140 and related analogs (TC14012, TE14011) are different compounds. Motixafortide is a peptide and should not be confused with plerixafor (Mozobil), a bicyclam small molecule used for the same purpose, or with mavorixafor (Xolremdi), an oral small-molecule CXCR4 antagonist approved in 2024 for WHIM syndrome.