APHEXDA MOTIXAFORTIDE 62 mg/1.7mL Injection, Powder, Lyophilized, For Solution, 1 vial
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Other immunostimulants class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Motixafortide injection is used with filgrastim to help get cells ready for stem cell transplant in patients withmultiple myeloma. Motixafortide is in a class of medications called hematopoietic stem cell mobilizers. It works by increasing the number of stem cells in blood stream to be available for removal as part of the stem cell transplant process.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
-
UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J2277 | $26.479 / J2277 unit | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Aphexda 62 mg/1.7mLthis 73441-0062-01 | Gamida | 1 vial | — | — | FDA listed | — |
| Aphexda 62 mg/1.7mL 82737-0073-01 | BioLineRx | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12257285 ↗ | Drug product | — | Dec 29, 2041 |
| US 12268725 ↗ | Drug product | — | Dec 29, 2041 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Sep 8, 2028 |
| ODE-442 | Orphan Drug Exclusivity (7-year) | Sep 8, 2030 |
Is there a generic version of APHEXDA 62 MG VIAL?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73441-0062-01 You're viewing this | 1 VIAL, GLASS in 1 CARTON (73441-062-01) / 1.7 mL in 1 VIAL, GLASS | 2025-06-15 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Does this product have a billing J-code?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. APHEXDA, a hematopoietic stem cell mobilizer, is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Initiate APHEXDA treatment after filgrastim has been administered daily for 4 days. ( 2.1 ) Recommended dosage is 1.25 mg/kg actual body weight by subcutaneous injection 10 to 14 hours prior to initiation of apheresis. ( 2.2 ) A second dose of APHEXDA can be administered 10 to 14 hours prior to a third apheresis. ( 2.2 ) See Full Prescribing Information for instructions on preparation and administration.
2.1Important Dosing Information Premedicate all patients before each dose of APHEXDA to reduce the risk of hypersensitivity and injection site reactions: Administer diphenhydramine (12.5 mg intravenously or 25 mg to 50 mg orally, or another H1-antihistamine), an H2 blocker (e.g., famotidine), and a leukotriene inhibitor (e.g., montelukast) approximately 30 to 60 minutes before injection of APHEXDA. The addition of an analgesic medication (e.g., acetaminophen) to the premedication regimen is recommended. Administer filgrastim 10 mcg/kg subcutaneously once daily for 4 days prior to the first dose of APHEXDA and on each day prior to each apheresis.
2.2Recommended Dosage The recommended dosage of APHEXDA is 1.25 mg/kg administered via slow (approximately 2 minutes) subcutaneous injection 10 to 14 hours prior to the initiation of the first apheresis. Dosing is based on actual body weight. A second dose of APHEXDA can be administered 10 to 14 hours before a third apheresis, if necessary.
2.3Preparation and Administration Use aseptic technique to prepare and administer APHEXDA: More than one vial may be needed for a full dose. Calculate the dose, the total volume of reconstituted APHEXDA solution required, and number of APHEXDA vials required based on patient's actual body weight. Remove the APHEXDA vial(s) from the refrigerator and allow to reach room temperature at 20°C to 25°C (68°F to 77°F) for at least 30 minutes.
Reconstitute each vial with 2 mL of 0.45% Sodium Chloride Injection, USP at room temperature (20°C to 25°C (68°F to 77°F)) resulting in a concentration of 36.5 mg/mL of APHEXDA and permitting withdrawal of up to 1.7 mL (62 mg). Alternatively, you can reconstitute each vial with 1 mL of Sterile Water for Injection, USP and 1 mL of 0.9% Sodium Chloride Injection, USP. Gently swirl and invert for up to 3 minutes slowly until completely dissolved.
Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear clear and colorless. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates.
If needed, store the reconstituted APHEXDA solution refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 24 hours protected from light. Withdraw the required injection volume of APHEXDA from the vial(s) into an appropriately sized syringe. Each injection volume should not exceed 2 mL.
Divide doses requiring greater than 2 mL into multiple syringes to allow different injection sites. Administration Administer subcutaneous injection into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites.
An injection should never be given into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 5 cm diameter circle around the navel. If more than one injection is needed for a single dose of APHEXDA, the injection sites should be at least 2 cm apart from previous injection locations.
Discard unused portion of the drug. Monitor patients for one hour after administration [see Warnings and Precautions (5.1) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For injection: 62 mg as a white to off-white lyophilized powder in a single-dose vial for reconstitution. For Injection: 62 mg as a lyophilized powder in a single-dose vial for reconstitution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide [see Warnings and Precautions (5.1) ] . History of serious hypersensitivity reaction to APHEXDA. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Anaphylactic Shock and Hypersensitivity Reactions: Premedicate all patients with a combination of an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor prior to each APHEXDA dose. Administer APHEXDA in a setting where personnel and therapies are available for immediate treatment. Observe for signs and symptoms and manage promptly.
( 2.1 , 2.3 , 5.1 ) Injection Site Reactions: The addition of analgesic premedication (e.g., acetaminophen) is recommended. ( 5.2 ) Tumor Cell Mobilization in Patients with Leukemia: APHEXDA may mobilize leukemic cells and should not be used in leukemia patients. ( 5.3 ) Leukocytosis: Increased circulating leukocytes have been observed.
Monitor white blood cell counts during APHEXDA use. ( 5.4 ) Potential for Tumor Cell Mobilization: Tumor cells may be released from marrow during HSC mobilization with APHEXDA and filgrastim. Effect of reinfusion of tumor cells is unknown.
( 5.5 ) Embryo-fetal Toxicity: Can cause fetal harm. Advise women of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 )
5.1Anaphylactic Shock and Hypersensitivity Reactions Anaphylactic shock occurred in 0.7% of APHEXDA-treated patients in clinical studies (n=407). The time to anaphylactic shock was between 5 minutes and 30 minutes after drug administration. Hypersensitivity reactions occurred in 7.6% of APHEXDA-treated patients in the GENESIS study.
In addition, pruritus, flushing, urticaria, rash, erythema, vomiting, nausea and chills have been reported. Premedicate all patients prior to each dose of APHEXDA 30-60 minutes prior to administration with a triple-drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor [see Dosage and Administration (2.1) ] . Patients receiving concomitant negative chronotropic drugs (e.g., beta blockers) may be more at risk for hypotension in case of hypersensitivity reaction.
When appropriate, beta blockers should be replaced with non-chronotropic drugs. Administer APHEXDA only in a setting where personnel and therapies are immediately available for the treatment of anaphylaxis and other systemic reactions. Monitor patients for signs or symptoms of hypersensitivity reactions for one hour following administration of APHEXDA and manage reactions promptly.
5.2Injection Site Reactions Injection site reactions were reported in 73% of patients receiving APHEXDA in the GENESIS trial. Symptoms of injection site reactions included pain, erythema, pruritus, bruising, discomfort, induration, mass, nodule, rash, swelling, and urticaria. Among 92 patients treated with APHEXDA, the highest severity of the reactions was severe in 9%.
Premedicate with an analgesic medication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments postdose, as needed.
5.3Tumor Cell Mobilization in Patients with Leukemia For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
5.4Leukocytosis Administration of APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
5.5Potential for Tumor Cell Mobilization When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
5.6Embryo-fetal Toxicity Based on its mechanism of action, APHEXDA can cause fetal harm when administered to a pregnant woman. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development. Advise preg…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in other sections of the labeling: Anaphylactic Shock and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Injection Site Reactions [see Warnings and Precautions (5.2) ] Potential for Tumor Cell Mobilization in Patients in Leukemia [see Warnings and Precautions (5.3) ] Leukocytosis [see Warnings and Precautions (5.4) ] Potential for Tumor Cell Mobilization [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence >20%) are injection site reactions, injection site pain, injection site erythema, injection site pruritus, pruritus, flushing, and back pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gamida Cell at (844) 477-7478 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of APHEXDA was evaluated in the GENESIS study based on data from 92 patients with multiple myeloma who received at least one dose of APHEXDA 1.25 mg/kg subcutaneously and filgrastim and 42 patients who received placebo and filgrastim for mobilization of hematopoietic stem cells for collection and apheresis [see Clinical Studies (14) ] .
The premedication regimen changed during the conduct of the trial as evidence of hypersensitivity reactions was noted. Of the 92 patients who received at least one dose of APHEXDA, 14 patients received the triple-drug premedication regimen and 78 did not receive the triple-drug premedication regimen (either received no premedication or another premedication regimen). Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA in combination with filgrastim.
Serious adverse reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. One patient did not receive the 5 th dose of filgrastim due to an elevated white blood cell count following administration of APHEXDA. The most common adverse reactions occurring in GENESIS (>20% and at least 2% higher than the filgrastim + placebo arm) were injection site reactions (pain, erythema and pruritus), pruritus, flushing, and back pain.
Table 1 summarizes the common adverse reactions in GENESIS. Table 1: Common Adverse Reactions in Patients with Multiple Myeloma During Hematopoietic Stem Cell Mobilization and Apheresis in GENESIS Adverse reactions that occurred in ≥10% in APHEXDA-treated patients and ≥2% more than placebo-treated patients. APHEXDA and Filgrastim n=92 % Placebo and Filgrastim n=42 % All Grades Grade ≥3 All reactions were grade 3.
All Grades Grade ≥3 Injection site reactions Injection site reactions includes: injection site bruising, injection site discomfort, injection site erythema, injection site induration, injection site mass, injection site nodule, injection site pain, injection site pruritus, injection site rash, injection site swelling, injection site urticaria, injection site cellulitis and injection related reaction. 73 8 5 0 Injection site pain 53 7 5 0 Injection site erythema 27 0 0 0 Injection site pruritus 24 0 0 0 Pruritus 38 11 0 0 Flushing Flushing includes hot flush.
33 7 0 0 Rash Rash includes: rash erythematous, rash maculo-papular, rash papular and rash pruritic. 16 0 5 0 Urticaria 14 1.1 0 0 Erythema 12 0 0 0 Back pain Back pain includes spinal pain and sacral pain. 21 0 17 0 Paresthesia (g) Paresthesia includes: paresthesia oral, hypoesthesia, hypoesthesia oral and burning sensation.
19 0 17 0 Hypokalemia 15 4.3 12 0 Nausea 14 0 12 0 Clinically relevant adverse reactions that occurred in the APHEXDA arm only in <10% of patients include dermatitis exfoliative generalized, ear swelling, pyrexia, chills, dizziness, tremor and hyperte…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on its mechanism of action, APHEXDA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data with APHEXDA use in pregnant women informing the risk of embryo-fetal toxicity. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development (see Data ) .
No animal studies have been conducted to evaluate the effect of motixafortide on reproduction and fetal development. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriages for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with motixafortide to evaluate its effect on reproduction and embryo-fetal development. Disruption of CXCR4/SDF-1 signaling in mice and other models caused increased embryo-fetal lethality, and impairment of vascularization, cardiac anomalies, reduced hematopoiesis, impaired bone marrow myelopoiesis, disorganized neural layers in cerebellum, and reduced neural innervation of limbs.
CXCR4/SDF-1 levels have been shown to play a key role in stimulating trophoblast proliferation and differentiation necessary for appropriate placental growth and function in humans.
8.2Lactation Risk Summary There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential serious adverse reactions in the breastfed child, advise females that breastfeeding is not recommended during the treatment with APHEXDA and for 8 days after the final dose.
8.3Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating APHEXDA. Contraception Females APHEXDA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with APHEXDA and for 8 days after the final dose [see Use in Specific Populations (8.1) ] .
8.4Pediatric Use The safety and effectiveness of APHEXDA have not been established in pediatric patients.
8.5Geriatric Use Of the total number of patients in the GENESIS study, 33.8% were ≥65 years old, while 1.25% were ≥75 years old in the APHEXDA arm. No overall differences in safety or effectiveness were observed between these patients and younger patients.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on its mechanism of action, APHEXDA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data with APHEXDA use in pregnant women informing the risk of embryo-fetal toxicity. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development (see Data ) .
No animal studies have been conducted to evaluate the effect of motixafortide on reproduction and fetal development. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriages for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with motixafortide to evaluate its effect on reproduction and embryo-fetal development. Disruption of CXCR4/SDF-1 signaling in mice and other models caused increased embryo-fetal lethality, and impairment of vascularization, cardiac anomalies, reduced hematopoiesis, impaired bone marrow myelopoiesis, disorganized neural layers in cerebellum, and reduced neural innervation of limbs.
CXCR4/SDF-1 levels have been shown to play a key role in stimulating trophoblast proliferation and differentiation necessary for appropriate placental growth and function in humans.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of APHEXDA have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of patients in the GENESIS study, 33.8% were ≥65 years old, while 1.25% were ≥75 years old in the APHEXDA arm. No overall differences in safety or effectiveness were observed between these patients and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Motixafortide is an inhibitor of the C-X-C Motif Chemokine Receptor 4 (CXCR4) and blocks the binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12). SDF-1α and CXCR4 play a role in the trafficking and homing of human hematopoietic stem cells to the marrow compartment. Once in the marrow, stem cell CXCR4 can help anchor these cells to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules.
Treatment with motixafortide resulted in leukocytosis, and elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation in mice, rats, dogs, and humans. Stem cells mobilized by motixafortide were capable of engraftment with long-term repopulating capacity in a rodent transplantation model.
12.2Pharmacodynamics In vitro studies showed that the concentration for half-maximal inhibition (IC 50 ) of motixafortide towards CXCR4 ranges from 0.42 – 4.5 nM, the binding affinity (K D ) is 7.9 pM and the dissociation rate (Kd) from the CXCR4 receptor is 3.38e-5 s-1 with receptor occupancy maintained over >72 hours. The pharmacodynamics of motixafortide was evaluated in clinical studies conducted in healthy volunteers, healthy donors paired with recipients with advanced hematological malignancies, and multiple myeloma patients.
Across all clinical studies, mobilization of CD34+ to peripheral blood was observed. In healthy volunteers after administration of motixafortide as monotherapy, CD34+ cell counts increased with time, reaching maximal levels at 16 hours postdose. Thereafter, CD34+ cell counts declined slightly but remained elevated well above baseline at the last observation timepoint 24 hours postdose.
Data on the fold increase in peripheral blood CD34+ cell count (cells/mcL) by apheresis day were evaluated in the placebo-controlled part of the GENESIS study. The fold increase in CD34+ cell count over the 24-hour period, from the day prior to the first apheresis (before filgrastim administration) to the next morning before filgrastim administration (12 hours after APHEXDA administration) is summarized in Table 2. During this 24-hour period, a single dose of motixafortide or placebo was administered 10 to 14 hours prior to apheresis.
Table 2: Fold Increase in Peripheral Blood CD34+ Cell Count following Pre-treatment with Filgrastim and Administration of APHEXDA in GENESIS APHEXDA and Filgrastim Placebo and Filgrastim Median Mean (SD) Median Mean (SD) 6.7 7.7 (7.5) 1.5 1.6 (0.7) Cardiac Electrophysiology A thorough QT study in 38 healthy volunteers showed APHEXDA prolongs the QTcI interval in a concentration-dependent fashion. At 1.7-fold the C max of the maximum approved recommended dose (1.25 mg/kg), the mean placebo-corrected QTcI change from baseline was 11 (90% CI: 8 to 14) msec.
12.3Pharmacokinetics The pharmacokinetics of motixafortide were evaluated using both noncompartmental and population PK approaches in various populations, including healthy volunteers, patients with acute myeloid leukemia, and patients with multiple myeloma. Subjects received single or multiple doses ranging between 0.24 mg/kg to 2 mg/kg of APHEXDA administered by subcutaneous injections using a weight-based (mg/kg) dosing strategy as monotherapy or in combination with filgrastim with or without chemotherapy. The PK characteristics of motixafortide following subcutaneous administration were similar across all study populations.
A population pharmacokinetic analysis was conducted using 2240 plasma motixafortide concentrations from 223 individuals, including 81 healthy subjects, 37 patients with acute myeloid leukemia, and 105 patients with multiple myeloma. Motixafortide pharmacokinetics following subcutaneous administration were adequately described by a 3-compartment model with first-order absorption, dose-dependent relative bioavailability, and linear elimination kinetics. Minimal to…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Motixafortide is an inhibitor of the C-X-C Motif Chemokine Receptor 4 (CXCR4) and blocks the binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12). SDF-1α and CXCR4 play a role in the trafficking and homing of human hematopoietic stem cells to the marrow compartment. Once in the marrow, stem cell CXCR4 can help anchor these cells to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules.
Treatment with motixafortide resulted in leukocytosis, and elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation in mice, rats, dogs, and humans. Stem cells mobilized by motixafortide were capable of engraftment with long-term repopulating capacity in a rodent transplantation model.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING APHEXDA (motixafortide) for injection is supplied as a white to off-white lyophilized powder in a single-dose vial for reconstitution. Each vial delivers 62 mg motixafortide free base. NDC 73441-062-01 (Carton containing one vial) Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light.
Discard prepared reconstituted solution after 24 hours storage under refrigeration 2°C to 8°C (36°F to 46°F) or at room temperature 20°C to 25°C (68°F to 77°F) protected from light.
📦 Storage and Handling ▾
Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Discard prepared reconstituted solution after 24 hours storage under refrigeration 2°C to 8°C (36°F to 46°F) or at room temperature 20°C to 25°C (68°F to 77°F) protected from light.
📋 Description ▾
11 DESCRIPTION APHEXDA for injection contains motixafortide, which is a hematopoietic stem cell mobilizer. The chemical name of the synthetic motixafortide acetate, the active pharmaceutical ingredient, is N-(4-Fluoro-benzoyl)-L-arginyl-L-arginyl-[L-3-naphthyl)alanyl]-L-cysteinyl-L-tyrosyl 5 -L-citrullinyl-L-lysyl-D-lysyl-L-prolyl-L-tyrosyl 10 -L-arginyl-L-citrullinyl-L-cysteinyl-L-arginineamide, cyclic (4-13)-disulfide, acetate salt. Motixafortide acetate is a synthetic, cyclic peptide composed of a sequence of amino acids with the following structure: Sequence: Cit: Citrulline Nal: Naphthylalanine Fba: 4-Florobenzoic acid Counter Ion: Acetate Molecular weight: 2159.6 g/mol (as the free base) APHEXDA is supplied as a sterile white to off-white, preservative-free lyophilized powder in single-dose vials.
Each vial contains 73 mg of motixafortide (provided as motixafortide acetate) for reconstitution with 2 mL 0.45% saline, delivering 62 mg motixafortide per 1.7 mL. Motixafortide is present as a salt with 4 to 8.5 molar equivalents of acetate. The inactive ingredients include 26 mg of mannitol and hydrochloric acid for pH adjustment.
Reconstitution with 2 mL of 0.45% sodium chloride for injection (or 1 mL water for injection + 1 mL 0.9% sodium chloride for injection) yields a clear solution of 36.5 mg/mL motixafortide, pH 5.8 to 7.5. Chemical Structure Chemical Structure Chemical Structure Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients of the risk of anaphylactic and hypersensitivity reactions (such as pruritus, flushing, urticaria, rash, vomiting, nausea and chills) during and after APHEXDA injection and to immediately report such signs and symptoms to healthcare professionals [see Warnings and Precautions (5.1) ] . Advise patients that APHEXDA may cause injection site reactions, such as pain, redness, and swelling [see Warnings and Precautions (5.2) , Adverse Reactions (6.1 , 6.2) ] . Advise females of reproductive potential to use effective contraceptive methods during APHEXDA treatment and for 8 days after the administration of APHEXDA [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ] .
Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with APHEXDA [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ]. Advise women that breastfeeding is not recommended during treatment with APHEXDA and for 8 days following the last dose [see Use in Specific Populations (8.2) ] .