Publications
The published evidence
Vepoloxamer and poloxamer 188 have been studied in peer-reviewed literature for over three decades across cardiovascular, neurological, trauma and oncology supportive-care indications. These papers demonstrate the breadth of applicability of Vepoloxamer and the depth of the research performed by the academic community.
Key publication library
★ marks landmark citations.
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| Publication | Indication | Material Used |
|---|---|---|
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The pathobiology of mucositis ★
Establishes the five-phase model of mucositis — initiation, primary damage response, signal amplification, ulceration, healing — reframing OM from epithelial injury to an ROS-initiated, cytokine-amplified submucosal process.
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Oral Mucositis Review |
— |
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Avasopasem manganese treatment for severe oral mucositis from chemoradiotherapy for locally advanced head and neck cancer: phase 3 randomized controlled trial (ROMAN) ★
455 randomized / 407 analyzed: SOM incidence 54% vs 64% (RR 0.84, 95% CI 0.71–1.00, p=0.045), with reduced SOM duration and delayed onset. Received an FDA Complete Response Letter.
|
Competitive Landscape Phase 3 clinical |
— |
|
Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck ★
Of six Phase 3 oral mucositis trials, three succeeded (avasopasem, palifermin ×2) and three failed (dusquetide, iseganan, clonidine); identifies the trial-design features that separate them.
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Competitive Landscape Review |
— |
|
Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer ★
In 576 IMRT-treated head & neck cancer patients, 360 (62%) developed severe oral mucositis, associated with feeding-tube placement, hospitalization, weight loss and opioid use.
|
Epidemiology Cohort study |
— |
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Mucositis-Related Morbidity and Resource Utilization in Head and Neck Cancer Patients Receiving Radiation Therapy With or Without Chemotherapy ★
76% reported severe mouth/throat soreness; 85% required opioids; 51% required a feeding tube; 37% were hospitalized (mean stay 4.9 days).
|
Epidemiology Prospective multicenter |
— |
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The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies ★
60–70% of head & neck chemoradiation patients develop WHO Grade 3–4 mucositis, initiating in the 15–30 Gy window. Only about one-third of the injury is direct DNA damage; the remainder is a ROS-driven cascade through NF-κB, DAMPs/TLR-4 and the ceramide pathway, ending in increased membrane permeability and breakdown of the epithelial cells.
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Oral Mucositis Review |
— |
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A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment
Frames radiation-induced OM as what happens when the biological challenge of chemoradiation exceeds the mucosa's physiologic protective capacity — making prevention a question of raising tissue resilience rather than blocking a single pathway.
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Oral Mucositis Review |
— |
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Pathogenesis and Amelioration of Radiation-Induced Oral Mucositis
Pathophysiology-based review of the available OM prevention strategies; concludes that interventions which are simultaneously effective, practical and affordable remain rare.
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Oral Mucositis Review |
— |
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Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis
Median incremental cost of severe OM was ~$17,244 per head & neck chemoradiation patient; total cost of care ~$35,756 with severe OM versus ~$18,512 without.
|
Epidemiology Cost of care |
— |
|
Direct observation of poloxamer 188 insertion into lipid monolayers ★
P188 inserts into lipid monolayers only below a threshold surface pressure and is squeezed out as the monolayer recovers — the biophysical basis for selective targeting of damaged membranes and for self-limiting action.
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Mechanism of Action Biophysics |
Grade not stated |
|
Nature of interactions between PEO-PPO-PEO triblock copolymers and lipid membranes: (I) Effect of polymer hydrophobicity on its ability to protect liposomes from peroxidation
High hydrophilicity is the key feature enabling protection of liposomes from peroxidation, attributed to retardation of membrane hydration dynamics.
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Mechanism of Action Biophysics |
Grade not stated |
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Poloxamer 188 facilitates the repair of alveolus resident cells in ventilator-injured lungs
P188 protected alveolar resident cells from necrosis and reduced ventilator-induced lung injury across live rats, isolated perfused lungs and wounded epithelial cells.
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Mechanism of Action Preclinical in vivo / in vitro |
Grade not stated |
|
Amphiphilic, tri-block copolymers provide potent, membrane-targeted neuroprotection
Established that triblock copolymer protection is membrane-targeted rather than receptor-mediated — the basis for cross-tissue generalization of the mechanism.
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Mechanism of Action Preclinical / in vitro |
Grade not stated |
|
Restoration of tumor vascular integrity by P188 improves chemotherapy and immunotherapy efficacy in triple negative breast cancer
In mouse models of aggressive breast cancer, P188 sealed leaky tumor blood vessels, tripling immune-cell entry into tumors, slowing tumor growth about 5-fold with immune-cell therapy, and halving chemotherapy side effects.
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Adjunctive Therapy Preclinical |
Other |
|
Differential effects of commercial-grade and purified poloxamer 188 on renal function ★
Purified P188, with low-molecular-weight species removed, did not raise serum creatinine above placebo, whereas commercial-grade P188 did — the renal risk is attributable to the LMW impurity fraction, not to the P188 backbone.
|
Purification / Safety PK / toxicology |
Purified vs. commercial |
|
Pharmacokinetics of a novel surface-active agent, purified poloxamer 188, in rat, rabbit, dog and man
Dose-proportional plasma concentrations across species; renal clearance accounts for 90% of total plasma clearance in man.
|
Purification / Safety PK / toxicology |
Vepoloxamer |
|
Effect of poloxamer 188 vs placebo on painful vaso-occlusive episodes in children and adults with sickle cell disease: a randomized clinical trial ★
EPIC (n=388, 66 hospitals, 12 countries): median time to last parenteral opioid 69.2 h vs 66.4 h — no significant difference. The trial did not support P188 for vaso-occlusive crisis.
|
Clinical — Sickle Cell Phase 3 clinical |
Vepoloxamer |
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Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial ★
In 255 patients, purified P188 shortened mean crisis duration by 8.8 hours (p=0.04), with larger effects in children ≤15 years (−21 h, p=0.01) and hydroxyurea users (−16 h, p=0.02).
|
Clinical — Sickle Cell Phase 3 clinical |
Vepoloxamer |
|
Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction
n=114: 38% reduction in median infarct size (16% vs 26% of LV, p=0.031), ejection fraction 52% vs 46% (p=0.020), reinfarction 1% vs 13% (p=0.016).
|
Clinical — Acute MI Phase 2 clinical |
Unpurified P188 |
|
Cardioprotection by poloxamer 188 is mediated through increased endothelial nitric oxide production ★
Identifies endothelium-derived nitric oxide as a required mediator of P188 cardioprotection — a mechanism extending beyond passive membrane sealing.
|
STEMI / Reperfusion In vitro |
Commercial P188 |
|
Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction ★
In 55 pigs, immediate intracoronary P188 cut infarct size from 41.1% to 13.9% (~66% reduction) and troponin I from 77.4 to 19.2 µg/L; delayed peripheral dosing and PEG control did not.
|
STEMI / Reperfusion Preclinical in vivo |
Grade not stated |
|
Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization
Sarcolemmal stabilization dissociates oxidative stress from cell death — membrane rupture, not ROS per se, is what kills the myocyte.
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STEMI / Reperfusion Preclinical in vivo |
Grade not stated |
|
Effects of Intravenous Infusion of Vepoloxamer on Left Ventricular Function in Dogs with Advanced Heart Failure ★
In dogs with microembolization-induced heart failure, Vepoloxamer raised ejection fraction by ~6–7 absolute points, sustained for at least one week; pulsed dosing extended benefit to three weeks with falling NT-proBNP and troponin I.
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Heart Failure Preclinical in vivo |
Vepoloxamer |
|
Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke ★
Vepoloxamer combined with tPA accelerated clot lysis and reduced infarct volume and neurovascular injury in a rat embolic stroke model beyond tPA alone.
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Ischemic Stroke Preclinical in vivo |
Vepoloxamer |
|
Treatment of stroke in aged male and female rats with Vepoloxamer and tPA reduces neurovascular damage
In 18-month-old male and female rats, Vepoloxamer + tPA administered 4 hours post-stroke significantly reduced infarct volume and neurological deficit vs. saline or either agent alone.
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Ischemic Stroke Preclinical in vivo |
Vepoloxamer |
|
Poloxamer 188 Protects Neurons against Ischemia/Reperfusion Injury through Preserving Integrity of Cell Membranes and Blood Brain Barrier
P188 preserved neuronal membrane integrity and reduced blood–brain-barrier permeability after cerebral ischemia/reperfusion.
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Ischemic Stroke Preclinical in vivo / in vitro |
Grade not stated |
|
Vepoloxamer improves functional recovery in rat after traumatic brain injury: A dose-response and therapeutic window study ★
100, 300 and 600 mg/kg all improved cognition; 300 mg/kg IV at 2 hours was optimal; efficacy retained out to 3 days post-injury.
|
Traumatic Brain Injury Preclinical in vivo |
Vepoloxamer |
|
Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188) ★
Vepoloxamer initiated 2 hours post-controlled-cortical-impact improved sensorimotor and cognitive recovery, with neuroprotective and anti-inflammatory effects.
|
Traumatic Brain Injury Preclinical in vivo |
Vepoloxamer |
|
Effects of poloxamer 188 on traumatic brain injury
Across 20 included studies, P188 restored membrane permeability, attenuated neuronal necrosis and apoptosis, and improved motor and behavioral outcomes in TBI models.
|
Traumatic Brain Injury Systematic review |
Grade not stated |
|
Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma
Foundational demonstration that P188 blocks mechanically-induced necrotic and apoptotic neuronal death via membrane resealing.
|
Traumatic Brain Injury In vitro |
Grade not stated |
|
Subcutaneous tri-block copolymer produces recovery from spinal cord injury
A single subcutaneous P188 injection 6 hours after severe guinea-pig cord compression restored nerve impulse conduction through the lesion and recovered a long-tract spinal reflex.
|
Spinal Cord Injury Preclinical in vivo |
Grade not stated |
|
The Use of Poloxamer 188 in Burn Injury Treatment: A Systematic Literature Review ★
PRISMA-compliant systematic review of P188 across thermal and electrical burn mechanisms.
|
Burn Injury Systematic review |
Grade not stated |
|
Poloxamer-188 Improves Capillary Blood Flow and Tissue Viability in a Cutaneous Burn Wound
P188 preserved capillary perfusion and tissue viability in a rat cutaneous burn — the canonical zone-of-stasis salvage result.
|
Burn Injury Preclinical in vivo |
Grade not stated |
|
Topical Poloxamer-188 Improves Blood Flow Following Thermal Injury in Rat Mesenteric Microvasculature
Topical P188 cut capillaries with abnormal flow from 62% to 23% and venules from 54% to 34% — direct reversal of sludging and stasis.
|
Burn Injury Preclinical in vivo |
Grade not stated |
|
Poloxamer 188 Prolongs Survival of Hypotensive Resuscitation and Decreases Vital Tissue Injury After Full Resuscitation ★
Survival rose from 0% to 75% in 50% volume-controlled hemorrhage (p<0.001); survivable hypotensive resuscitation extended by more than 3 hours; myocardial, pulmonary, small-bowel, renal and hepatic necrosis prevented.
|
Hemorrhagic Shock Preclinical in vivo |
Vepoloxamer |
|
Severe Controlled Hemorrhage Resuscitation With Small Volume Poloxamer 188 in Sedated Miniature Swine
After 60% blood-volume hemorrhage, a single 1.33 mL/kg bolus of P188 with no other fluids improved outcome vs. vehicle.
|
Hemorrhagic Shock Preclinical in vivo |
Grade not stated |
|
Autoresuscitation of Poloxamer 188 in Pigs with Traumatic Severe Hemorrhage
In swine with traumatic severe hemorrhage, small-volume P188 supported autoresuscitation and improved hemodynamic recovery without conventional volume resuscitation.
|
Hemorrhagic Shock Preclinical in vivo |
Grade not stated |
|
Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs ★
Chronic poloxamer infusion in dystrophic dogs reduced myocardial fibrosis, blocked cardiac troponin I and BNP elevation, and fully prevented left-ventricular remodeling.
|
Muscular Dystrophy Preclinical in vivo |
Grade not stated |
|
Dystrophic heart failure blocked by membrane sealant poloxamer ★
Intravenous P188 in mdx mice instantly improved ventricular geometry and blocked acute cardiac failure under dobutamine stress.
|
Muscular Dystrophy Preclinical in vivo |
Grade not stated |
|
Poloxamer 188 has a deleterious effect on dystrophic skeletal muscle function
CONTRASTING RESULT: after two weeks of P188 dosing, force drop after eccentric contractions was significantly greater than in saline controls.
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Muscular Dystrophy Preclinical in vivo |
Grade not stated |
|
Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo
P188 blocked carboxyfluorescein release from electropermeabilized skeletal muscle in vivo, while a neutral dextran control only retarded it — size and chemistry specificity, not a bulk osmotic effect.
|
Limb / Electrical Injury Preclinical in vivo |
Grade not stated |
Vepoloxamer is an investigational drug and has not been approved by the U.S. Food and Drug Administration for any use.
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