About Gleolan

About Gleolan

What is GleolanTM?

  • Gleolan is an orally administered optical imaging agent that contains aminolevulinic acid HCL (ALA).
  • Gleolan is used as an adjunct for visualization of malignant tumors during surgery
  • Gleolan is supplied as a lyophilized powder that is reconstituted by a healthcare professional and given to the patient 3 hours (range 2-4 hours) prior to anesthesia.

How Does Gleolan Work?

  • The active substance in Gleolan, ALA, is orally administered to the patient 3 hours (range 2 to 4 hours) prior to anesthesia.
  • Malignant glioma cells take up more ALA and more rapidly metabolize it into protoporphyrin IX (PpIX) which accumulates in high grade glioma to a greater extent than in surrounding tissue.
  • PpIX is a key precursor in the heme biosynthesis pathway with a unique fluorescent characteristic*
  • Upon illumination with blue light, wavelength of 375 to 440 nm, the PpIX in tumor tissue fluoresces with red-violet color which can be seen in the microscope with appropriate emission filters (620 to 710 nm) distinguishing it from non-fluorescing tissue which appears blue.

In some cases, Gleolan under blue light allows the neurosurgeon to see malignancy they may not have been able to see under standard white light.

(False negatives and false positives may occur.  Non-fluorescing tissue in the surgical field does not rule out the presence of tumor in patents with glioma.  Fluorescence may be seen in areas of inflammation or metastases from other tumor types.)

  • Gleolan should only be used by neurosurgeons that have completed the Gleolan Neurosurgeon Training Program from NX Development Corp. Click here to find out how to get trained.

Real-time visualization of tumor tissue with high predictive accuracy

  • Gleolan provides surgeons improved visualization of malignant tissue in real-time. (Table 1)
  • Pivotal trials demonstrated 95% positive predictive value (PPV) in identifying malignant tissue (WHO Grades III or IV)—correlating with a high degree of precision to what the pathologist observed3. (Table 2)

Gleolan Offers:

Predictive accuracy

Gleolan fluorescence is highly predictive of malignant tumors. In patients with confirmed high-grade glioma randomized to the ALA fluorescence arm, presence of fluorescence at a biopsy level was compared to tumor status using histopathology as the reference standard (Table 1). In patients with low-grade glioma (WHO Grade I or II) who received ALA, 9 out of 10 biopsies were false negative.

The extent of resection among patients with confirmed high-grade glioma in the ALA fluorescence arm was compared to that among patients in the control arm, with the “completeness” of resection being determined by a central blinded read of early post-surgical MRI. Percentage of patients who had “completeness” of resection was 64% in the ALA arm and 38% in the control arm, with the difference of 26% [95% CI:(16%, 36%)]2

Clinical usefulness

Additional malignant tumors may be visualized with Gleolan fluorescence-guided surgery that is not observed under normal procedures. (False negatives and false positives may occur. Non-fluorescing tissue in the surgical field does not rule out the presence of tumor in patients with glioma. Fluorescence may be seen in areas of inflammation or metastases from other tumor types.)

Convenience of oral administration

Recommended dose of 20mg/kg administered orally, 3 hours (range 2 to 4 hours) prior to anesthesia for real time visualization of malignant tumor tissue under blue light.  Reduce exposure to sunlight or room lights for 48 hours after oral administration of Gleolan.

Established safety profile

The safety of Gleolan is supported by 5 open label clinical trials.  A decade of clinical use in over 40 countries and over 60,000 patients (See Important Safety Information).

Predictability

Provides high PPV under blue light; clinical trials demonstrated 95% PPV.2-4

Compatibility

Integrates with your standard of care (SOC) and operative procedures (iMRI, neuronavigation, etc.), so the flow of surgery is not interrupted.

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Safety Information

Contraindications:

Do not use Gleolan in patients with:

  • Hypersensitivity to the active substance
  • Acute or chronic types of porphyria

Warnings and precautions:

Due to the risk of phototoxic reactions, do not administer phototoxic drugs for 24 hours during the perioperative period. Reduce exposure to sunlight or room lights for 48 hours after administration of Gleolan.

Errors may occur with the use of Gleolan for intraoperative visualization of malignant glioma, including false negatives and false positives. Non-fluorescing tissue in the surgical field does not rule out the presence of tumor in patients with glioma. Fluorescence may be seen in areas of inflammation or metastases from other tumor types.

Hypersensitivity reactions, including serious hypersensitivity reactions have occurred; these reactions include anaphylactic shock, swelling, and urticaria. Always have cardiopulmonary resuscitation personnel and equipment readily available and monitor all patients for hypersensitivity reactions

Adverse reactions:

  • Adverse reactions that occurred in >1% of patients in the week following surgery were: pyrexia, hypertension, nausea, and vomiting
  • Adverse reactions occurring in the first 6 weeks after surgery in <1% of patients were: chills, photosensitivity reaction, solar dermatitis, hypotension, abnormal liver function test, and diarrhea
  • Neurologic events occurring in >1% of patients included: aphasia (8%), hemiparesis (7.8%), hemianopsia (3.2%), headache (2.7%), seizure (1.9%), hemiplegia (1.9%), monoparesis (1.3%) and hypoesthesia (1.1%)
  • Elevated liver enzymes (ALT and GGT) occurred in 15.8% and 11.6%, respectively) within first week after surgery which remained elevated in some patients 6 weeks after surgery

Please see Full Prescribing Information for additional important safety information.

Table 2

REFERENCEs

2 Stummer, et al., Lancet Oncology 7: 392-401, 2006. Fluorescence-guided surgery with 5-aminolevulinic, acid for resection of malignant glioma: A randomised controlled multicentre phase III trial.

3 Stummer et al., Neurosurgery 74:310-320, 2014 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. doi: 10.1227/NEU.0000000000000267.

4Nabavi et al., Neurosurgery 65:1070-1077, 2009 Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase II study. doi: 10.1227/01.NEU.0000360128.03597. C7.

Important Safety Information
GleolanTM is an optical imaging agent indicated in patients with glioma (suspected WHO Grades III or IV on preoperative imaging) as an adjunct for the visualization of malignant tissue during surgery. Gleolan can only be used by neurosurgeons who have completed a training program on use of fluorescence in surgery provided by NXDC, the distributor.

Contraindications

Do not use Gleolan in patients with:

  • Hypersensitivity to the active substance
  • Acute or chronic types of porphyria

Warnings and Precautions

Due to the risk of phototoxic reactions, do not administer phototoxic drugs for 24 hours during the perioperative period. Reduce exposure to sunlight or room lights for 48 hours after administration of Gleolan.

Errors may occur with the use of Gleolan for intraoperative visualization of malignant glioma,
including false negatives and false positives. Non-fluorescing tissue in the surgical field does not
rule out the presence of tumor in patients with glioma. Fluorescence may be seen in areas of inflammation or metastases from other tumor types.

Hypersensitivity reactions, including serious hypersensitivity reactions have occurred; these
reactions include anaphylactic shock, swelling, and urticaria. Always have cardiopulmonary resuscitation personnel and equipment readily available and monitor all patients for hypersensitivity reactions.

Adverse Reactions

Adverse reactions occurring in >1% of patients in the week following surgery were pyrexia, hypotension, nausea, and vomiting.

Nervous system disorders occurred in 29% of patients within the first week after surgery and events occurring in >1% of patients included: aphasia (8%), hemiparesis (7.8%), hemianopsia (3.2%), headache (2.7%), seizure (1.9%), hemiplegia (1.9%), monoparesis (1.3%) and hypoesthesia (1.1%). Brain edema occurred in <1% of patients in the first 6 weeks after surgery. In a randomized clinical trial, the numbers of serious neurologic adverse events in the post operative period were higher in patients randomized to ALA fluorescence arm compared to the control arm. An imbalance was notable for the adverse events aphasia, ataxia, convulsion and hemianopsia and is likely related to the higher amount of brain resection performed in the ALA arm. At longer follow up periods, the numbers between the two arms appeared similar.

Worsening of >= 2 Common Toxicity Criteria grades in alanine aminotransferase and gamma-glutamyl transferase occurred in 15.8% and 11.6% of patients, respectively, within the first week after surgery. Absolute levels ranged from 2 times to greater than 10 times the upper limit of normal for each parameter. At 6 weeks, these measurements remained elevated in 2.9% and 7.5% of patients, respectively. There were no cases of liver failure.

Drug-Drug Interactions

See information under Warning and Precautions regarding phototoxic reactions.

Please see Full Prescribing Information