What Is hexaminolevulinate?
hexaminolevulinate is an FDA-approved medication used during cystoscopy to help detect bladder cancer. It is also known by its brand names, Hexvix and Cysview. This medication is a photosensitizer, meaning it makes cells sensitive to light. When hexaminolevulinate is instilled directly into the bladder, cancerous cells absorb and convert it into a fluorescent substance more readily than healthy cells. During a subsequent cystoscopy, the bladder is illuminated with a specific blue light. The fluorescent substance in the abnormal cells then glows, making these cancerous or precancerous tissues easier for a surgeon to visualize and remove.
Beyond its approved use in bladder cancer detection, hexaminolevulinate is currently being investigated in clinical trials for other conditions. These include various forms of bladder cancer, such as High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma and Non-muscle-invasive Bladder Cancer. Researchers are also studying its potential use in cervical conditions like Cervical Dysplasia and Cervical Intraepithelial Neoplasia, as well as in Colon Cancer, Colorectal Cancer, and Genital Lichen Planus.
Uses and Conditions Under Study
hexaminolevulinate is primarily used and studied for its role in detecting various types of cancer and precancerous conditions, particularly those affecting the bladder and other epithelial tissues. Clinical trials have involved 5,760 participants across 14 trials since 2003.
- Bladder Cancer: This medication is extensively studied for bladder cancer, including Non-muscle-invasive Bladder Cancer and High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma. These conditions involve abnormal cell growth in the bladder lining. hexaminolevulinate helps surgeons identify these abnormal cells more clearly during a procedure called blue light cystoscopy, which can lead to more complete removal of cancerous tissue. A total of 10 trials have investigated hexaminolevulinate for bladder cancer and related urothelial carcinomas.
- Cervical Conditions: hexaminolevulinate is also being investigated for precancerous changes in the cervix, specifically Cervical Dysplasia and Cervical Intraepithelial Neoplasia. These conditions involve abnormal cell growth on the surface of the cervix that could potentially develop into cancer. The photosensitizing properties of hexaminolevulinate may help in the visualization and treatment of these abnormal cervical cells. Two trials are exploring its use in these cervical conditions.
- Gastrointestinal Cancers: The drug is under study for Colon Cancer and Colorectal Cancer. These are cancers that affect the large intestine. Similar to its use in bladder cancer, hexaminolevulinate might help highlight cancerous cells in the gastrointestinal tract, potentially aiding in their detection or removal. Two trials have focused on these types of cancer.
- Genital Lichen Planus: This is a chronic inflammatory skin condition that can affect the genital area. One trial is exploring hexaminolevulinate for this condition, suggesting a potential role in modulating inflammatory responses or targeting affected tissues.
- Pharmacokinetics: One trial has focused on the pharmacokinetics of hexaminolevulinate. These studies examine how the body absorbs, distributes, metabolizes, and excretes the drug, providing important information about its safety and optimal dosing.
Dosing
hexaminolevulinate is administered as an intravesical solution, meaning it is instilled directly into the bladder using a catheter. This allows the medication to come into direct contact with the bladder lining where cancerous or precancerous cells may be present. The instillation typically occurs for a specific duration, often around one hour, before a cystoscopic examination is performed.
Several strengths and volumes of hexaminolevulinate solution have been studied in clinical trials. Common doses include 85 mg in 50 mL of phosphate buffered saline, or 100 mg of hexaminolevulinate HCL. Another formulation involved 50 mL of hexaminolevulinate hydrochloride intravesical solution, with the concentration of the active ingredient not explicitly stated in that specific description. The medication is used in conjunction with blue light illumination during procedures like Photodynamic Diagnosis-Transurethral Resection of Bladder Tumor (PDD-TURBT) or blue light cystoscopy.
Various other formulations and concentrations, such as "MAL 3," "HAL 10, 3," "HAL 40, 12," and others, have also been investigated across different studies to determine optimal efficacy and safety profiles for specific conditions or diagnostic procedures.
Side Effects
In a clinical trial involving 68 patients treated with hexaminolevulinate, the most commonly reported side effects included muscle spasms and headache. These data are based on a single study where patients received hexaminolevulinate for diagnostic purposes.
- 4.4% of patients taking hexaminolevulinate experienced muscle spasms, compared to 0.0% on placebo.
- 4.4% of patients taking hexaminolevulinate experienced headache, compared to 13.3% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced haemorrhage, compared to 0.0% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced vaginal infection, compared to 0.0% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced dysmenorrhoea, compared to 0.0% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced pain, compared to 0.0% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced uterine pain, compared to 6.7% on placebo.
- 2.9% of patients taking hexaminolevulinate experienced back pain, compared to 0.0% on placebo.
Clinical Trial Results
Clinical trials have investigated hexaminolevulinate (also known as Hexvix or Cysview) for the diagnosis of bladder cancer and the treatment of cervical intraepithelial neoplasia (CIN).
Bladder Cancer Diagnosis
In a study (NCT00634621) evaluating the detection of bladder cancer lesions, the combination of white-light and blue-light cystoscopy with hexaminolevulinate detected 938 lesions. In comparison, white-light cystoscopy alone detected 12 lesions. Blue-light cystoscopy alone detected 220 lesions.
Another study (NCT02560584) focused on bladder cancer surveillance. In this study, 13 patients had histologically confirmed malignancy that was detected only by blue light cystoscopy with Cysview, and not by white light cystoscopy. Additionally, 9 patients had one or more carcinoma in situ (CIS) lesions detected only with blue light cystoscopy with Cysview, and not with white light cystoscopy.
A comparative study (NCT05600322) further explored the detection of bladder cancer. It found that 42 participants had histology-confirmed lesions (Ta, T1, or CIS) that were identified by Hexvix Blue Light Cystoscopy but were missed by White Light Cystoscopy. Furthermore, 11 subjects had at least one additional CIS lesion detected with Hexvix Blue Light Cystoscopy that was not found with White Light Cystoscopy.
Cervical Intraepithelial Neoplasia (CIN) Grade 1 Treatment
A trial (NCT00708942) investigated hexaminolevulinate photodynamic therapy for Cervical Intraepithelial Neoplasia (CIN) Grade 1. For complete response, 90.0% of patients treated with hexaminolevulinate ointment and LED diode illumination achieved a complete response, compared to 33.3% in the placebo ointment group. In another treatment arm, 57.1% of patients receiving hexaminolevulinate suppository with laser illumination had a complete response, compared to 40.0% in the placebo suppository group.
Regarding the eradication of HPV, 60.0% of patients treated with hexaminolevulinate suppository and laser illumination achieved HPV eradication, compared to 28.6% in the placebo suppository group. Hexaminolevulinate ointment with LED diode illumination resulted in HPV eradication for 50.0% of patients, compared to 33.3% in the placebo ointment group. An arm with no intervention reported 100% HPV eradication, which may reflect spontaneous regression or other factors.
Currently Recruiting Trials
Clinical trials are essential for advancing medical knowledge and finding new ways to treat diseases. For hexaminolevulinate, two studies are currently recruiting participants to further understand its use, particularly in bladder cancer. These trials offer opportunities for patients to contribute to medical research and potentially benefit from new approaches to care. One significant study, NCT05962541, is a Phase 4 trial sponsored by the University of Roma La Sapienza. This study is investigating whether using the Vesical Imaging-Reporting and Data System (VI-RADS) followed by Photodynamic Trans-urethral Resection of Bladder Tumours (PDD-TURBT) can help avoid secondary resections (Re-TURBT) in non-muscle-invasive bladder cancers (NMIBCs). The current standard of care often involves a primary TURBT followed by a repeat TURBT due to the possibility of residual disease. This trial aims to enroll 327 participants with Non-muscle-invasive Bladder Cancer, Non-Muscle Invasive Bladder Urothelial Carcinoma, or High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma, comparing the PDD-TURBT approach to the standard white light TURBT plus Re-TURBT. Another ongoing study, NCT02660645, is a registry study sponsored by Photocure. This trial, which does not have a specific phase designation, is gathering more information on the real-world use of Blue Light Cystoscopy with Cysview® (BLCC) in urologists' practices. The study is designed to observe and collect data on how BLCC is currently being used for patients with Bladder Cancer, with a substantial enrollment target of 4400 participants.Where to Participate
Participation in clinical trials for hexaminolevulinate is available across a wide geographic area, with study sites located in 23 different locations across 21 cities and 16 states. This broad reach helps ensure that many patients have the opportunity to join these important research efforts. The top cities with recruiting sites include:- Columbus, Ohio (2 sites)
- Los Angeles, California (2 sites)
- Palo Alto, California (1 site)
- San Francisco, California (1 site)
- Washington D.C., District of Columbia (1 site)
- Atlanta, Georgia (1 site)
- Chicago, Illinois (1 site)
- Evanston, Illinois (1 site)
- Indianapolis, Indiana (1 site)
- Kansas City, Kansas (1 site)