Gene therapy | |
---|---|
Target gene | Interferon alfa-2b |
Clinical data | |
Trade names | Adstiladrin |
Other names | Nadofaragene firadenovec-vncg, Instilidrin, rAd-IFN/Syn3 |
MedlinePlus | a623062 |
License data | |
Routes of administration | Intravesical |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
UNII | |
KEGG |
Nadofaragene firadenovec, sold under the brand name Adstiladrin, is a gene therapy for the treatment of bladder cancer. [1] [3] [4] It is a non-replicating (cannot multiply in human cells) adenoviral vector-based gene therapy. [3]
The most common adverse events including laboratory abnormalities, include increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, and pyrexia. [4]
Nadofaragene firadenovec was approved for medical use in the United States in December 2022. [3] [4] [5]
Nadofaragene firadenovec is indicated for the treatment of adults with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. [1] [3]
The safety and effectiveness of nadofaragene firadenovec was evaluated in a multicenter clinical study (Study CS-003 (NCT02773849)) that included 157 participants with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, 98 of whom had BCG-unresponsive carcinoma in situ with or without papillary tumors and could be evaluated for response. [3] [4] Participants received nadofaragene firadenovec once every three months for up to twelve months, or until unacceptable toxicity to therapy or recurrent high-grade non-muscle-invasive bladder cancer. [3] [4] Overall, 51% of enrolled participants using nadofaragene firadenovec therapy achieved a complete response (the disappearance of all signs of cancer as seen on cystoscopy, biopsied tissue, and urine). [3] The median duration of response was 9.7 months. [3] Forty-six percent of responding participants remained in complete response for at least one year. [3] The major efficacy outcome measures were complete response at any time and duration of response. [4] Complete response was defined as negative cystoscopy with applicable transurethral resection of bladder tumor and biopsies and urine cytology. [4] Random bladder biopsies of five sites were conducted in participants remaining in complete response at twelve months. [4]
The US Food and Drug Administration (FDA) granted the application for nadofaragene firadenovec priority review, breakthrough therapy, fast track, and orphan drug designations. [3] [4] The FDA granted approval of Adstiladrin to Ferring Pharmaceuticals A/S. [3]
Nadofaragene firadenovec is the international nonproprietary name (INN). [6]
The Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as soon after birth as possible. In areas where tuberculosis is not common, only children at high risk are typically immunized, while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunized, but are frequently exposed, may be immunized, as well. BCG also has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacterial infections. Additionally, it is sometimes used as part of the treatment of bladder cancer.
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.
Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become malignant.
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A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
Denise Louise Faustman is an American physician and medical researcher. An associate professor of medicine at Harvard University and director of the Immunobiology Laboratory at Massachusetts General Hospital, her work specializes in diabetes mellitus type 1 and other autoimmune diseases. She has worked at Massachusetts General Hospital in Boston since 1985.
Valrubicin (N-trifluoroacetyladriamycin-14-valerate, trade name Valstar) is a chemotherapy drug used to treat bladder cancer. Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder.
Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity.
Ferring Pharmaceuticals is a Swiss multinational biopharmaceutical company specialising in areas such as reproductive health, maternal health, gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 years.
Transitional cell carcinoma is a type of cancer that arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the urinary system; in that case, it is also called urothelial carcinoma. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. Symptoms of urothelial carcinoma in the bladder include hematuria. Diagnosis includes urine analysis and imaging of the urinary tract (cystoscopy).
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Lloyd John Old was one of the founders and standard-bearers of the field of cancer immunology. When Old began his career in 1958, tumor immunology was in its infancy. Today, cancer immunotherapies are emerging as a significant advance in cancer therapy.
Oportuzumab monatox is an experimental anti-cancer medication. Chemically, oportuzumab is a single chain variable fragment of a monoclonal antibody which binds to epithelial cell adhesion molecule. Oportuzumab is fused with Pseudomonas aeruginosa exotoxin A.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.
Pralsetinib, sold under the brand name Gavreto, is a medication approved for RET mutation-positive medullary thyroid cancer (MTC) and RET fusion-positive differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) therapy. Pralsetinib is a tyrosine kinase inhibitor. It is taken by mouth.
Dr. Alvaro Morales, MD, FRCSC is a Colombian-Canadian urologist, surgeon and Member of the Order of Canada who is noted for his work in the fields of cancer research and testosterone deficiency. He is particularly known for his pioneering work using Bacillus Calmette–Guérin (BCG) to treat bladder cancer, the first proven immunotherapy for cancer. A 2018 article in the Canadian Urological Association Journal said Morales' cancer research "changed the course of urology" and described him as a "living legend."
Nogapendekin alfa inbakicept, sold under the brand name Anktiva, is a fixed-dose combination medication used for the treatment of bladder cancer. It is an interleukin-15 receptor agonist. It is given in combination with Bacillus Calmette-Guérin via intravesical drug delivery. It contains nogapendekin alfa, a human IL-15N72D variant; and inbakicept, an interleukin 15 receptor subunit alpha.
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