Indication and Mechanism

• ADSTILADRIN is indicated for adult patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

• It is a non-replicating adenoviral vector-based gene therapy that delivers the interferon alfa-2b gene to bladder cells, stimulating local production of interferon to fight cancer.

Dosing and Administration

• The recommended dose is 75 mL at a concentration of 3 x 10^11 viral particles/mL, administered by intravesical instillation once every 3 months.

• Premedication with an anticholinergic is recommended before each instillation.

• The medication should be retained in the bladder for 1 hour, with patients changing positions every 15 minutes.

Efficacy

• In clinical trials, 51% of patients achieved a complete response, with a median duration of response of 9.7 months.

• 46% of responding patients remained in complete response for at least one year.

Safety and Adverse Events

• Most common adverse events include increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, and urination urgency.

• Contraindicated in patients with hypersensitivity to interferon alfa or any component of the product.

Patient Education and Monitoring

• Patients should be advised to disinfect their urine for 2 days post-administration by adding bleach to the toilet before urinating.

• Patients should be monitored for complete response at 3 months; if no complete response or if cancer recurs, consider alternative treatments.

• Advise patients on reproductive potential to use effective contraception during treatment and for 6 months (females) or 3 months (males) after the last dose.

Practical Considerations

• ADSTILADRIN requires specific storage and handling; it should be stored frozen and thawed before administration.

• No reconstitution or dilution is required, simplifying preparation.

Thawing and Storage Instructions for ADSTILADRIN

Frozen → Thawing at Room Temperature (up to 25°C/77°F)

• Outside the cardboard nest: Approximately 3-5 hours

• Inside the cardboard nest: Approximately 8-10 hours

Frozen → Thawing in the Refrigerator (up to 8°C/46°F)

• Outside the cardboard nest: Approximately 4-5 hours

• Inside the cardboard nest: Approximately 11-13 hours

Bringing Thawed ADSTILADRIN to Room Temperature

• Outside the cardboard nest: Approximately 2 hours 30 minutes
• Inside the cardboard nest: Approximately 6 hours

Important Handling Instructions

• Temperature: Do not expose the vials to temperatures higher than 25°C/77°F.

• Light Protection: Protect the vials from light at all times.

• Refreezing: Do not refreeze thawed ADSTILADRIN.

Storage and Transfer Guidelines

• ADSTILADRIN vials can be transferred between the refrigerator and room temperature, provided the total storage time does not exceed:
• 24 hours at room temperature
• 7 days in the refrigerator, including thawing time

Preparing ADSTILADRIN for instillation

• https://ferringusa.com/wp-content/uploads/sites/12/2024/08/ADSTILADRIN-USPI-08.2024-CLEAN.pdf — package insert

• https://www.adstiladrin.com/wp-content/uploads/2023/08/Getting_Started_With_ADSTILDARIN-_For_Patients_Downloadable_PDF.pdf — flyer for patients

• https://www.adstiladrinhcp.com

• https://www.adstiladrin.com

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239371/

• https://www.adstiladrinhcp.com/dosing/

• https://www.aetna.com/cpb/medical/data/1000_1099/1024.html

• https://www.adstiladrinhcp.com/resources/

• https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin

• https://medlineplus.gov/druginfo/meds/a623062.html

• https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/adstiladrin

• https://www.va.gov/formularyadvisor/DOC_PDF/CFU_Nadofaragene_firadenovec_ADSTILADRIN_Criteria_Sep_2023.pdf

• Instructions for use: