New Data Show Durable Response Following Treatment with ADSTILADRIN® (nadofaragene firadenovec-vncg)

• 36-month follow-up data from the Phase 3 study demonstrate one-quarter of patients with high-risk, BCG-unresponsive NMIBC remained free of high-grade recurrence
• Trial showed a 90% three-year overall survival rate, with more than half of cystectomy-free patients at 36 months
• Follow-up analysis of the Phase 3 study continues with five-year treatment and monitoring

Ferring Pharmaceuticals today announced the presentation of new 36-month follow-up data from the Phase 3 study at the 24^th Annual Meeting of the Society of Urologic Oncology (SUO) demonstrating a sustained durability of response with ADSTILADRIN^® (nadofaragene firadenovec-vncg) in adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1). ADSTILADRIN is the first and only intravesical gene therapy approved by the U.S. Food and Drug Administration (FDA) in this patient population.

“These new data continue to build on the body of evidence supporting the efficacy and safety of ADSTILADRIN, adding to the data on its sustained durable response following treatment,” said Elizabeth Garner, M.D., M.P.H., Chief Scientific Officer, Ferring Pharmaceuticals, U.S. “Patients with BCG-unresponsive NMIBC are at high risk for recurrence and disease progression, which can often lead to bladder removal surgery, or cystectomy. ADSTILADRIN is an innovative therapy that we believe will transform the current standard of care for these patients, providing an effective alternative therapy.”

The new interim data are from a 36-month follow-up analysis from the Phase 3 study, which is ongoing with a planned five-year treatment and monitoring phase. From the outset, patients with NMIBC CIS±Ta/T1 received ADSTILADRIN 75 mL intravesical instillation (3 x 10¹¹ vp) once every three months for up to 12 months (four doses) or until unacceptable toxicity or recurrent high-grade (HG) NMIBC. Patients without evidence of HG recurrence were allowed to continue ADSTILADRIN treatment every three months as part of an ongoing follow-up analysis. Among patients who continued treatment after the 12-month Phase 3 period, 25.5% (14/55 patients) remained HG recurrence-free at 36 months following the start of treatment. The Kaplan-Meier (KM)-estimated probability of duration of complete response (CR) for at least 12, 24 and 36 months was 46.5%, 36.6% and 34.2%, respectively.¹

In the overall CIS±Ta/T1 cohort of participants (N=103), the KM-estimated median (95% confidence interval [CI]) duration of HG recurrence-free survival was six months (3.4, 8.3), with a 30.1% (21.55%, 39.2%) probability of (95% CI) of HG recurrence-free survival for at least 12 months. At 36 months, the KM-estimated cystectomy-free survival (95% CI) was 53.8% (43.3%, 63.1%), and the three-year overall survival was 90.4% (82.3%, 94.9%). Two patients (1.9%) discontinued ADSTILADRIN treatment due to adverse events, while four (3.9%) experienced progression to muscle-invasive disease.¹

“The management of patients with continued high-grade NMIBC after treatment with BCG remains challenging,” said Stephen A. Boorjian M.D., who is the Carl Rosen Professor and David and Anne Luther Chair of the Department of Urology at Mayo Clinic, and was the lead investigator on the ADSTILADRIN clinical trial presented at the conference. “These new ADSTILADRIN data emphasize the importance of obtaining long-term follow up from novel therapies to establish treatment expectations.”

Abstract and Presentation Time:

Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Carcinoma in Situ of the Bladder: 36-Month Follow-Up From a Phase 3 Trial

Poster #164, Thursday, Nov. 30 from 4:15 – 5:15 p.m. EST

About ADSTILADRIN

ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).²

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.³ Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022,⁴ 75% of which present as NMIBC.⁵ In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.³ Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).⁶

INDICATION

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

• Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
• Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.

DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

About Ferring Pharmaceuticals

Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, uro-oncology and in specialty areas within gastroenterology, including microbiome therapeutics, and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464) or visit http://www.ferringusa.com/.

References:

1. Boorjian SA, Narayan VM, Konety BR, et. al. Efficacy of intravesical nadofaragene firadenovec for patients with BCG-unresponsive carcinoma in situ of the bladder: 36-month follow-up from a Phase 3 trial. Presented at 24th Annual Meeting of the Society of Urologic Oncology.
2. ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. https://clinicaltrials.gov/ct2/show/NCT02773849.
3. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17.
4. American Cancer Society. Key Statistics for Bladder Cancer. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Updated January 13,2023. Accessed October 15, 2023.
5. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-41.
6. NCCN Guideline Insights. Bladder Cancer, Version 3.2023. www.nccn.org/patients/guidelines/content/PDF/bladder-patient.pdf. Accessed November 7, 2023.

More information is available at the following:

• Health Care Providers: If you are interested in becoming part of the ADSTILADRIN Early Experience Program, please sign up for updates at ADSTILADRINHCP.com.
• Patients and Consumers: For more information about ADSTILADRIN, please call 1-888-FERRING (888-337-7464), and select option number one.

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