Ferring Testing Bladder Cancer Gene Therapy Adstiladrin’s Mettle in Real-World Setting With ABLE-41 Observational Study

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In anticipation of Bladder Cancer Awareness Month, CGTLive® has decided to take a closer look at this noninterventional real-world study.

Ferring Pharmaceuticals’ nadofaragene firadenovec (Adstiladrin), a marketed adeno-associated virus (AAV) vector-based gene therapy currently approved for the treatment of adult patients with high-risk, Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors, is currently being evaluated in the phase 4 observational study ABLE-41 (NCT06026332).1 In anticipation of Bladder Cancer Awareness Month, which is observed annually in May by the patient and clinician communities, CGTLive® has decided to take a closer look at this noninterventional real-world study.

ABLE-41 was launched on September 15, 2023, and is intended to provide information about experiences, outcomes, and usage patterns for patients treated with Adstiladrin in the commercial setting in the United States. According to the clinicaltrials.gov page, the multicenter study is expected to enroll approximately 800 patients who have been prescribed and scheduled to be treated with the gene therapy at participating treatment centers. Patients who received their first dose of Adstiladrin after September 5, 2023, at a nonparticipating treatment center may also be eligible if their center later becomes an active study site for ABLE-41. In a poster presented by Ferring at the 20th Annual ASCO Genitourinary Cancers Symposium, held January 25-27, 2024, in San Francisco, CA, the company noted that it expects to enroll 200 patients in ABLE-41 over 16 months, based on monthly recruitment rates from a previous US trial and the number of centers expected to be part of the study.2

“ABLE-41 is a unique real-world registry that will provide important evidence on what patients and physicians can expect from intravesical gene therapy in a clinical setting,” Siamek Daneshmand, MD, who is affiliated with USC/Norris Comprehensive Cancer Center and the University of Southern California, and a lead ABLE-41 investigator, said in a January 2024 statement.1 “I am thrilled to be part of this ongoing research and among the first uro-oncologists to be treating patients with Adstiladrin in a clinical setting. This is an innovative therapy that is already changing how we manage NMIBC patients who no longer respond to standard BCG therapy, providing an alternative to radical cystectomy, or bladder removal surgery.”

According to the clinicaltrials.gov page, which was most recently updated on April 26, 2024, ABLE-41 is currently recruiting participants at sites in Arkansas, California, Florida, Indiana, Kansas, Minnesota, New York, Ohio, South Carolina, Tennessee, and Virginia. Patients in ABLE-41 will be followed for 24 months, barring discontinuation or withdrawal from participation. The study has an estimated completion date of December 31, 2025.

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ABLE-41's 2 primary end points include whether or not patients with CIS, with or without concomitant high-grade Ta or T1 papillary disease, are able to achieve a complete response (CR) at their first evaluation, which takes place 3 months after the first instillation of the gene therapy, and whether or not they are able to achieve a CR at any time within 1 year from the first instillation. Among the study’s key secondary end points are the duration of CR/cysectomy-free survival, high-grade recurrence-free survival, progression-free survival, overall survival, and bladder cancer-specific mortality.2 Safety is also a key secondary end point and will be measured by the type, incidence, relatedness to Adstiladrin, severity grading, and seriousness of adverse events that occur during the study. Severity grading will be conducted via National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. Additional end points include prior treatments and outcomes before starting treatment with Adstiladrin; the number of Adstiladrin instillations and time intervals between instillations; reasons patients discontinue treatment with Adstiladrin; concomitant therapies for bladder cancer and major comorbidities in the patients; occurrences of retreatment of patients who do not respond to Adstiladrin at 3 months or when deemed appropriate by the treating physician; any subsequent line of therapy received by participants after they discontinue Adstiladrin; results from a customized patient experience survey for patients and the Work Productivity and Activity Impairment questionnaire as adapted for caregiving for caregivers that will each take place before each instillation of Adstiladrin that a participant receives; results of a customized physician survey that will take place at 1 month following the first patient’s first instillation or as soon as possible upon site activation and at 12 and 24 months after the first patient’s first instillation; and the proportion of patients with prespecified biomarker tested in the routine care setting, with timing, type of sampling, and laboratory results.

The study population will consist of patients who have been prescribed Adstiladrin at participating sites who have signed and dated an informed consent form (ICF); the ICF signing must have taken place when the patient was 18 years of age or older. Patients who are currently enrolled in any clinical trial, those who were previously treated with Adstiladrin in a clinical trial, and those who are pregnant or breastfeeding will be excluded from participation in ABLE-41.

Ferring announced that the first patient, a 78-year-old man, had been treated with Adstiladrin in the commercial setting as part of an Early Experience Program in September 2023.3 Notably, the patient, who received treatment at a center in the midwest region, was also the first patient to be enrolled in ABLE-41.

Adstiladrin was originally approved by the FDA for its current indication in December 2022.4 The therapy, a nonreplicating adenoviral vector-based gene therapy, is administered intravesically every 3 months.

“High risk NMIBC patients who don’t respond to BCG therapy are at risk for recurrence and progression and the preferred treatment has historically been radical cystectomy (surgical removal of the bladder). Developing a convenient, locally delivered, effective, bladder preserving option such as Adstiladrin has long been needed,” Daniel Shoskes, MD, vice president, medical director- uro-oncology, at Ferring Pharmaceuticals and emeritus professor of urology at the Cleveland Clinic, said in a statement issued to CGTLive. “With this new post-marketing registry we are looking to build an additional body of data with real world evidence.”

REFERENCES
1. Phase 4 study evaluating use of Adstiladrin® (nadofaragene firadenovec-vncg) in real-world setting. News release. Ferring Pharmaceuticals. January 24, 2024. Accessed April 29, 2024. https://ferringusa.com/?press=phase-4-study-evaluating-use-of-adstiladrin-nadofaragene-firadenovec-vncg-in-real-world-setting
2. Daneshmand S, Shore N, Scholz K, et al. ABLE-41: Nadofaragene firadenovec-vncg early utilization and outcomes in a real-world setting in the United States. Presented at: the 20th Annual ASCO Genitourinary Cancers Symposium, held January 25-27, 2024, in San Francisco, CA. Abstract #TPS705
3. First bladder cancer patient dosed with commercially available intravesical gene therapy Adstiladrin® (nadofaragene firadenovec-vncg). News release. Ferring Pharmaceuticals. September 12, 2024. Accessed April 29, 2024. https://ferringusa.com/?press=first-bladder-cancer-patient-dosed-with-commercially-available-intravesical-gene-therapy-adstiladrin-nadofaragene-firadenovec-vncg
4. FDA Approves First Gene Therapy for the Treatment of High-Risk, Non-Muscle-Invasive Bladder Cancer. News release. FDA. December 16, 2022. Accessed April 29, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-high-risk-non-muscle-invasive-bladder-cancer
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