FDA Grants RMAT Designation to enGene's Detalimogene for High-Risk Bladder Cancer
enGene Holdings Inc. announced that the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to its lead investigational therapy, det...
Breakthrough Clinical Results
enGene Holdings Inc. announced that the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to its lead investigational therapy, detalimogene voraplasmid (detalimogene), for treating high-risk, BCG-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The RMAT designation accelerates the development and review process. This designation is based on positive preliminary results from the ongoing LEGEND Phase 2 trial, showing clinical activity and favorable tolerability. Detalimogene is a non-viral gene-based immunotherapy designed for streamlined administration in urology clinics, offering a potential transformative option for patients with limited treatment choices.
Key Highlights
- FDA grants RMAT designation to detalimogene for high-risk, BCG-unresponsive NMIBC with CIS.
- RMAT designation accelerates development and review, offering regulatory advantages.
- Positive preliminary results from the LEGEND Phase 2 trial support the designation.
- Detalimogene offers a potentially transformative treatment option for patients with limited choices.
Incidence and Prevalence
Global Bladder Cancer Statistics
Incidence and Prevalence
Bladder cancer ranks as the ninth most common malignancy worldwide according to one source, while another source positions it as the tenth most common cancer in the world.
According to the Global Burden of Disease (GBD) 2019 study, the global prevalence of bladder cancer has increased substantially from 1990 to 2019, reaching 2,869,046.4 cases (95% UI: 2,614,200.3-3,114,474.4) in 2019.
The age-standardized prevalence rate has risen significantly from 20.9 per 100,000 population in 1990 to 37.1 per 100,000 population in 2019, with an Estimated Annual Percentage Change (EAPC) of 1.97 (95% CI: 1.93-2.01).
Another source reports that bladder cancer is associated with over 614,000 new cases annually worldwide.
Mortality and Disease Burden
Bladder cancer accounts for nearly 200,000 deaths worldwide yearly according to one source, while another source reports approximately 220,000 deaths annually.
The global burden of bladder cancer, measured by Disability-Adjusted Life Years (DALYs), increased from 48.0 per 100,000 population in 1990 to 56.8 per 100,000 population in 2019, with an EAPC of 0.47 (95% CI: 0.4-0.53).
United States Statistics
In the United States specifically, one source mentioned that in 2010, approximately 70,000 new cases of bladder carcinoma (52,000 in men and 18,000 in women) and approximately 14,000 deaths were expected.
Survival Rates
The five-year survival rate for bladder urothelial carcinoma (BLCA) is reported to be between 5-70%, with patients having a poor clinical outcome.
For metastatic urothelial carcinoma, the overall survival is between 12 and 15 months, and the 5-year survival is in the range of 5-15%.
Cancer Types
Urothelial carcinoma (UC) constitutes more than 90% of bladder cancer cases according to multiple sources, with some stating it accounts for "nearly 90%" or "more than 90%" of cases.
Regional Variations
The GBD 2019 study demonstrates a significant increase in prevalence, incidence, mortality, and DALYs, with substantial variations across sociodemographic index (SDI) quintiles and GBD regions.
Economic Burden
Economic Burden of Bladder Cancer in USA and Europe
Overview
Bladder cancer is one of the most expensive cancers to manage due to the need for extensive treatment and follow-ups that often involve invasive and costly procedures. It represents a significant global health concern owing to its prevalence, negative impact on quality of life, and high treatment costs.
United States Economic Burden
Medicare Patient Costs
Among 1,873 eligible Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC), the mean cumulative per-patient cost was $82,912 for all patients. These costs increased significantly with additional lines of therapy:
- Untreated patients: $57,207
- First line of therapy (LOT1): $99,213
- Second line of therapy (LOT2): $125,190
- Third or greater line of therapy (LOT3+): $163,884
The mean per patient per month cost was $18,827 for all patients, with costs decreasing as the number of lines of therapy increased: - Untreated: $27,211 - LOT1: $9,601 - LOT2: $7,325 - LOT3+: $6,017
Over 50% of Medicare patients with mUC received no chemotherapy, and among those treated with chemotherapy, most received only one LOT.
Lifetime Costs by Stage
A SEER-Medicare analysis revealed varying mean lifetime costs by cancer stage: - Stage 0: $151,626 - Stage I: $150,123 - Stage II: $149,728 - Stage III: $190,996 (highest lifetime costs) - Stage IV: $117,503
Cost Distribution
- Hospitalizations not involving cystectomy contributed about half of lifetime costs across all stages
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Cystectomy contributed 2-13% of total lifetime costs:
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Stage 0: $3,356
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Stage I: $7,011
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Stage II: $11,855
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Stage III: $25,509
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Stage IV: $11,693
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UC-related office visits contributed 8-15% of lifetime costs:
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Stage 0: $11,717
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Stage I: $14,611
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Stage II: $19,882
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Stage III: $21,480
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Stage IV: $17,820
Cost-Effectiveness of New Treatments
A cost-effectiveness study of pembrolizumab for second-line treatment of advanced urothelial carcinoma found: - Standard-of-care chemotherapy: mean cost of $17,232 and mean effect of 0.43 quality-adjusted life-years - PD-L1 test strategy: incremental cost-effectiveness ratio of $122,933/quality-adjusted life-year - Treating all patients with pembrolizumab: incremental cost-effectiveness ratio of $197,383/quality-adjusted life-year compared to the PD-L1 test strategy
Neither pembrolizumab strategy was cost-effective based on a $100,000/quality-adjusted life-year willingness-to-pay threshold.
European Economic Burden
The introduction of immune checkpoint inhibitors (ICIs) in European guidelines has substantially increased the cost of medications for metastatic urothelial carcinoma (mUC).
A pragmatic approach to assess costs across Europe involved: 1. Collection of costs of recommended medications in the five most populous European countries 2. Conversion of costs into international dollars to account for differences in purchasing power parity 3. Evaluation of cost trends over time 4. Comparison of medication costs to World Health Organization thresholds
Important differences across European countries were observed, with the annual cost of medications being twofold higher in Italy than in France and the UK.
Future Considerations
While new treatments like ICIs improve patient outcomes, they also come with a high price tag that could strain health care budgets. Results suggest that cost-effectiveness studies will be essential in determining the best and most sustainable treatment strategies in the future.
Detalimogene Voraplasmid Clinical Trials Beyond Bladder Cancer
Based on the provided context, there is no information available about detalimogene voraplasmid (CG0070) being trialed for indications other than bladder cancer. The context does not contain any details about:
- Additional oncological or non-oncological indications beyond urothelial bladder carcinoma
- Clinical trial design methodologies for detalimogene voraplasmid
- Intervention protocols or treatment regimens for this therapy
- Phase I, II, or III clinical trials for this treatment in any indication
Without specific information in the provided context, I cannot provide details about other indications or intervention models for detalimogene voraplasmid trials.
