From Challenge to Change: Addressing Unmet Needs in Bladder Cancer Treatment

Modernizing Treatment for an Overlooked Cancer

While modern advancements in molecular biology have enabled precise and sophisticated targeting of many cancers, these innovations have yet to impact patients with bladder cancer, especially the 75% with Non-Muscle Invasive Bladder Cancer (NMIBC) who face high recurrence rates and inadequate responses to standard-of-care treatment.[1] For the 84,000 patients in the U.S. diagnosed with bladder cancer each year, the most common treatment options are limited to Bacillus Calmette-Guérin (BCG), which relies on weakened tuberculosis bacteria to spur an antitumor immune response, or surgical removal of the entire bladder.^{2 3 4}

Emerging solutions are bringing us closer than ever to tackling these unmet medical needs, enhancing patient outcomes and improving overall quality of life for those with NMIBC. Cretostimogene grenadenorepvec represents a new wave of therapies that harness the best of modern medicine. The investigational therapeutic is specially engineered to target and kill bladder cancer cells as well as stimulate an antitumor response. Cretostimogene works in two important ways. It enters cells through entry points on the surface of the bladder and rapidly divides in bladder cancer cells, forcing the cells to burst, destroying the tumor. The destroyed cells then release signals that selectively trigger the body's own immune system to eliminate many of the remaining bladder cancer cells. This dual mechanism initiates a chain reaction of cancer cell death with potential for durable, complete responses as demonstrated in Phase 2 and ongoing Phase 3 trials.⁵

“You only have one bladder.”

For physicians and patients, cretostimogene grenadenorepvec may be a much-needed advancement in the bladder cancer treatment paradigm that could help thousands of patients avoid surgery. Complete removal of the bladder is a life-changing procedure that often takes an emotional toll through body image concerns, anxiety and depression. Many patients must navigate life with a urine bag and those with neobladders must retrain their body to urinate without the usual sensations or control. ^2 3 4

One patient spoke to their experience, highlighting the all-too-frequent struggles associated with NMIBC treatment:

"Radical cystectomy is a rough surgery and a major life change, it's a rough year of recovery and a big surgery. We need to prevent patients from having to go through this, if we can. You only have one bladder."

- Karen Gross, Bladder Cancer Patient and Patient Advocate, who has supported patients who have undergone cystectomy

The physical and emotional burdens of bladder cancer removal underscore the critical need for innovative solutions that effectively address the disease and prioritize patient safety and long-term outcomes.

The Future of NMBIC Care

Cretostimogene is yielding encouraging results in several bladder cancer studies, including two Phase 3 trials targeting high-risk BCG-unresponsive NMIBC: one for carcinoma in situ (CIS) (BOND-003 Cohort C) and another for papillary-only cases (BOND-003 Cohort P).⁶ Both BOND-003 studies reinforce cretostimogene’s potential best-in-class durability, safety, and efficacy profiles and are supported by compelling numbers from one of the largest and most mature data sets in the space.⁶  Out of the 110 participants in BOND-003 Cohort C, 75.5% showed a complete response (CR) rate at any time. There were no Grade 3 or greater treatment-related adverse events (TRAEs) or deaths reported. Patients who experienced TRAES of any grade had a median resolution time of one day. No treatment-related discontinuation of cretostimogene was observed. 97.3% of patients completed all expected treatments, demonstrating favorable patient adherence and compliance. The most common TRAEs (≥10%) were bladder spasm, pollakiuria, micturition urgency, dysuria, and hematuria. Furthermore, no patients discontinued cretostimogene due to treatment-related issues and 97.3% completed all expected doses, demonstrating strong patient adherence and compliance.⁶ Data from BOND-003 Cohort P demonstrated cretostimogene also has activity and efficacy in BCG-unresponsive patients with Ta/T1 lesions, supporting cretostimogene’s mechanism of action (MOA) across the different types of bladder cancer being studied and its potential as a backbone therapy in bladder cancer.

Cretostimogene is similar to BCG in terms of its intravesical administration and could potentially fit within the current urology office workflow.  An innovative dual MOA positions cretostimogene to potentially work well as either a monotherapy or in combination, by selectively replicating and destroying cancer cells while simultaneously amplifying the immune response against bladder tumors.⁵ Unlike surgical intervention, this approach offers effective disease management without radical, invasive organ removal. The strong safety and efficacy profile of cretostimogene, along with its best-in-class durability, could potentially address an unmet need for NMIBC patients as a potential backbone bladder-sparing therapeutic if approved by the FDA.

Bringing New Meaning to NMIBC: Novel Means of Innovation for Better Care

As research and development continue, great promise exists for the future of NMIBC treatment extending beyond the existing standards of care within the innovation of oncolytic immunotherapies. The focus must remain on delivering solutions that effectively manage the disease and prioritize patients’ quality of life, with the goal of bringing bladder-sparing treatments that provide durable, efficacious, and safe outcomes to patients.