PUBLISHER: DelveInsight | PRODUCT CODE: 1553401
PUBLISHER: DelveInsight | PRODUCT CODE: 1553401
DelveInsight's "Non-muscle Invasive Bladder Cancer-Market Insights, Epidemiology, and Market Forecast-2034" report delivers an in-depth understanding of Non-muscle invasive bladder cancer, its historical and forecasted epidemiology, and its market trends in the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
The non-muscle invasive bladder cancer market report provides current treatment practices, emerging drugs, non-muscle invasive bladder cancer market share of the individual therapies, and current and forecasted non-muscle invasive bladder cancer market size from 2020 to 2034, segmented by seven major markets. The report also covers current non-muscle invasive bladder cancer treatment practices/algorithms and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.
Study Period: 2020-2034
Non-muscle Invasive Bladder Cancer Overview
Non-muscle-invasive bladder cancer represents a category of bladder cancer where the tumor is confined to the innermost layer of the bladder lining without invading the muscle. This early-stage form accounts for a significant proportion of bladder cancer cases. NMIBC is often characterized by superficial tumor growth and typically presents with papillary tumors or carcinoma in situ. Due to its propensity for recurrence and progression, NMIBC requires vigilant management involving transurethral resection of the tumor (TURBT) and subsequent intravesical therapies like BCG immunotherapy or chemotherapy. Surveillance through regular cystoscopies and adherence to guidelines are essential to monitor and manage this condition effectively.
Non-muscle Invasive Bladder Cancer Diagnosis
The diagnosis of NMIBC relies upon cystoscopy and tissue sampling. Initial cystoscopic evaluation is often performed in the office setting with or without biopsies of visualized tumors. Flexible cystoscopy in conjunction with topical intraurethral anesthetic lubricant decreases patient discomfort during the procedure, particularly in men. Most cases of NMIBC are initially treated with transurethral resection, but careful cystoscopic examination of the entire urethra and bladder should precede resection. However, surgeons may proceed directly to TURBT should CT or MRI reveal a bladder lesion during the evaluation of hematuria. During resection, tumors of significant size should be resected and labeled. The anatomic location of tumors with respect to the bladder neck and ureteral orifices, tumor configuration (papillary or sessile), as well as both the size and number of tumors should be documented in some consistent manner (e.g., diagram, text description) to inform future follow-up and evaluate treatment response.
Further details related to diagnosis will be provided in the report...
Non-muscle Invasive Bladder Cancer Treatment
High-risk NMIBC is a prevalent form of bladder cancer; although less severe than its muscle-invasive counterpart, it can display significant aggressiveness. Treatment options encompass careful observation with regular cystoscopies, intravesical immunotherapy involving the administration of BCG into the bladder, and, in more extreme cases, surgical removal of the bladder (cystectomy). Despite favorable recovery prospects, managing this cancer often involves intensive treatment and prolonged observation over several years. The primary interventions for cases confined to the bladder's inner lining include surgery, intravesical immunotherapy with BCG, and intravesical chemotherapy. Surgery, either as a standalone procedure or in combination with other modalities, is commonly employed. TURBT, a surgical approach, is frequently performed to remove visible cancer cells, ensuring comprehensive management.
Further details related to treatment will be provided in the report....
The Non-muscle invasive bladder cancer (NMIBC) epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by the total number of prevalent cases of NMIBC, stage-specific cases of NMIBC, grade-specific cases of NMIBC, risk-specific cases of NMIBC, and age-specific cases of NMIBC in the 7MM market covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.
The drug chapter segment of the non-muscle invasive bladder cancer report encloses a detailed analysis of the late mid-stage (Phase III and Phase II) pipeline drug. The current key players include Ferring Pharmaceuticals/FKD Therapies Oy (ADSTILADRIN), Merck Sharp & Dohme (KEYTRUDA), ImmunityBio (ANKTIVA), and others. The drug chapter also helps understand the details of the Non-muscle invasive bladder cancer clinical trial details, expressive pharmacological action, agreements and collaborations, approval, and patent details, and the latest news and press releases.
Marketed Drugs
ADSTILADRIN (nadofaragene firadenovec): Ferring Pharmaceuticals/FKD Therapies Oy
ADSTILADRIN is a gene therapy developed as a treatment for adult patients with BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder once every three months. The drug is classified as an Advanced Therapy Medicinal Product (ATMP) by the European Medicines Agency. In December 2022, Ferring Pharmaceuticals announced that the US FDA approved ADSTILADRIN for the treatment of adult patients with high-risk, BCG unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. In April 2024, Ferring Pharmaceuticals and SK Pharmteco announced an agreement to scale up commercial manufacturing capacity for the drug substance of Ferring's intravesical gene therapy ADSTILADRIN to ensure long-term future supply.
ANKTIVA (nogapendekin alfa inbakicept-pmln): ImmunityBio
ANKTIVA is a novel IL-15 superagonist complex with an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor a/IgG1 Fc fusion protein. In April 2024, the US FDA approved ANKTIVA plus BCG for the treatment of patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumors. The drug is currently being evaluated in adult patients in two clinical NMIBC trials. QUILT-3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC CIS and Papillary Disease; QUILT-2.005 is investigating the use of N-803 in combination with BCG for patients with BCG-naive NMIBC. As per ImmunityBio corporate presentation 2024, the company has planned to explore ANKTIVA + iBCG (recombinant BCG) for BCG Replacement NMIBC. This study will be in collaboration with the Serum Institute of India and ImmunityBio.
Emerging Drugs
CG0070 (cretostimogene grenadenorepvec): CG Oncology
CG0070, a selectively replicative oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective Rb pathway. Monotherapy activity of cretostimogene grenadenorepvec in NMIBC after BCG failure has been established in two past studies of cretostimogene grenadenorepvec, V0046 and BOND-002. Studies of cretostimogene grenadenorepvec alone (Phase III BOND-003, ongoing study) will further elucidate the potential role of cretostimogene grenadenorepvec-based therapy for BCG-unresponsive NMIBC. The company presented updated results from BOND-003 Cohort C at the American Urological Association (AUA) 2024 annual meeting. CG0070 is also investigated in a clinical collaboration with Merck to evaluate the combination of CG0070 with the anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in a Phase II CORE-001 clinical study for the treatment of high-grade NMIBC in the BCG-unresponsive patient population. CG Oncology presented positive final results from this study at the ASCO 2024 annual meeting. The company believes that these results support further investigation of cretostimogene in combination with checkpoint inhibitors, and they plan to incorporate these findings into another planned CORE-008 trial in high-risk NMIBC.
Sasanlimab (PF-06801591): Pfizer
Sasanlimab is an anti-PD-1 treatment. It blocks the PD-1 protein on the surface of immune T-cells that can attack healthy cells. PD-1 is an immune checkpoint protein that prevents T-cells from attacking healthy cells. The drug is being evaluated in a Phase III study with BCG (BCG induction with or without BCG maintenance) versus BCG (induction and maintenance) in participants with high-risk, BCG-naive NMIBC. In August 2022, the Sponsor announced the discontinuation of enrollment to Part B, which enrolled participants with BCG unresponsive NMIBC. The decision to discontinue enrollment in Part B was not made for safety reasons. The company anticipated data readout from the Phase III trial of sasanlimab in NMIBC in the first half of 2025.
Drug Class Insight
Currently, BCG is the leading standard of care in the NMIBC setting. In the emerging pipeline, checkpoint inhibitors (KEYTRUDA), gene therapy (ADSTILADRIN), cell therapy (TARA-002), oncolytic Immunotherapy (Lerapolturev, CG0070, and others), virus-like drug conjugate (belzupacap sarotalocan), photodynamic compound (Ruvidar), and others are different classes that are showing positive results in NMIBC patients. Checkpoint inhibitors and gene therapy are already approved in the BCG unresponsive NMIBC patient pool.
Immune checkpoint inhibitors (ICIs)
Immune checkpoint inhibitors (ICIs) are a powerful tool in cancer immunotherapy, designed to enhance the body's natural defenses against cancer cells. KEYTRUDA, approved in 2020 for BCG-unresponsive patients, has demonstrated significant efficacy in this population. The emerging pipeline includes several PD-(L)1 inhibitors in Phase III trials, such as TECENTRIQ, IMFINZI, and sasanlimab, all being evaluated in combination with BCG for BCG-naive patients. However, results for these inhibitors in BCG-naive patients are not yet available. It will be interesting to observe the efficacy and safety outcomes in this group and how their approval could alleviate the treatment burden for naive patients, especially in the context of a BCG shortage. The lack of response in many cancer patients to immune checkpoint inhibitors highlights the significant clinical need to develop new therapies suitable for both immune checkpoint-naive and -refractory patients.
Interleukin-15 receptor superagonist
The most recent therapy approved by the FDA is ANKTIVA + BCG developed by ImmunityBio. Notably, in NMIBC patients, the complete response rate (CRR) reached 62%, with a median duration of response not reached (0.0, 47.0+). Around 58% and 40% of patients reached a duration of response (DoR) of =12 and =24 months, respectively. In terms of safety, permanent discontinuation of ANKTIVA with BCG due to adverse reactions occurred in 7% of patients. The efficacy of ANKTIVA is better than other approved drugs, but in terms of safety it is not better than ADSTILADRIN. ANKTIVA does not require any special freezers or equipment; it can be stored in standard refrigerators and freezers. Since ANKTIVA is administered as a mixture with BCG, it does not ''necessitate any different equipment or processing from BCG administration. This means urology practices do not need to make any changes to order, store, or implement ANKTIVA. This ease of integration could lead to a rapid adoption of ANKTIVA in clinical settings.
Oncolytic Immunotherapy
Currently, no oncolytic immunotherapy is approved for NMIBC patients, but companies are exploring drugs for intermediate and high-risk NMIBC patients. A key drug in this class is CG0070, which has a unique mechanism that may synergize with PD-1 inhibitors. Notably, 75.2% of patients evaluated for efficacy achieved a complete response at any time. The company is conducting another Phase II trial of CG0070 in combination with pembrolizumab. The CRR in the intent-to-treat (ITT) population at 24 months was 54%. Among patients who achieved a CRR at 12 months, 95% maintained this response for another 12 months, with the median DoR exceeding 21 months and still needs to be reached. This combination aims to enhance overall treatment efficacy by leveraging synergistic effects, potentially improving outcomes for BCG-unresponsive high-grade NMIBC patients. After approval, CG0070 is expected to compete with ADSTILADRIN and EG-70.
NMIBC remains a very challenging disease to treat, with high rates of recurrence and progression associated with current therapies. The high rates of progression and recurrence with current therapies for NMIBC necessitate lifelong active surveillance, making bladder cancer the most expensive cancer to treat from diagnosis to death, as well as driving the need for the development of new therapies in patients with NMIBC.
The current treatment regimen includes surgery, intravesical immunotherapy (BCG), and intravesical chemotherapy. Intermediate- or high-risk NMIBC is generally treated with TURBT, followed by adjuvant BCG immunotherapy, which is the gold standard treatment for reducing tumor recurrence rates and preventing subsequent stage progression. Stage 0 bladder cancer is most often treated with TURBT with fulguration followed by intravesical therapy within 24 h. Sometimes, no further treatment is needed. Cystoscopy is then done every 3-6 months to watch for signs that cancer has come back.
In addition, the FDA has approved only three drugs for the treatment of NMIBC: KEYTRUDA and ADSTILADRIN, which were approved in 2020 and 2022, respectively, and the latest addition, ANKTIVA, which the FDA approved in April 2024. All three are approved in the US only.
The landscape of managing BCG-unresponsive NMIBC patients in real-world clinical practice reveals significant trends. Approximately a quarter of physicians' NMIBC caseload comprised BCG-unresponsive patients for whom BCG therapy was no longer a viable option. Furthermore, about a third of the NMIBC patient caseload had not undergone BCG therapy, possibly due to pending treatment post-TURBT. The global scarcity of BCG has exacerbated these challenges, limiting adequate induction and maintenance therapies and resulting in higher recurrence and failure rates.
NMIBC pipeline possesses potential drugs in mid and late-stage developments for low and high-risk NMIBC to be launched in the near future. The major drugs in the pipeline for high-risk NMIBC include CG0070 (CG Oncology), Sasanlimab (Pfizer), EG-70 (enGene), UGN-102, and UGN-103 (Urogen), Ruvidar (Theralase), TAR-210 and TAR-200 (Johnson & Johnson), and others. Also, these emerging therapies are expected to launch during the forecast period [2024-2034].
This evolving landscape showcases the challenges and shifting paradigms in managing BCG-unresponsive NMIBC patients, emphasizing the need for further research, personalized treatment strategies, and broader adoption of biomarker-driven approaches for improved patient outcomes.
Detailed market assessment will be provided in the final report.
Key Findings
This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2024-2034. The landscape of NMIBC treatment has experienced a profound transformation with the uptake of novel drugs. These innovative therapies are redefining standards of care. Furthermore, the increased uptake of these transformative drugs is a testament to the unwavering dedication of physicians, oncology professionals, and the entire healthcare community in their tireless pursuit of advancing cancer care. This momentous shift in treatment paradigms is a testament to the power of research, collaboration, and human resilience.
CG0070, developed by CG Oncology, has demonstrated significantly better efficacy compared to approved drugs for BCG-unresponsive NMIBC, achieving around a 75% CRR in these patients. Additionally, the drug has shown impressive results when used in combination with immunotherapy, with 95% of patients who achieved CRR at 12 months maintaining it for another 12 months. The median DoR has yet to be reached but exceeds 21 months. We have anticipated a launch by 2026; this drug could capture a billion-dollar market by 2034 following its approval.
Non-muscle Invasive Bladder Cancer Pipeline Development Activities
The report provides insights into therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics. Companies like Roche, Pfizer, AstraZeneca, UroGen Pharma, CG Oncology, Theralase Technologies, enGene, Protara Therapeutics, and others actively engage in mid and late-stage research and development efforts for non-muscle invasive bladder cancer. The pipeline of non-muscle invasive bladder cancer possesses few potential drugs. However, there is a positive outlook for the therapeutics market, with expectations of growth during the forecast period (2024-2034).
Pipeline Development Activities
The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for non-muscle invasive bladder cancer emerging therapy.
KOL- Views
To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the non-muscle invasive bladder cancer evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including oncologists, radiation oncologists, surgical oncologists, and others.
DelveInsight's analysts connected with 30+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as the Institute for Personalized Cancer Therapy, Urologist Cancer Center, University, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or non-muscle invasive bladder cancer market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.
Qualitative Analysis
We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of gaps in disease diagnosis, patient awareness, physician acceptability, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided.
Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.
In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in event-free survival, one of the most crucial primary outcome measures is event-free survival and overall survival.
Further, the therapies' safety is evaluated, wherein the acceptability, tolerability, and adverse events are majorly observed, and this clearly explains the drug's side effects in the trials. In addition, the scoring is also based on the probability of success and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.
Market Access and Reimbursement
NMIBC is a costly disease to manage, with higher healthcare costs associated with an increased risk of disease progression. There is a high unmet need for safe and effective treatments that reduce the risk of disease progression and provide symptomatic relief and HRQoL improvements for patients.
The Merck Access Program is designed to provide patients with reimbursement and insurance coverage-related information throughout their treatment process. The program helps with benefit investigations, billing and coding, copay assistance for eligible patients, prior authorizations and appeals, and referral to the Merck Patient Assistance Program for eligibility determination.
The representative medical expenses based on the Japanese health insurance system are as follows: one cystoscopy costs 9500 Japanese yen (equivalent to USD 67 as of July 2023), a single dose of BCG Tokyo 172 strain costs approximately 14,000 yen (USD 98), and one hospitalization for TURBT costs 400,000 yen (USD 2,821).
Detailed market access and reimbursement assessment will be provided in the final report.