Bacillus Calmette-Guerin(ImmunityBio)

Pfizer has announced that a phase 3 study evaluating its investigational anti-PD-1 monoclonal antibody sasanlimab in a subset of bladder cancer patients met the primary endpoint of event-free survival. The phase 3 CREST trial has been assessing the subcutaneously-administered drug in combination with standard-of-care Bacillus Calmette-Guérin (BCG) as an induction therapy, with or without maintenance, in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). Results demonstrated a 32% reduction in the risk of disease-related events, including high-grade disease recurrence or progression, with the sasanlimab combination compared to BCG treatment alone. The probability of being event-free at 36 months was 82.1% with the sasanlimab combination (induction and maintenance), compared to 74.8% with BCG alone (induction and maintenance), Pfizer said. The company added that sasanlimab plus BCG (induction only) did not extend event-free survival compared to BCG alone (induction and maintenance), a key secondary endpoint in the study, “underscoring the need for BCG maintenance not only as a component of standard-of-care treatment but also in combination with sasanlimab”. Bladder cancer is the ninth most common cancer globally and NMIBC, in which the cancer cells are confined to the inner lining of the bladder, accounts for approximately 75% of all cases. Despite treatment with BCG, up to 50% of high-risk NMIBC patients experience disease recurrence and often require a radical cystectomy, which is associated with significant risks. Megan O’Meara, interim chief development officer, Pfizer Oncology, said the findings from CREST “offer a much-needed therapeutic breakthrough and spotlight sasanlimab as the first immunotherapy combination with BCG to significantly improve outcomes for patients with BCG-naïve, high-risk NMIBC in over three decade”. Results have now been shared with global health authorities to support potential regulatory filings, the company outlined. “We look forward to working with global regulatory authorities to potentially bring sasanlimab as an important new treatment option to patients with high-risk NMIBC,” O’Meara said. The announcement comes just days after Pfizer’s Hympavzi (marstacimab) was approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) to treat haemophilia A or B in adult and paediatric patients.

PRINCETON, NJ, USA I April 26, 2025 I UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, today announced encouraging safety data from the Phase 1 dose-escalation study for UGN-301 (zalifrelimab) intravesical solution, an investigational drug in development for the treatment of recurrent non-muscle invasive bladder cancer (NMIBC). “The early safety profile and clinical activity results from this study are encouraging,” said Jay Raman, M.D., Professor and Chair of Urology, and Professor of Surgery, Penn State Cancer Institute, PA. “This innovative approach of localized drug delivery combined with immune modulation merits additional investigation in the treatment of non-muscle invasive bladder cancer.” The multi-part clinical study included up to 30 patients per arm, aimed to assess safety and determine the recommended Phase 2 dose of UGN-301 as monotherapy and in combination with other agents. In the monotherapy arm, dose escalation continued to the maximum feasible dose. No dose-limiting toxicities and no treatment-emergent adverse events leading to treatment discontinuation were observed. This study also demonstrated that local delivery of UGN-301 formulated in our proprietary reverse thermal gel ( RTGel ® ) allowed sustained exposure of zalifrelimab in the bladder with limited systemic exposure, which mitigated the risk of systemic immune-related toxicities associated with CTLA-4 inhibition. With respect to clinical activity observed in the trial, among evaluable patients who received UGN-301, 46% (6 of 13) of those with Ta/T1 disease and 33% (2 of 6) of those with carcinoma in situ (CIS) ± Ta/T1 disease were recurrence-free or had achieved a complete response at week 12. Notably, 60% (3 of 5) of patients with Ta/T1 disease treated with 300 mg continued to remain recurrence-free at the 15-month disease assessment, including one patient with high-grade T1 disease. In the 500 mg cohort, 25% (1 of 4) of patients with CIS disease and 33% (1 of 3) of patients with Ta/T1 disease remained disease-free at six months, both of whom are still active participants in the study. These findings highlight the potential of UGN-301 as a targeted treatment for NMIBC with an acceptable safety profile. Presentation of data from the combination arms is planned for later this year. “Our hypothesis is that UGN-301’s unique formulation could potentially offer the dual benefits of maximizing therapeutic activity while minimizing systemic side effects, a key challenge in cancer immunotherapy,” said Mark Schoenberg, Chief Medical Officer, UroGen. “Although this requires additional clinical investigation, we are encouraged by the potential of UGN-301 as an investigational treatment for patients with recurrent NMIBC.” About Non-Muscle Invasive Bladder Cancer and High-Grade Disease In the U.S., bladder cancer is the second most common urologic cancer in men. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a serious and potentially life-threatening form of bladder cancer that remains confined to the inner layers of the bladder wall but exhibits aggressive behavior and a higher risk of progression. In the U.S., HG-NMIBC accounts for approximately 30–40% of all newly diagnosed NMIBC cases. Patients with HG-NMIBC face a significantly elevated risk of recurrence and progression to muscle-invasive disease, necessitating close surveillance and aggressive treatment. The standard of care includes complete transurethral resection of bladder tumor, often followed by intravesical therapy such as Bacillus Calmette-Guérin (BCG). However, BCG has a treatment failure rate of approximately 40-50%, leaving patients with limited treatment options short of radical cystectomy. Given the high recurrence and progression rates, HG-NMIBC presents a substantial clinical and quality-of-life burden. Upon recurrence, which occurs in approximately 70% of patients, the patients undergo another round of BCG therapy with a response rate of approximately 30%. About UGN-301 UGN-301 is an anti-CTLA-4 monoclonal antibody (zalifrelimab), originally licensed from Agenus Inc. in 2019. It is formulated with RTGel , our proprietary reverse-thermal hydrogel, for intravesical administration into the bladder. Intravesical administration of UGN-301 is designed to increase drug concentrations in the bladder without significant systemic exposure, potentially diminishing the systemic toxicity associated with CTLA-4 blockade. UroGen is evaluating UGN-301 in a multi-arm Phase 1 study of UGN-301 as monotherapy and in combination with other agents. The safety of UGN-301 is being evaluated in the monotherapy arm of the study as combination therapy for HG-NMIBC. About UroGen Pharma Ltd. UroGen is a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better options. UroGen has developed RTGel reverse-thermal hydrogel, a proprietary sustained-release, hydrogel-based platform technology that has the potential to improve the therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. Our first product to treat low-grade upper tract urothelial cancer and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with low-grade intermediate risk NMIBC are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. Visit www.UroGen.com to learn more or follow us on X (Twitter), @UroGenPharma. SOURCE: UroGen Pharma