Alpha1H Demonstrates Clinical Benefit in NMIBC

A phase 2 study (NCT03560479) evaluating Alpha1H for the treatment of patients with non–muscle-invasive bladder cancer (NMIBC) met its primary and secondary end points, according to an announcement from Hamlet BioPharma.¹

Final findings from the study revealed that approximately 80% of patients treated with Alpha1H experienced a response, with an average tumor size reduction in the high-dose group of 59%. Additionally, clinical benefit was observed in patients who received a second installation.

The study also demonstrated that Alpha1H reached tumor tissue, triggered tumor cell apoptosis, and led to rapid shedding of tumor cells into the urine. Additionally, Alpha1H led to the downregulation of more than 700 of approximately 800 cancer-related genes, per RNA analysis. Investigators also noted a broad immune response with Alpha1H overlapping with BCG, except responses occurred more rapidly and without lasting adverse effects (AEs) compared with what is historically observed with BCG.

Regarding safety, no serious treatment-related AEs were reported, including at higher dose levels or with repeat dosing. The incidence of mild, local AEs was similar between the Alpha1H and placebo arms. No systemic AEs were observed with Alpha1H, which is consistent with its local mechanism of action.

Data from the final analysis of the study have been submitted to the FDA, and Hamlet BioPharma is coordinating with the regulatory agency on the design of a phase 3 study.

“The final clinical report’s consistent efficacy outcomes and favorable safety profile are highly encouraging. The strength of the data provides compelling evidence of Alpha1H’s potential to become a much-needed proactive treatment option, and we look forward to advancing it in our regulatory discussions,” Catharina Svanborg, MD, PhD, chief executive officer of Hamlet BioPharma, stated in a news release. “We are committed to bringing this innovative therapy to patients as quickly and safely as possible. These results mark a major milestone for Hamlet BioPharma and for people with cancer in the urinary bladder. The study was made possible through close collaboration with leading universities and medical centers, including Lund University, Sweden, Motol University Hospital, Czechia and Linnane Pharma AB, whose combined expertise ensured robust design, execution, and analysis.”

Alpha1H Background and Phase 2 Study Design

Alpha1H is designed to form the Alpha1H complex by binding to oleic acid; in preclinical and animal models, the agent has demonstrated the ability to kill a various cancer cells, including the inhibition of tumor development in a bladder cancer model.²

In the phase 2 study, investigators enrolled patients at least 18 years of age with non-muscle invasive papillary bladder cancer per cystoscopy appearance and were slated to undergo transurethral resection of bladder tumor (TURBT).³ Patients needed retain bladder content for at least 1 hour.

Key exclusion criteria comprised a history of muscle-invasive bladder cancer; a history of NMIBC with an interval shorter than 6 months after previous TURBT; treatment with intravesical BCG or chemotherapy within 12 months of enrollment; any other cancer diagnosis within the last 5 years; acute urinary tract infection; and prior radiotherapy or systemic chemotherapy.

In the main part of the study, patients were randomly assigned to received Alpha1H at 7.4 mg/mL or placebo on days 1, 3, 5, 8, 15 and 22 of a single cycle. During an open-label dose-escalation portion, Alpha1H was also given at daily doses of 37 mg/mL and 74 mg/mL.

Safety, efficacy of cell shedding, and changes in papillary characteristics. Secondary end points included induction of apoptosis, histopathology scoring, and tumor response to Alpha1H by gene expression analysis.¹

References

1. Hamlet BioPharma announces the completion of the Alpha1H phase II study in non-muscle invasive bladder cancer. News release. Hamlet BioPharma. August 21, 2025. Accessed August 21, 2025. https://hamletbiopharma.com/hamlet-biopharma-announces-the-completion-of-the-alpha1h-phase-ii-study-in-non-muscle-invasive-bladder-cancer/
2. Alpha1H. Hamlet BioPharma. Accessed August 21, 2025. https://hamletbiopharma.com/cancer/alpha1h-2/
3. A first-in-human study of alpha1H in patients with non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated August 19, 2020. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT03560479