Bladder Cancer Drug Alpha1H Shows Benefit in Phase 2 Trial

An investigational agent called Alpha1H may represent a new option for patients with non-muscle invasive bladder cancer, according to results from a recent phase 2 clinical trial led by Hamlet BioPharma.

The trial found that Alpha1H reduced tumor size and activated the immune system against cancer cells, as well as demonstrated a manageable safety profile. The company has submitted its final clinical report to the U.S. Food and Drug Administration (FDA) to help guide next steps.

“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,” said Dr. Catharina Svanborg, CEO of Hamlet BioPharma, in the news release. “These results mark a major milestone for Hamlet BioPharma and for people with cancer in the urinary bladder.”

Alpha1H Shrinks Tumors in Non-Muscle Invasive Bladder Cancer with Few Side Effects

The trial enrolled patients with non-muscle invasive bladder cancer, a form of the disease that affects the inner lining of the bladder but has not spread into the bladder wall, according to Cancer Research UK’s website, cancerresearchuk.org. Results showed that 80% of tumors responded to Alpha1H treatment. In the high-dose group, tumors shrank by an average of 59%.

The drug works by entering tumor cells and triggering apoptosis, also known as programmed cell death. In addition, Alpha1H caused cancer cells to shed into the urine, allowing doctors to track its effects in real time. Patients who received repeat rounds of treatment continued to benefit, suggesting that Alpha1H may have long-lasting effects when given over multiple treatment cycles.

Advanced RNA sequencing added further insight into the drug’s impact. Researchers found that Alpha1H switched off more than 700 cancer-related genes, including some of the most important drivers of tumor growth such as RAS and GJA1. This mechanism helps explain the therapy’s unique anti-cancer activity.

Moreover, Alpha1H activated the immune system in a way that closely resembles the effects of Bacillus Calmette-Guérin (BCG), the standard bladder cancer treatment.

No serious drug-related side effects were reported during the trial, even at higher doses or with repeated treatments. Local effects were observed, which were comparable with placebo. No systemic or body-wide effects occurred, which supports the idea that Alpha1H works locally in the bladder rather than circulating throughout the body.

Alpha1H for Bladder Cancer: How This Emerging Therapy May Help Patients

Bladder cancer is one of the most common cancers worldwide, with more than 500,000 new cases diagnosed each year. Non-muscle invasive bladder cancer accounts for a large portion of these cases. Current treatment options often involve surgery followed by BCG. However, not all patients respond to BCG, and many relapse after treatment. In addition, chemotherapy and systemic immunotherapy can cause toxic side effects.

Therefore, Alpha1H is aiming to meet this unmet need in treatment. The therapy is given before surgery to shrink tumors and reduce the burden of disease, which could help patients avoid more invasive procedures. Additionally, it avoids many harsh effects because works locally in the bladder.

Hamlet BioPharma has received FDA fast track designation for Alpha1H. This means the drug may move through the regulatory process more quickly, according to U.S. FDA website, fda.gov. The company is preparing for discussions with the FDA regarding the design of a phase 3 trial, the next step needed before potential approval.

If approved, Alpha1H could be used in several different ways: as a neoadjuvant treatment before surgery, as an add-on to standard therapies, or potentially as a standalone treatment, the news release concluded.

References

1. “Hamlet BioPharma Announces the Completion of the Alpha1H Phase 2 Study in Non-Muscle Invasive Bladder Cancer,” by Hamlet Biopharma. News release, Aug 21, 2025.
2. “Non-Muscle Invasive Bladder Cancer Staging,” by Cancer Researdch UK. https://www.cancerresearchuk.org/about-cancer/bladder-cancer/types-stages-grades/non-muscle-invasive
3. “Fast Track,” by U.S. FDA. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track

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