Efficacy and Safety of Alpha1H Unveiled in Final Phase 2 NMIBC Report

A final clinical report details the successful completion of a phase 2 study (NCT03560479) of Alpha1H, a novel protein-lipid complex, for the treatment of non–muscle-invasive bladder cancer (NMIBC). The results, which have been submitted to the US FDA, demonstrated that the investigational drug met all primary and secondary end points for both safety and efficacy, positioning it as a potential neoadjuvant therapy for a patient population with significant unmet needs.

Notably, from the report, 80% of tumors responded to Alpha1H with a 59% average tumor size reduction in the high-dose group. Alpha1H was shown to reach tumor tissue, trigger tumor cell apoptosis, and cause rapid shedding of tumor cells into the urine. These treatment effects were durable across repeated cycles, with patients who received a second round of instillations maintaining clinical benefit. Further, the safety profile was confirmed over a longer follow-up with no serious adverse effects observed.

“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. 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,” said Catharina Svanborg, MD, PhD and CEO Hamlet BioPharma, in a press release.

With the successful completion of the phase 2a study, Hamlet BioPharma is in dialogue with the FDA to advance Alpha1H toward a pivotal Phase III trial. The drug has already received FDA fast track designation, underscoring its potential to address a serious condition with an unmet medical need.

About the Phase 2 Study of Alpha1H in NMIBC

The phase 2 study was to evaluate the tolerability and preliminary antitumor effect of Alpha1H in patients with NMIBC awaiting TURBT.² The primary end points are safety, efficacy of cell shedding, change from baseline in characteristics of papillary tumors.

Patients were randomized to receive Alpha1H at 7.4 mg/mL, 37 mg/mL, or 74 mg/mL or placebo. To participate in the study, patients were required to be able to keep the content of the bladder for at least 1 hour, and women of childbearing potential needed to have a negative pregnancy test and use appropriate methods of contraception. Those with a previous history of muscle-invasive bladder cancer, who received Bacillus Calmette-Guérin within the last 12 months, who received intravesical chemotherapy in the last 12 months, with another cancer diagnosis in the past 5 years, or who received prior radiotherapy or systemic chemotherapy were not eligible for participation in the study.

FAQs

What is Alpha1H and what is its primary purpose?

Alpha1H is a drug candidate developed by Hamlet BioPharma that is designed to treat non–muscle-invasive bladder cancer (NMIBC). Its primary purpose is to selectively kill tumor cells and activate the body's immune response to reduce tumor burden in patients.

What were the key findings from the phase 2 clinical trial of Alpha1H?

The phase 2 clinical trial of Alpha1H demonstrated significant efficacy and a strong safety profile. Key findings included an 80% tumor response rate with a 59% average tumor size reduction in the high-dose group, induction of tumor cell apoptosis and shedding into urine, durable effects over repeated treatment cycles, activation of a rapid immune response similar to BCG (Bacillus Calmette-Guérin) but without lasting side effects, and downregulation of over 700 cancer-related genes. No serious drug-related adverse events were reported.

How does Alpha1H's mechanism of action differ from current treatments like BCG?

Alpha1H works by entering tumor cells and causing programmed cell death, while also activating the body's immune response. Unlike BCG, which is an attenuated form of bacteria that stimulates a broad immune response, Alpha1H is a synthetic compound that acts locally in the bladder without systemic exposure. Alpha1H also triggers an immune response more rapidly and without the supply issues or lasting side effects associated with BCG.

What are the potential clinical benefits of Alpha1H for patients with NMIBC?

Alpha1H offers several potential clinical benefits. It can be used as a neoadjuvant treatment to reduce tumor burden, potentially leading to less invasive procedures and improved outcomes. It achieves these effects without the toxic side effects of chemotherapy or systemic immunotherapy. Its strong safety profile, even with repeated dosing, makes it a promising option for patients who do not respond to or relapse after other interventions.

This article was created with assistance from Google Gemini and NotebookLM. The content has been reviewed and edited by Targeted Oncology editors. For more information on the extent and nature of AI usage, please contact us.

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://tinyurl.com/4bf2pdpy

2. 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. http://clinicaltrials.gov/study/NCT03560479