On May 10, 2021 Hamlet Pharma reported the successful outcome of the dose-escalation study, which is an extension of the Phase I/II trial. Patients with bladder cancer were treated with increasing doses of Alpha1H, following a dose-escalation protocol (Press release, HAMLET Pharma, MAY 10, 2021, View Source;utm_medium=rss&utm_campaign=marked-increase-in-tumor-response-with-higher-doses-of-alpha1h [SID1234579587]). The initial data analysis has revealed a dramatic increase in the tumor response to Alpha1H, measured both as shedding of tumor fragments into the urine and as changes in remaining tumor tissue.
Hamlet Pharma has previously reported the successful completion of the Phase I/II bladder cancer study using a 1.7 mM dose of Alpha1H. We have now performed a dose-escalation study, using 8.5 or 17 mM, i.e. five or ten times higher doses in patients with superficial bladder cancer.
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Alpha1H triggered massive shedding of tumor cells and tumor fragments into patient urine. A dose-dependent increase was demonstrated, resulting in significantly higher shedding than in the first study (P<0.0001). As shown earlier, significant cell shedding did not occur in the placebo group, supporting a treatment effect.
Major effects on tumor tissue were detected by histopathology of tumor biopsies, obtained at surgery after the end of treatment. Tumor fragmentation and shedding of tumor fragments was visible and the remaining tumor showed a loss of viability, with large areas of cells undergoing apoptosis or necrosis.
Apoptosis is a beneficial, non-toxic form of cell death, and a desirable outcome to limit the side effects of cancer therapy. In addition to the apoptotic changes in the tumors, a pronounced apoptotic response was detected in cells and tumor fragments shed by the treated patients, confirming that Alpha1H accelerates cell death in the tumor.
Furthermore, the tumor fragments in urine were shown to contain large amounts of Alpha1H, confirming the efficiency with which the higher doses of Alpha1H reach tumor tissue. The results suggest that uptake of Alpha1H by the tumor triggers apotosis, tumor fragmentation and release of the affected tumor fragments by shedding into the urine.
"The dose-dependent increase in tumor response is dramatic and provides further motivation to develop Alpha1H for therapeutic use in bladder cancer," says Catharina Svanborg, founder and chairman of the board of Hamlet Pharma Ltd.
"The results support our strategy to develop Alpha1H for Phase III trials" says Mats Persson, CEO of Hamlet Pharma Ltd.