Newsletter 2020 – Issue 1; Bladder Cancer
“Bladder cancer (BC) has the highest lifetime treatment costs per patient (pp) of all cancers, followed by colorectal-, breast-, prostate-, and lung cancer“. Early stage bladder cancer, also known as non-muscle-invasive bladder cancer (NMIBC), represents 70% of new bladder cancer diagnoses and affects 1.6 million patients in Europe (treatment costs are more than €4.9 billion annually. Current NMIBC treatments (surgery, chemotherapy, immunotherapy) are suboptimal: they have significant side-effects and limited efficacy, resulting in a high tumour recurrence rate (approximately 70%). Therefore we are very excited and proud to announce significant progress made and milestones achieved, in the development of Alpha 1H as a new drug candidate for this patient group.
The Phase I/II study
An important clinical milestone was reached in July 2019, when positive effects of Alpha1H were demonstrated in a Phase I/II, placebo-controlled, double blind study in patients with bladder cancer. Data from the clinical study has now been compiled into a publication, which will be submitted shortly. The analyses include all available clinical data, third party evaluations of the patient outcomes, advanced laboratory technology to determine effects on tissues, genes and proteins and careful analyses of population variables.
The positive outcome of the clinical study strengthens HAMLET Pharma’s strategy to develop Alpha1H as a new stand-alone treatment in patients with bladder cancer. This process includes dose-finding studies as well as future trials in larger patient populations.
Dose escalation study
Dose-finding studies are an important step in the drug development process, to define the most suitable and efficient dose for future clinical studies. Hamlet Pharma is therefore extending the clinical trial program to include a dose escalation step and the Czech authority SUKL, has approved dose-escalation as an extension of the ongoing study.
The necessary and technically challenging production of substance for higher doses of Alpha1H and the formulation for the dose escalation study are now complete, and the final quality controls are ongoing to ensure compliance with current guidelines. In addition, the clinic in Prague has been initiated and is ready to include patients, as soon as the study medication is released.
Combination treatment using Alpha1H in conjunction with chemotherapy
Alpha1H shows significant promise as a new and effective cancer drug with low toxicity, and is under active development as a stand-alone drug candidate. In addition, a new pre-clinical discovery shows that Alpha1H improves the therapeutic efficacy of conventional cancer drugs. In animal models of bladder cancer, Alpha1H caused a dramatic increase in treatment efficacy of the chemotherapeutic agents such as Epirubicin or Mytomycin C, which are widely used for intravesical chemotherapy of new and frequently recurring cancers. The findings suggest that that in addition to acting as a cancer drug on its own, Alpha1H may be used in combination with conventional cancer drugs to further improve their effect at lower, less toxic levels.
These new findings widen the potential to use Alpha1H in bladder cancer and other cancer indications. Combination therapy is widely used in cancer patients, to increase efficacy and reduce the amount of each toxic substance. Hamlet Pharma expects that this approach will broaden the use and reduce the time to market for Alpha1H.
Recently, a preliminary statement from the Czech authority, SUKL, indicated that it will be possible to include combination therapy as one more variable in the ongoing bladder cancer study, in addition to the analysis of Alpha1H alone. A substantial amendment will therefore be submitted shortly for formal approval. This approach would offer a strategic advantage for progression to phase III clinical trials, and ultimately for approval by international pharmaceutical regulatory bodies such as the FDA.
 K.D. Sievert et al, Department of Urology, Univerity of Tübingen, World Journal of Urology (2009), 27:295-300
For more information, please contact
Catharina Svanborg, Chairman and founder of Hamlet Pharma, +46-709 42 65 49
Mats Persson, CEO Hamlet Pharma, +46 705 17 67 57
About HAMLET Pharma www.hamletpharma.com
HAMLET Pharma, listed on Spotlight, develops drugs based on the unique tumoricidal protein-lipid complex, HAMLET, formed by two natural and harmless molecules found in breast milk. Development focuses primarily on drugs, for the treatment and prevention of cancer. HAMLET kills tumour cells and has proven safe in proof-of-concept studies in animal models. Alpha1H is the synthetic variant of HAMLET, which has enabled development of the agent for clinical trials. Alpha1H kills different types of tumour cells and has demonstrated therapeutic effects on bladder cancer in animal models. Hamlet Pharma has one ongoing Phase I/II clinical trial with Alpha1H in patients with bladder cancer, a costly form of cancer that is difficult to treat, and intends to expand its activities into other types of cancer. The first results from the ongoing clinical Phase I/II study shows no side effects of Alpha1H, indicating that the treatment is safe and well tolerated. Alpha1H also demonstrated clinical efficacy compared with patients who received placebo.