Hamlet: HAMLET Pharma's strategic decision - Our first clinical trial in patients with urinary bladder cancer
In this Issue:
- Why Bladder cancer?
- Treatment methods
- Hamlet treatment of Bladder cancer
- Market and perspective
Why Bladder cancer?
Bladder cancers are common, costly and few new treatments have been developed in recent years. The aim of HAMLET Pharma is to develop efficient therapy for bladder cancer, with few side effects. Our drug candidate is Alpha1H.
Bladder cancer is the sixth most common cancer in Sweden and the mortality rate is approximately 600 cases per year. Bladder cancer is the ninth most common cancer world-wide and represents 3.3% of the more than 10 million new cancer cases that occur each year with an estimated mortality of about 170 000.
In addition, the lifetime treatment costs per patient is very high, due to frequent recurrences and a need for invasive monitoring. Depending on the country, the lifetime cost per patient ranges from $96,000 to $202,000. In the US, total cancer costs were estimated at $206.3B with estimated $17.9B for bladder cancer-related morbidity and $110.2B for cancer-related mortality. A further increase occurred in 2012, when an estimated $4.1 billion was spent to treat bladder cancer in the US. The diagnosis and care of bladder cancer thus represents a significant financial burden for patients and society, worldwide.
Following a diagnosis of bladder cancer, surgery is used in > 90% of cases. Transitional cell carcinomas are usually confined to the bladder mucosa and surgery is often followed by local instillations of BCG bacteria or cytostatic drugs. These treatments may result in prolonged tumor-free periods but recurrences are common and there is a need for less toxic and more specific therapies. More advanced cancers may require removal of the entire bladder (cystectomy). Patient outcomes are improved with the use of chemotherapy, alone or with radiation before cystectomy but these treatments come with the cost of increased side effects. Metastatic cancers are typically treated with chemotherapy, sometimes along with radiation. Most patients, who die of bladder cancer, have metastatic disease, usually in regional lymph nodes, lung, liver and bone.
Hamlet treatment of Bladder cancer
We selected bladder cancer as a first clinical indication, due to the positive effects that we have observed in a previous clinical study and in experimental models.
1. Clinical study (International Journal of Cancer, 2007).We injected HAMLET into the bladder of patients, who were waitlisted for bladder surgery. HAMLET was administered daily for five days and the tumor was inspected before and after this period. Several interesting observations were made.
- Local bladder instillations of HAMLET caused massive tumor cell shedding into the urine. Most tumor cells that came out were dead.
- The appearance of the tumor changed after the HAMLET instillation. After treatment, the tumor showed a reduction in size and character.
2. Murine bladder cancer model (Journal of Urology). We also injected HAMLET into the bladder of mice with bladder cancer and measured the effect compared to a control group that did not receive HAMLET. HAMLET treatment resulted in a marked delay in tumor growth.
3. Importantly, the patients suffered no toxic side effects and healthy adjacent tissue showed no evidence of toxicity in patients or mice.
The results show that Hamlet causes tumor shrinkage and drives the secretion of dead tumor cells into urine in patients with bladder cancer, apparently without toxic effect. These observations distinguish HAMLET from other, more toxic treatment methods used in bladder cancer.
These findings have persuaded HAMLET Pharma to choose bladder cancer as the first indication to test the therapeutic value of HAMLET in controlled trials. We plan to conduct a study of topical HAMLET administration into the bladder. Local administration of drugs into the bladder is widely used, making the HAMLET study ethically and practically feasible.
Market and perspective
Bladder cancer and its complications contribute to patient suffering and costs for society. Identifying new treatments and more cost-effective surveillance strategies are essential. In addition, there is a need for new approaches to preventing bladder cancer, thereby minimizing the clinical and economic consequences.
Given the aging population and the continued technological advances likely to occur over the next decade, such as new urinary markers for bladder cancer, improved endoscopy, and the evolving role of minimally invasive surgery, managing patients with bladder cancer will likely become much more costly than it is today. Thus, there will be growing pressure to contain costs and more efficiently manage care and societal resources.
The aim of HAMLET Pharma is to develop sustainable treatments for patients with bladder cancer and other forms of cancer. After all, HAMLET has been found to kill > 40 types of cancer cells, and we are exploring HAMLET’s other potent capabilities against different cancer indications through licensing agreements and collaborations.
For More information please visit Hamletpharma.com
For more information, please contact
Catharina Svanborg, Chairman of the board, Hamlet Pharma, +46-709 42 65 49
Mats Persson, CEO Hamlet Pharma, +46 705 17 67 57
About Hamlet Pharma
Hamlet Pharma AB owns and develops a new technology to kill cancer cells without harming healthy tissues. The HAMLET technology is focused around the HAMLET family of tumoricidal protein-lipid complexes, formed by naturally occurring molecules from human milk and extended to include recombinant variants of the natural substance. HAMLET has validated therapeutic efficacy in clinical studies and animal models, and in many different cellular models of human cancer. Alpha1 is a peptide that includes key tumoricidal motifs within HAMLET. Together with oleic acid, the peptide forms the Alpha1H complex that target cancer tissues selectively similar to HAMLET. Alpha1H will now be developed further for Phase II clinical trials, to verify the positive proof of concept studies. Hamlet Pharma AB shares are listed at AktieTorget. HAMLET is an abbreviation for Human Alpha-lactalbumin Made LEthal to Tumor cells.