Project SA-033 for treatment of liver cancer and other BeloGal®-platform projects
The BeloGal®-platform, which was invented by the company, facilitates targeted delivery of drugs to selected organs and tissues. SA-033, the first drug candidate of the company based on BeloGal®-technology, enables delivery of the well-known cancer drug doxorubicin to the liver, significantly decreasing the adverse effects and increasing the chance to improve the treatment of liver cancer patients. Based on recent preclinical results, DBP plans to start clinical trials with this product and the company is now looking for a partner for the clinical development of SA-033. The BeloGal®-technology mimetically discriminates between, e.g., the lung or the liver from the rest of the body. By that reason, DBP has also applied the BeloGal®-technology in developing further projects such as SA-083 and SA-042, which are based on lung delivery. Up to now the BeloGal®-platform has been successfully applied on doxorubicin and doxycycline (antibiotic) but can be extended to be applied on the majority of drugs.
The preclinical results in rats and rabbits above show that lung-BeloGal® (SA-083) increases lung exposure to doxorubicin 10 times. The liver-BeloGal® (SA-033) increases liver exposure to doxorubicin 4 times while simultaneously the toxic heart exposure of doxorubicin is reduced about 2 times for SA-033 versus “standard” doxorubicin based on a dose-compensated comparison. Further toxicological studies supporting the future clinical studies have also been conducted, generally demonstrating less toxicity for SA-033 compared to a ‘standard’ doxorubicin formulation at equivalent doses of doxorubicin.
Preparation for the production of the GMP batch to be used in the first clinical study of SA-033
In order to start the first clinical trial, preparations for the GMP batch is proceeding. Subsequently, a Contract Manufacturing Organization (CMO) has been selected and the first feasibility batches have been produced and analysed. Technical and GMP batches are planned.
DBP is planning to start the first clinical study (Phase I trial) of SA-033 in 2018 in patients suffering from hepatocellular carcinoma.
The performed preclinical program and the future clinical studies were discussed at a scientific advice meeting with the Swedish Medical Products Agency in December 2014 with encouraging and fruitful results.
Double Bond Pharmaceutical AB was granted Orphan Drug Designation Status for SA-033 by the European Medicines Agency in June 2015 for the treatment of hepatoblastoma (HB), which is a primary malignant liver tumour and the most common type of liver cancer that affects children. The Orphan Drug Designation Status for SA033 obtained by DBP, gives ten years of market exclusivity for the indication and various kinds of support from EMA to further facilitate and accelerate the development of the product.
Competitors/Differentiation versus competitors
Sorafenib is the only approved drug on the market for the treatment of liver cancer but is only indicated for treatment of end-stage patients. Until now, loco-regional therapies such as resection, ablation, and trans-arterial chemoembolization (TACE) have been used extensively to treat liver cancer but all of them have disadvantages. E.g., resection can only be used in relatively healthy patients while ablation and TACE techniques can only be used on single tumours. SA-033 is designed to treat patients in different stages of liver cancer and to simultaneously treat the main tumour and possible metastases.
Market and potential
Today there is only one drug, sorafenib, which is approved for treatment of hepatocellular carcinoma as mentioned above. This treatment is only recommended for just a few percentages of the patients with liver cancer, being those with an advanced stage of the cancer and often with serious and irreversible liver damages. A therapy based on SA-033 will not only be able to cover a larger proportion of the patients diagnosed with primary liver cancers but also secondary cancers in the liver. Thus, the market for SA-033 is estimated to be doubled compared to that for sorafenib. According to FiercePharma (http://www.fiercepharma.com) the sales of sorafenib was approximately 1 billion USD and the market is expected to grow by approximately 50% until 2018.