Project Temodex for treatment of brain cancers
Temodex is a novel locally acting form of temozolomide developed by the Research Institute of Physical and Chemical Preparations at Belorussian State University in Minsk, Belarus, and has successfully been tested in clinical trials.
The current standard of care treatment prolongs the survival in patients but there is a large need for improved remedies. Temodex, offering such an improvement, is a gel that is locally administered in the cavity formed after resection of brain tumours. Thereby it can start to act against remaining tumour cells immediately after the removal of the tumour.
Temodex targets selectively tumoral tissues; it has anti-neoplastic effect; it has minimum influence on adjacent brain tissues; it has no severe systemic toxicity; and it is eliminated rapidly.
The Belorussian State University did receive a 1-st grade Diploma and a gold medal at RESTEC® HiTech exhibition forum in St. Petersburg for the development of Temodex in the category “Best Innovation Project: successful product marketing, best manufacturing, best stock handling and best logistics“ in 2015. Temodex is registered as a first line treatment of glioblastoma in Belarus since 2014.
Glioblastoma, the most common and aggressive malignant form of all primary brain tumors, affects glial cells and accounts for 52% of all brain tissue tumour cases and 20% of all tumours inside the skull. About 50% of the patients diagnosed with glioblastoma die within one year, and 90% within three years. Temodex has shown a prolonged survival with 9 month in patients with glioblastoma and other malignant astrocytic, oligodendroglial and oligoastrocytic brain tumours. The median survival time from the time of diagnosis without any treatment is only 3 months, and it is very difficult to treat glioblastoma due to several complicating factors. Surgery is the primary treatment of the disease.
Temozolomide, the active pharmaceutical ingredient in Temodex, is an imidazotetrazine derivative of the alkylating agent dacarbazine - an oral chemotherapy drug which is considered to be a prodrug. Temozolomide is used for the treatment of several brain cancer forms, e.g., as a second-line treatment for astrocytoma and as a first-line treatment for glioblastoma. The therapeutic benefit of temozolomide is due to its ability to alkylate/methylate DNA. This alkylation/methylation destroys the DNA and triggers the death of the tumour cells.
Double Bond Pharmaceutical AB has acquired global rights for Temodex from the Research Institute of Physical and Chemical Problems (RI PCP) in Belarus in October 2015. DBPs market share covers all countries except the Eurasian Economic Union (Russia, Belarus, Kazakhstan, the Republic of Armenia, the Kyrgyz Republic), and Ukraine. Temodex was registered as a first line treatment of glioblastoma in Belarus 2014. Double Bond Pharmaceutical is currently focused on the registration of Temodex in EU, USA and other major markets.
Clinical studies performed
A phase II study has been performed at a single site in Belarus, comparing standard of care plus Temodex with solely standard of care. Forty one patients with malignant supratentorial brain tumours of Grade II-IV were included and compared with a historical control of 95 patients. Standard of care in Belarus is constituted of surgery followed by radiation therapy and concomitant temozolomide during 6 weeks followed by adjuvant temozolomide for up to 6 cycles. The median progression free survival was significantly longer for patients in the Temodex group compared to the control group: 16.1 versus 8.2 months, respectively. The median overall survival was also significantly longer for patients in the Temodex group compared to the control group: 18.3 versus 9.8 months, respectively. Adverse events during the first ten days after surgery were observed in nearly 10% of patients in the Temodex group versus in 13% of patients in the control group. Overall, the type and frequency of adverse events in the Temodex group did not differ from those in the control group.
Orphan drug designation status in Europe
Double Bond Pharmaceutical AB was granted Orphan Drug Designation for Temodex by the European Medicines Agency in June 2016 for the treatment of glioma. The Orphan Drug Designation Status for Temodex 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.
Further development of Temodex in Europe
Further preclinical and clinical development of Temodex (SI-053) for the registration and marketing authorization in EU, USA and worldwide is on-going. European clinical trials are planned to be started during 2018.