Enhancing the efficacy of doxorubicin with heat-activated liposome technology
ThermoDox uses our LTSL (lysolipid thermally sensitive liposome) technology to encapsulate doxorubicin, a proven and commonly used cancer drug. The heat-sensitive liposome rapidly changes structure when heated to 40ºC-45ºC, creating openings in the liposome that release doxorubicin directly into and around the targeted tumor.
Delivers 25 times more doxorubicin into tumors
ThermoDox leverages 2 facets of tumor biology:(1) tumors have leaky vasculature, which is permeable to liposomes and enables their accumulation within tumors, and (2) when heated, blood vessels in tumors become even more permeable, further increasing the accumulation of liposomes in tumors before releasing the doxorubicin. In animal models, ThermoDox has been shown to deliver 25 times more doxorubicin into tumors than does intravenous (IV) infusion alone, and 5 times more doxorubicin than standard liposomal formulations of the drug.
ThermoDox, delivered by IV infusion, is designed to be used in combination with heat-based treatments, such as radiofrequency thermal ablation (RFA), microwave hyperthermia, or high-intensity focused ultrasound (HIFU). The goal is to expand the effective treatment zone in order to capture micrometastases, which are most commonly responsible for posttreatment disease recurrence.
In vivo: After 1 hour at 42ºC, heat-sensitive formulation delivered greatest volume of drugs to tumor
In vitro: Drug release occurs at clinically achievable temperatures
Two-year overall survival benefit in the HEAT subgroup analysis
The chart below shows the most recent subgroup analysis of our previously completed HEAT study for patients with primary liver cancer. These data highlight the power of ThermoDox plus RFA when used for ≥45 minutes on patients with single lesions only (n=285). The data show a 2.1-year improvement in overall survival (OS) in patients with single lesions, 3-7 cm in size, treated with RFA≥45 minutes and ThermoDox vs ThermoDox plus RFA ≥45 minutes. This analysis was used to design the now enrolling phase 3 OPTIMA Study for patients with single lesions.
Survival data for single-lesion patients, with and
Studies using ThermoDox
The OPTIMA Study, launched in the second half of 2014, is a global, phase 3 clinical study designed to evaluate ThermoDox in combination with standardized RFA (sRFA ≥45) in primary liver cancer. The 2-arm, double-blinded, placebo-controlled, randomized study will enroll approximately 550 patients at up to 75 sites in North America, Europe, China, and the Asia-Pacific region. The primary endpoint is OS. The study is powered to demonstrate a 33% improvement in OS.
The EU-DIGNITY Study is designed to assess the efficacy and tolerability of the combination of heat-activated target therapy (RFA+ hyperthermia + ThermoDox) in patients with recurrent chest wall breast cancer (RCW). The study is taking place in Europe and Israel and will enroll 70 patients.
Disease applications for ThermoDox
Primary liver cancer, otherwise known as hepatocellular carcinoma (HCC) is one of the most common and deadliest forms of cancer worldwide. It ranks as the fifth most common solid tumor cancer. It is estimated that up to 90% of liver cancer patients will die within 5 years of diagnosis. The annual incidence is approximately 30,000 cases in the United States and approximately 40,000 cases in Europe. Worldwide, the incidence is rapidly growing at approximately 800,000 cases per year.
Recurrent chest wall (RCW) breast cancer. Breast cancer is the most common malignancy in women worldwide. Despite a variety of therapeutic approaches, up to 40% of the estimated 95,000 patients in the United States undergoing a mastectomy as their primary treatment will develop locally recurrent RCW breast cancer. There is currently no effective chemotherapeutic standard of care for RCW breast cancer and, as a result, many of these patients will die within 2 years of the recurrence.
ThermoDox early access program
For patients with HCC, an early access program (EAP) is available in the European Union, Switzerland, Turkey, and Israel. For patients with RCW, one is available in the European Union, Switzerland, and Turkey, in centers where superficial hyperthermia devices are used.
EAPs allow biopharmaceutical companies to provide eligible patients with ethical access to investigational medicines for unmet medical needs within the scope of the existing early access legislation. Access is provided in response to physician requests, in a fully compliant manner, where no alternative medicinal treatment options are available to these patients.
For more information about the HCC early access program, please visit HCC EAP
For more information about the RCW breast cancer early access program, please visit RCW EAP
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