November 11, 2014
By Jessica Wilson, BioSpace.com Breaking News Staff
Threshold Pharmaceuticals today announced that the U.S. Food and Drug Administration (FDA) has awarded the company’s investigational anticancer drug TH-302 Fast Track designation for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma (STS).
South San Francisco-based Threshold said the Fast Track designation is significant because the FDA may evaluate completed parts of the drug’s New Drug Application (NDA) before the company submits the entire application. The FDA established the Fast Track designation to expedite the approval of drugs that treat life-threatening diseases and that could address unmet medical needs.
“We are pleased that FDA has granted Fast Track status for TH-302 for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma,” Barry Selick, chief executive officer of Threshold, said in a statement. “Our ongoing Phase 3 trial of TH-302 in these patients is being conducted under a Special Protocol Assessment with the FDA. If successful, the Fast Track designation may provide an added benefit of facilitating the NDA review process. Currently, we anticipate the primary analysis of overall survival of the Phase 3 trial to be conducted in the first quarter of 2016.”
The randomized Phase 3 trial involves 640 patients across 81 study sites in Europe, Israel, North America and the Russian Federation. One group is receiving TH-302 in combination with doxorubicin, a chemotherapy agent, and the other group is receiving only doxorubicin. The overall survival of the patients is the primary endpoint. Secondary endpoints include progression-free survival, overall response rate, pharmacokinetics and safety.
Soft tissue sarcoma, an aggressive cancer, attacks the connective tissues of the body. The current treatments available for the disease include surgery, chemotherapy and radiation. Doctors use most commonly doxorubicin and ifosfamide as the chemotherapeutic agents for patients’ treatments. Patients’, however, often do not respond to the treatments and experience high toxicity with them. According to the American Cancer Society, in 2014, “About 12,020 new soft tissue sarcomas will be diagnosed (6,550 cases in males and 5,470 cases in females). In addition, 4,740 Americans (2,550 males and 2,190 females) are expected to die of soft tissue sarcomas.”
Threshold’s TH-302, called a hypoxia-activated prodrug, works by targeting regions of tumor hypoxia within tumor cells. A characteristic of many cancers, hypoxia regions are areas of low oxygen levels formed by insufficient blood supply, usually because of shrunken blood vessels. Researchers believe that tumor hypoxia contributes to treatment failure because the chemotherapeutic agents cannot research the cancerous areas via the smaller blood vessels. In addition, chemotherapeutic drugs target rapidly dividing cells and it’s possible that cancer cells in hypoxic regions divide significantly more slowly because they receive fewer nutrients and less oxygen than cancer cells in non-hypoxic regions. Both of these conditions could cause, at least partly, the failure of current treatments of STS.
