Threshold Pharmaceuticals Inc. (NASDAQ:THLD
) said the European
Commission has granted Orphan Drug Designation for TH-302, a
hypoxia-targeted drug, for the treatment of soft tissue sarcoma.
TH-302 is a hypoxia-targeted drug that is thought to be activated
under tumor hypoxic conditions, a hallmark of many cancer indications.
Areas of low oxygen levels (hypoxia) within tissues are common in many
solid tumors due to insufficient blood vessel growth. Similarly, the
bone marrow of patients with hematological malignancies has also been
shown, in some cases, to be extremely hypoxic.
Sarcomas are a group of aggressive cancers of connective tissue of
the body for which there are currently limited treatment options. Soft
tissue sarcomas are treated with surgery, chemotherapy and radiation.
company is currently conducting a pivotal Phase 3 study in soft tissue
sarcoma comparing TH-302 in combination with doxorubicin against single
The same combination regimen of TH-302 with doxorubicin was
investigated in the single-arm Phase 2 (TH-CR-403) study. Data from this
Phase 2 study were most recently presented at the Connective Tissue
Oncology Society (CTOS) meeting in October of 2011.
Doxorubicin as a single agent or in combination with ifosfamide are
the most commonly used chemotherapeutic regimens in patients with
advanced soft tissue sarcoma, but response rates are generally low and
toxicity can be significant.
In February 2011, Threshold said it had reached agreement with the
U.S. Food and Drug Administration on a Special Protocol Assessment for
the Phase 3 study (TH-CR-406) which includes a primary efficacy endpoint
of overall survival.
The international, randomized, controlled Phase 3 clinical trial was
initiated in September 2011, and is being conducted in partnership with
the Sarcoma Alliance for Research through Collaboration (SARC). The
trial is designed to enroll 450 patients with metastatic or locally
advanced unresectable soft tissue sarcoma.
Chief Executive Barry Selick said the Orphan Drug Designation was
granted as early studies of TH-302 have shown that it might be of
significant benefit for patients with soft tissue sarcoma when combined
The American Cancer Society estimates that 10,980 people were
diagnosed with a soft tissue sarcoma in the United States in 2011, and
about 3,920 people died from the disease. In Europe, it is estimated
that more than 32,000 people were diagnosed with soft tissue sarcoma in
TH-302 has been investigated in over 600 patients in Phase 1/2
clinical trials to date in a broad spectrum of tumor types, both as a
monotherapy and in combination with chemotherapy treatments and other
targeted cancer drugs.
Threshold has several additional ongoing clinical trials, the most
advanced of which is a Phase 3 pivotal study evaluating TH-302 in
combination with doxorubicin versus doxorubicin alone in patients with
soft tissue sarcoma, and recently completed a Phase 2b trial of TH-302
in combination with gemcitabine versus gemcitabine alone in pancreatic
THLD closed Thursday's regular trading down 3.72% at $6.73. The stock
has been trading between $1.18 and $7.50 for the past 52 weeks.