Ziopharm license new arsenic drugs
into a licensing agreement for a new class of organic arsenicals
with the intention of developing them for a wide range of cancers
The licensing collaboration, which joins Ziopharm with The University of Texas opens the potential of expanding the modern-day version of arsenic, currently used to treat APL (acute promyelocytic leukemia), to the much more common hematologic and solid cancers.
The organic versions of arsenic are a new class of drug because as an anti-cancer therapy, they have not been previously developed. ZIO-101 is an organified arsenic compound whose principle mechanism of action is induction of cell cycle arrest and anti-apoptotic pathways, and in malignant cells. It affects both caspase dependent and independent apoptotic pathways.
Although arsenic can be poisonous, and chronic arsenic exposure from industrial or natural sources can cause serious toxicity, Dose-limiting toxicities of inorganic arsenics, include damage to the liver, bone marrow and skin. Arsenic has been used in China where a high proportion of hematologic responses in patients with acute promyelocytic leukemia (APL) were treated with arsenic trioxide. Randomized clinical trials in the U.S. led to FDA approval of arsenic trioxide for relapsed or refractory APL in September 2000.
ZIO-101 has been shown to be substantially safer than inorganic arsenics like arsenic trioxide. Animal studies show the ability to give 5- to 10-fold more ZIO-101 than arsenic trioxide without damaging the heart.
A large dose increase, possible with ZIO-101, is expected to allow cancer physicians to take advantage of arsenic's ability to kill cancer cells specifically by causing cell cycle arrest and cell death rather than cell differentiation, as is the case with inorganic arsenic.
Mark Thornton, Chief Medical Officer at Ziopharm told DrugResearcher.com: "The FDA has mandated warnings to patients and doctors that arsenic trioxide can cause QT prolongation and complete AV block which can be fatal.
"We feel that with ZIO-101, the patient will be able to be exposed to significantly greater amounts of arsenic before onset of toxicity."
"Carcinogenicity has been associated with chronic, low-dose exposure to inorganic arsenic. We are not aware of any relationship between carcinogenicity and acute organic arsenic exposure as would occur with ZIO-101," Thornton added.
Thornton said that Ziopharm are still in the process of finalizing protocol details. Phase I studies in adults with blood cancers and lymphomas are expected to begin in 1Q of 2005. Parallel Phase I studies in solid cancers are planned for late 2Q-2005. Once the maximum tolerated dose is determined, Phase-II studies are planned in both hematologic and solid cancers.
