FDA lifts clinical hold on Genta's Tesetaxel

Genta Incorporated announced that the Company has received notification from the U.S. Food and Drug Administration (FDA) that Genta may resume clinical trials with tesetaxel, a leading oral taxane in Genta's oncology product portfolio.

The notification was made in response to the Company's submission of a complete response to a prior notice from FDA that had placed the drug on "clinical hold".

"We believe tesetaxel may provide an important option for the care of patients with advanced cancer," commented Dr. Loretta M. Itri, Genta's President, Pharmaceutical Development, and Chief Medical Officer. "We are very pleased that FDA found that our initial submission addressed their safety concerns by incorporating careful monitoring and supportive care to reduce risks. We have formulated an innovative development strategy that may enable tesetaxel to become the first oral taxane to receive regulatory approval. We look forward to promptly resuming clinical trials in the second half of this year."

Tesetaxel is a novel, orally absorbed, semi-synthetic taxane that is in the same class of drugs as paclitaxel and docetaxel. However, both prototype agents suffer from serious safety issues, particularly hypersensitivity reactions related to intravenous infusions that are occasionally fatal and that require careful premedication and observation. Other prominent side-effects of this drug class include myelosuppression (low blood counts) and peripheral neuropathy (disabling nerve damage).

With administration as an oral capsule, tesetaxel was developed to maintain the high antitumor activity of the taxane drug class while eliminating infusion reactions, reducing neuropathy, and increasing patient convenience. The oral route also enables development of novel schedules that may expand dosing options when tesetaxel is used alone or in combination with other anticancer drugs. Preclinically, tesetaxel has demonstrated substantially higher activity against cell lines that were resistant to paclitaxel and docetaxel, since acquired resistance is not mediated by the multidrug-resistant p-glycoprotein.

As a late Phase 2 oncology product, tesetaxel has demonstrated anticancer activity in its initial clinical trials, and the drug has not been associated with the severe infusion reactions that are linked with other taxanes. Moreover, unlike other oral taxanes that are currently in clinical development, nerve damage has not been a prominent side effect of tesetaxel. Thus, the drug offers substantial opportunities to improve patient convenience, safety, and anticancer activity.

More than 250 patients worldwide have been treated with oral tesetaxel in Phase I and Phase 2 clinical trials. The major side-effect of tesetaxel in clinical trials has been myelosuppression, chiefly neutropenia. Due to the occurrence of severe neutropenia that led to fatal outcomes in several patients with advanced cancer, the drug was placed on clinical hold by FDA. Resumption of clinical trials was subject to the lifting of this clinical hold.