Staff Writer

Onconova Therapeutics Inc. has reached agreement with the FDA on a special protocol assessment (SPA) for a Phase III trial of Estybon, a potential treatment for myelodysplastic syndromes – a set of blood disorders.

Patient enrollment in the pivotal trial is expected to begin in the fourth quarter. The trial, which will compare Estybon to standard-of-care treatments, is expected to enroll rapidly with patients seeking a new option.

As for the study's main objective, "Right now, the FDA is asking for survival as the endpoint rather than surrogate results," CEO Ramesh Kumar told BioWorld Today.

The bulk of the funding for the randomized trial will come from Onconova's own internal funds and also $10 million in support from the Leukemia & Lymphoma Society (LLS).

The Newton, Pa.-based company has not yet made a decision on whether it will take the drug to market on its own or with a partner, if approved. "We are open to both possibilities," Kumar said.

The Phase II data clearly were strong enough to justify a Phase III pivotal trial under an SPA. But specific data from the Phase II trial won't be presented until December at the annual meeting of the American Society of Hematology in Orlando.

The molecule has a multitargeted mode of action, blocking the PI-3 kinase, ERK (growth) and AKT (pro-survival) pathways. The work of Elaine Sloand, of the National Institutes of Health, and others has shown that a barrier exists in the MDS cells, preventing them from being killed. And that barrier sometimes manifests in high-risk MDS patients. But blocking the PI3K pathway relieves that barrier and allows the MDS cells to be killed, Kumar explained.

MDS is neither precancerous nor cancerous, but "right at the razor's edge," he said.

When the blast count (percentage of cancer cells) of MDS patients reaches a certain percentage (20 percent or higher), the disease is considered to be leukemic.

MDS is a group of diseases of the blood and bone marrow that occurs in 5 per 100,000 people. However, among those older than age 70, the incidence increases to between 22 and 45 per 100,000. The FDA has granted the drug candidate orphan status in MDS.

Typical treatments for MDS include blood transfusions, growth factors and antibiotics, but patients with drug-resistant disease have limited options. The only potential cure is stem cell transplantation, but MDS patients may not be candidates due to their advanced age and underlying bone marrow deficit, according to Onconova and LLS, which entered a collaboration for Estybon in June. It was the first approval-track clinical trial to be supported by the LLS therapy acceleration program.

Estybon (ON 01910.Na) also is being developed for other hematologic and solid tumor indications, both as single agent and in combination therapy. Onconova is developing Ex-RAD as a radiation protection drug (oral and injection) in collaboration with the Defense Department to be given pre-exposure or post-exposure to lethal radiation of tissue and whole body radiation injury.