Two weeks after reaching agreement with the FDA on a special protocol assessment, Ariad Pharmaceuticals Inc., along with partner Merck & Co. Inc., launched a Phase III trial to test the effect of deforolimus on progression-free survival in patients with metastatic soft-tissue and bone sarcomas.

The start of the SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Deforolimus) study is "a very important step for us," said Harvey Berger, chairman and CEO of Cambridge, Mass.-based Ariad, "and provides the foundation for a new treatment for patients with bone and soft-tissue sarcoma." In fact, he added, pending successful results, deforolimus, a small-molecule compound that targets mTOR (mammalian target of rapamycin), could become the first new treatment in that indication in more than 20 years.

In early studies, deforolimus demonstrated an ability to block the mTOR, a protein that acts as a master switch in cancer cells, thereby turning off the ability for cancer cells to grow, divide, metastasize and form new blood cells. The Phase III SUCCEED trial is designed as a double-blind, placebo-controlled study of oral deforolimus in metastatic sarcoma patients who have achieved a favorable response to chemotherapy, the point that represents a treatment vacuum for those suffering from the aggressive connective-tissue cancers. Current standard of care calls for patients who have responded to chemotherapy to either continue a toxic chemotherapeutic regimen that has not established further clinical benefit, or to stop treatment and be closely monitored for disease progression, at which time they will begin a new round of chemotherapy.

Ariad's drug aims to fill that vacuum by preventing disease progression following chemotherapy treatment. The SUCCEED study is expected to enroll about 650 patients to be randomized on a one-to-one basis to receive either Ariad's drug or placebo. "We agreed with the FDA that median progression-free survival was the most relevant endpoint," Berger told BioWorld Today, and the trial is 90 percent powered to detect a 33 percent increase in median PFS. Overall survival will be the secondary endpoint.

Targeting mTOR already has proved successful in extending progression-free and overall survival on other indications. Madison, N.J.-base Wyeth gained FDA approval in late May for Torisel (temsirolimus) in advanced renal-cell cancer based on data showing that it increased survival compared to interferon-alpha. Wyeth also is investigating Torisel in mantle-cell carcinoma.

Ariad estimates about two years between starting the SUCCEED study and the completion of both patient enrollment and the second of two planned interim analyses, though Berger said that "we expect it will probably take less [time] than that." Results of the trial, if successful, should be "robust and clear-cut" and sufficiently form the basis for a regulatory filing, he added.

Deforolimus has both fast-track and orphan drug designation from the FDA for soft-tissue and bone sarcomas, a disease that affects about 100,000 in the U.S. It also gained orphan drug status in the European Union.

Ariad and Merck are jointly funding the SUCCEED study, according to the terms of the companies' July agreement. Whitehouse Station, N.J.-based Merck paid Ariad $75 million up front, with the potential for up to $452 million in potential milestones, pending the successful development of deforolimus in several oncology indications. Among those milestones is an upcoming payment of $13.5 million that will be due upon dosing of the first patient in the pivotal sarcoma trial. The drug is being studied in hormone-refractory prostate cancer, endometrial cancer, leukemia and lymphoma and brain cancer, though the companies have not yet disclosed which indication they will pursue after sarcoma. Under the worldwide agreement, Ariad and Merck intend to co-promote the drug in the U.S., while Merck will sell deforolimus outside the U.S., with royalties to Ariad. (See BioWorld Today, July 13, 2007.)

Shares of Ariad (NASDAQ:ARIA) gained 11 cents Monday to close at $4.99.