By Jim Shrine

ImClone Systems Inc. got FDA approval to begin Phase III trials of its lead cancer product, C225, triggering a $5 million milestone payment from partner Merck KgaA.

The drug will be tested with radiation therapy against advanced squamous cell head and neck cancers in what is the first in an expected series of pivotal studies of the monoclonal antibody, which inhibits the epidermal growth factor receptor. The 416-patient trial pits that combination against radiation alone.

¿Our strategy is to look at head and neck cancer as the indication [in which] we plan to get approval for C225,¿ said Harlan Waksal, ImClone¿s chief operating officer. ¿We¿re doing three different studies that will give us the potential to register this drug for approval. The earliest that would be completed would be in the middle of the year 2000.¿

Patients at 25 sites in the U.S. and Europe will get radiation therapy alone or radiation plus weekly infusions of C225. The primary endpoint is disease control one year following treatment. Enrollment is expected to take 18 to 24 months.

Waksal said the success (100 percent tumor regression) of radiation treatment in this indication ranges from 30 percent to 45 percent. A Phase Ib/IIa trial combining C225 and radiotherapy resulted in complete regression in 13 of 15 patients and more than 50 percent regression in the other two.

ImClone, of New York, and Merck, of Darmstadt, Germany, agreed in December to collaborate on development and marketing of C225 in a deal worth up to $90 million. ImClone retained North American rights and all manufacturing control. (See BioWorld Today, Dec. 16, 1998, p. 1.)

Collaboration Could Bring $30M By Year¿s End

Waksal said ImClone has received $11 million to date from the nearly three-month-old collaboration and expects to get another $9 million in milestones in the near term, while the total could reach $30 million by the end of the year. Another $30 million is tied to later-stage milestones such as filing and approval, and the final $30 million from the deal is in the form of a credit line for a facility to manufacture C225.

Other near-term milestones would be triggered by approval to start the European part of the trial, enrollment of the first patients, and the beginning of a separate trial comparing C225 and cisplatin against cisplatin alone in metastatic squamous cell cancers.

Waksal said ImClone expects to seek a go-ahead this month for the Phase III chemotherapy trial and is finalizing plans for a Phase III trial that combines C225 and chemotherapy agents in refractory squamous cell cancer patients. The study in refractory patients is expected to be the first pivotal trial of C225 completed.

Behind those studies are Phase II trials of C225 in renal cell carcinoma and pancreatic cancer. Also planned are studies in squamous cell cancers of the lung and colorectal cancer.

ImClone and Merck have a separate major collaboration on the cancer vaccine BEC-2, an anti-idiotypic monoclonal antibody in Phase III cancer trials in the U.S. and Europe. About 110 patients have been enrolled in that study, Waksal said. Another 18 to 24 months of enrollment is expected, then two years of patient follow-up.

ImClone¿s stock (NASDAQ:IMCL) gained 25 cents Tuesday to close at $11. n

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