Washington Editor

Under new management, ImClone Systems Inc. cleared a regulatory hurdle that tripped up the company's previous executives.

Nearly two years after refusing to accept for filing ImClone's biologics license application for the investigational cancer drug Erbitux, the FDA accepted for review the New York-based company's new BLA, complete with data from a promising Phase II trial handled by overseas partner Merck KGaA, of Darmstadt, Germany. And, to add icing to the cake, Erbitux has been granted accelerated approval and priority review designation.

That means if all goes well, the FDA likely will take action by Feb. 13.

ImClone, and partner Bristol-Myers Squibb Co., also of New York, are requesting approval of Erbitux (cetuximab) in combination with irinotecan for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing irinotecan-refractory metastatic colorectal cancer.

Daniel Lynch, acting CEO of ImClone, in a prepared statement referred to the acceptance as a significant milestone.

"We are pleased that the FDA has granted the filing a six-month priority review period," he said. "We look forward to working closely with the FDA through the remaining months of the review period toward the goal of getting Erbitux as quickly as possible to the many patients with metastatic colorectal cancer whose tumors no longer respond to irinotecan-based therapy."

A BMS spokesman told BioWorld Today the company would not comment beyond ImClone's prepared statement.

ImClone's stock (NASDAQ:IMCL) dipped $3.50 Monday to close at $38.50.

For ImClone, climbing out of the single-digit price range for its stock has been painful. In early 2002, ImClone dropped as low as $5 a share, in part because of the insider trading scandal that erupted when former CEO Samuel Waksal, his family and his friend Martha Stewart sought to dump company shares days ahead of the FDA's refusal to file for the original Erbitux BLA. Waksal also caused controversy by telling analysts that the FDA denial stemmed from a mere "train of documentation" that was missing. (See BioWorld Today, Jan. 3, 2002; Jan. 27, 2002; and Feb. 28, 2002.)

Today, Waksal is serving a seven-year prison sentence on fraud and insider trading charges, while Stewart is preparing to answer to charges in January. As for Waksal's family, his brother Harlan, who has served as ImClone's CEO, chief scientific officer and director, also resigned. Their 82-year-old father, Jack Waksal, a Holocaust survivor, has been charged with selling more than $8 million in stock based on a tip from Samuel Waksal. (See BioWorld Today, May 1, 2003, and July 22, 2003.)

With the scandal behind them, ImClone, BMS and Merck are waiting for regulatory approval.

ImClone and BMS in August filed the new BLA including data from the Merck trial released in June at the annual meeting of the American Society of Clinical Oncology in Chicago. (See BioWorld Today June 3, 2002, and Aug. 15, 2003.)

Referred to as Trial 007, the study looked at 329 patients with irinotecan-refractory colorectal cancer that expressed EGFR (usually a marker of fast advance). Merck said Erbitux in combination with irinotecan slowed progression of the disease by more than four months, shrinking tumors by 50 percent or more in 22.9 percent of patients. Merck filed for European approval in July. (See BioWorld Today, July 8, 2003.)

ImClone currently is conducting two Phase III trials (confirmatory studies) in second-line metastatic colorectal cancer.

David Pitts, a spokesman for ImClone, told BioWorld Today the Phase III trials are expected to be fully enrolled in 2004, and data should be ready in 2006.

The companies also expect to finish a single-arm Phase II in colorectal cancer later this year.

Erbitux is the subject of a Phase III study in head and neck cancer, and is being evaluated in other types of cancer that express the EGF receptor, including lung, pancreatic and ovarian cancers.

Erbitux is an IgG1 monoclonal antibody designed to exclusively target and block the EGFR, which is expressed on the surface of certain cancer cells in multiple tumor types. Erbitux is designed to bind to EGFR and prevent growth factors from binding to the receptor and inducing phosphorylation, activation of signaling to the tumor.