Washington Editor

While ImClone Inc.'s former CEO Samuel Waksal waits to be sentenced on a series of fraud and other charges this week, the company he co-founded is pulling together a regulatory application on the long-awaited colorectal cancer drug Erbitux.

ImClone and partner Bristol-Myers Squibb Co., both of New York, said they would file a biologics license application for Erbitux (cetuximab) in the second half of this year, the second BLA on the drug that was rejected a year and a half ago by the FDA.

Both companies were tight-lipped about what the application would contain, saying they were not ready to release specifics. However, the news of another BLA sent ImClone's stock soaring - at least for a while. The company's stock (NASDAQ:IMCLE) was up 22 percent Friday morning (the news was released Thursday after the market closed), but by Friday afternoon, the gains melted away. The stock closed at $38.39, down 14 cents, although it is up significantly over the past few months.

Quite a change from the days when ImClone was worth $5 a share, thanks to the scandal caused by Waksal, his family and friend Martha Stewart, who allegedly dumped ImClone shares ahead of the FDA's rejection of the first Erbitux BLA filed in late 2001. (See BioWorld Today, Jan. 3, 2002; Jan. 27, 2002; and Feb. 28, 2002.)

The stock was trading as low as $9 in February but started turning in anticipation of pivotal Phase II results from another partner, Merck KGaA, of Darmstadt, Germany. On June 1, Merck presented data at the American Society of Clinical Oncology meeting in Chicago from the study, called Trial 007, in 329 patients with irinotecan-refractory colorectal cancer that expressed the epidermal growth factor receptor, or 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. (See BioWorld Today, June 3, 2003.)

Two-thirds of the trial patients were given Erbitux and irinotecan, while the remainder took Erbitux alone. Overall, the response rate was 11 percent for Erbitux alone. But when patients were given Erbitux with irinotecan, the number jumped to 23 percent, proving that the combination works even when patients have stopped responding to irinotecan.

Nevertheless, ImClone and BMS haven't officially stated that their BLA will include Merck data. Instead, Kathy Baum, a spokeswoman for BMS, told BioWorld Today simply, "We did talk to the FDA about Merck 007, but we haven't announced what will be in the package."

ImClone also has a Phase II single-arm study and recently initiated enrollment of two Phase III randomized trials for second-line metastatic colorectal cancer. Neither Baum nor Andy Merrill, ImClone's spokesman, would estimate a completion date on the Phase III studies.

Erbitux is a monoclonal antibody designed to target and block the epidermal growth factor receptor. The receptor is expressed on the surface of certain cancer cells in multiple tumor types.

As with the first BLA, ImClone intends to request accelerated approval, meaning the application could be cleared on a surrogate endpoint with Phase III trials in progress. Accelerated approval applications generally are reviewed and acted upon in six months.

When Waksal resigned from ImClone last spring, weeks before he was picked up on federal charges, his brother and company co-founder, Harlan Waksal, assumed the role of CEO.

Harlan's tenure lasted about a year. He ended up stepping aside about a month ago in connection with an internal review related to the company's failure to withhold $60 million in taxes on executive stock options. Harlan now works as ImClone's chief scientific officer. (See BioWorld Today, May 1, 2003.)

The company was unable to file its 2002 Form 10-K because of its inability to finalize its audited financial statements. In compliance with an extension Nasdaq issued, ImClone released an update on its financial statement.

ImClone estimates that the liability to be stated on its Dec. 31, 2002, balance sheet will be about $41.2 million. The amount to be charged against earnings will be approximately $30.3 million, including about $25.6 million attributable to the withholding tax liability for Samuel Waksal. Both estimated amounts are exclusive of penalties, interest and other related contingencies.

As per an agreement with Nasdaq, ImClone must file its 10-K on or before June 23, and its 10-Q on or before July 7. Merrill said the company believes it can meet those deadlines.

ImClone says it has enough cash to take it through June 2004. The next scheduled BMS milestone would be issued when Erbitux is cleared for regulatory approval.