Long-awaited Phase III data of ImClone Systems Inc.'s Erbitux in first-line metastatic colorectal cancer proved positive Wednesday, indicating the therapy met its primary endpoint.

That's news the New York-based company needed, considering a looming threat with competitor Amgen Inc.'s Vectibix (panitumumab), which was approved last September for third-line therapy, not to mention last year's management shake-up involving minority shareholder Carl Icahn.

"Given all that transpired," said Brian Rye, an analyst with Janney Montgomery Scott LLC in Philadelphia, "I think it's fair to say that this is a company that could use a bit of positive news."

While ImClone's shares (NASDAQ:IMCL) climbed a modest 5.3 percent, $1.56, to end the day at $29.22, Amgen's shares (NASDAQ:AMGN) barely wavered, falling only 23 cents Wednesday, to close at $71.27. Amgen's drug is behind Erbitux in development, but its efficacy data appear to be superior, although there has been no head-to-head trial of the two drugs.

ImClone did not give specifics on the Phase III data, except to say that the use of Erbitux (cetuximab) plus FOLFIRI (an irinotecan-based chemotherapy) met the primary endpoint of increasing median duration of progression-free survival over FOLFIRI alone in untreated metastatic colorectal cancer patients. The trial included more than 1,000 patients and was conducted by Merck KGaA, of Darmstadt, Germany, ImClone's ex-North American partner. Detailed data are expected to be presented in June at the American Society of Clinical Oncology (ASCO) meeting in Chicago.

Without knowing the magnitude of the response seen, Rye said it's difficult to get a sense of Erbitux's potential in first-line therapy. He expects the company to file with the FDA in the coming months, but in the meantime, the topline data will "provide some energy behind the Erbitux marketing effort," and possibly, "stem the tide, if there is any" of doctors leaving Erbitux for Vectibix.

Erbitux received approval in February 2004 for its use with irinotecan in epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer patients who are refractory to irinotecan-based chemotherapy, and as a single agent for those intolerant to irinotecan-based therapy. The drug's effectiveness is based on objective response rates, but available data have not demonstrated an improvement in disease-related symptoms or increased survival.

Amgen's drug, on the other hand, is the first EGFR inhibitor to show a statistically significant improvement in progression-free survival in those who have failed standard chemotherapy. The Thousand Oaks, Calif.-based company is working to expand the Vectibix label for use as a second-line therapy and, eventually, a first-line therapy.

South San Francisco-based Genentech Inc.'s drug Avastin currently treats first-line metastatic colorectal cancer patients in combination with FOLFIRI. It received approval in February 2004 following impressive data reported at the ASCO meeting in 2003.

"If the results from Erbitux are just overwhelmingly positive and look better than what Avastin showed, I think there's a chance you could see meaningful penetration in the front-line setting," Rye said. He later added that an expanded label to first-line "could help boost peak annual sales down the road by a couple hundred million dollars."

Erbitux earned net sales of $174.6 million in the third quarter. ImClone's North American partner Bristol-Myers Squibb Co., of New York, posts the sales and gives ImClone a 39 percent royalty. Vectibix was launched toward the end of last year, and Rye is expecting Erbitux sales to be down as a result.

"We won't know for sure until both companies report their fourth quarter results," he said. "We haven't seen any official numbers yet, but, yes, we are expecting Vectibix will have some impact."

Erbitux gained FDA approval for head and neck cancer last March, and it is being developed in Phase III trials for other cancer indications. Upcoming data expected by investors in the next few months will be from a study combining Erbitux with gemcitabine for pancreatic cancer patients.

If positive, "that could help provide another tumor type to help differentiate" Erbitux from Vectibix, Rye said.

ImClone's topline data in first-line metastatic colorectal cancer steals attention away from last year's squabbles between billionaire Carl Icahn and the company's management. Icahn had sought stockholder approval to remove six of the 12 board members, including Chairman David Kies and CEO Joseph Fischer. A minority stockholder, Icahn controls four of the board's seats.

The board recommended that shareholders refuse consent to Icahn's proposals and said in an SEC filing that Icahn asked for a waiver allowing him to purchase more than 15 percent of the company's common stock without making a tender offer to all stockholders. The directors he was trying to remove refused to grant the waiver, the filing stated. It also noted that Icahn refused a proposed acquisition earlier in the year of $36 per share. He joined the board in August when ImClone nixed its plans to merge with another entity. (See BioWorld Today, Aug. 11, 2006.)

Since then, Chief Financial Officer Michael Howerton resigned, as did Chairman Kies and board member William Crouse. Interim CEO Fischer eventually stepped down, and directors Vincent DeVita, John Fazio and William Miller will not stand for re-election at the annual meeting this year. Icahn was named chairman in October.