More than a year after reporting promising Phase III results, ImClone Systems Inc. filed a supplemental biologics license application for Erbitux to treat squamous-cell carcinoma of the head and neck (SCCHN).

If the company and its North American partner Bristol-Myers Squibb Co., both of New York, receive priority-review status from the FDA, an approval could come in early 2006, making head and neck cancer the second approved indication for Erbitux. The product was approved in early 2004 for colorectal cancer.

The sBLA filing for SCCHN originally was expected in the second quarter, but it was delayed so the company could conduct an additional independent analysis of the primary endpoint. (See BioWorld Today, April 14, 2005.)

"In our opinion, this is a significant, but expected event," said Cory Kasimov, an analyst with New York-based Oppenheimer & Co. "The results actually came out at ASCO in 2004, so we had clinical results over a year ago, and we've been waiting on this event for some time."

ImClone's stock (NASDAQ:IMCL) showed little movement on Tuesday, rising 12 cents to close at $32.72.

The company is seeking approval of Erbitux (cetuximab) in combination with radiation for locally or regionally advanced SCCHN, and as a monotherapy in those with recurrent and/or metastatic SCCHN in which prior platinum-based chemotherapy has failed or in which platinum-based therapy would not be appropriate.

The head and neck cancer market represents a $300 million to $500 million annual opportunity for Erbitux, Kasimov said, adding that the indication will only add to the drug's blockbuster potential.

"For some time, we have thought this drug has the potential to ultimately exceed $1 billion in annual sales. So that hasn't changed," Kasimov said. "That's why we say, in the end, this was an important event for the company, and it's one that was widely expected for some time and doesn't impact our investment thesis one way or another."

ImClone reported Erbitux sales of $97.8 million for the quarter ended June 30. The drug is in development for several other indications, such as lung cancer, pancreatic cancer and ovarian cancer.

The head and neck cancer indication is one that would have few competitors.

"Head and neck is more of an open playing field than colorectal cancer, where they're competing with products such as Avastin," Kasimov said.

South San Francisco-based Genentech Inc.'s Avastin, which was approved for colorectal cancer about the same time Erbitux gained clearance, had sales of $246 million in the second quarter. And Phase III data from another colorectal cancer drug, panitumumab, is expected to come later this year. That drug is being developed by Amgen Inc., of Thousand Oaks, Calif., and Abgenix Inc., of Fremont, Calif.

But it appears Erbitux would have a room to run in the head and neck cancer market.

"There haven't been any new drug introductions in head and neck, or new modalities of treatment in the head and neck population, in many, many years," said David Pitts, ImClone's assistant vice president of corporate communications. He explained that co-morbidities, such as liver and heart issues, often go along with head and neck cancer. "That makes drug companies wary to move into this population," he said.

But a pivotal trial of Erbitux has shown that the therapy can significantly increase patient survival. It demonstrated a median overall survival of 54 months, compared with 28 months for those not receiving the drug.

The sBLA filing is based on data from a randomized, international Phase III trial, conducted by ImClone and its rest-of-world partner Merck KGaA, of Darmstadt, Germany. The companies combined Erbitux with radiation on locoregional control in 424 patients. The submission also included data from an open-label, multicenter Phase II trial, conducted by Merck, which included 103 patients with recurrent and/or metastatic head and neck cancer who have failed platinum-based chemotherapy.

Concurrent with the ImClone and Bristol-Myers Squibb submission to the FDA, Merck filed for approval in Europe of Erbitux to treat head and neck cancer. The drug is approved in more than 40 countries for colorectal cancer.

ImClone first presented Phase III SCCHN data of Erbitux at the American Society of Clinical Oncology (ASCO) meeting in June 2004. Results showed that 69 percent of treated patients achieved locoregional control at one year, and 56 percent achieved it at two years, compared with 59 percent and 48 percent, respectively, of those treated with radiation alone. The percentage of patients alive at two and three years post-treatment was 62 percent and 57 percent for the Erbitux-treated patients vs. 55 percent and 44 percent for those treated with radiation alone. Both endpoints were statistically significant. (See BioWorld Today, June 8, 2004.)

ImClone's stock jumped more than 14 percent in June when independent reviewers confirmed that Erbitux worked in a Phase III study as a first-line therapy against squamous-cell tumors of the head and neck. That confirmation paved the way for the sBLA filing. (See BioWorld Today, June 9, 2005.)

About 40,000 Americans will be diagnosed with head and neck cancer this year, according to the American Cancer Society, and about 11,000 will die from the disease in 2005 in the U.S. Head and neck cancers include cancers of the tongue, mouth, pharynx and larynx.

Erbitux, an IgG1 monoclonal antibody, binds specifically to epidermal growth factor receptors on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor and other ligands.

The next clinical data to come for Erbitux will be in 2006, upon completion of late-stage pancreatic cancer studies. That could be followed later in the year by data on its use in first- and second-line colorectal cancer. It also is being studied in a Phase III lung cancer trial, begun last October. (See BioWorld Today, Oct. 11, 2004.)

In the meantime, ImClone will wait for the verdict on Erbitux in head and neck cancer.

"We're very pleased to have made this filing. It's obviously the first step in this review process," Pitts said. "And we'll work with the FDA to ensure the review will go smoothly."

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