Staff Writer

ImClone Systems Inc. and partner Bristol-Myers Squibb Co. announced late Tuesday that a supplemental biologics license application for Erbitux (cetuximab) as a treatment for head and neck cancer would not be filed this quarter, as previously announced.

"The delay is attributed to the time and logistics required to conduct additional independent analysis of the primary endpoint," ImClone Chief Medical Officer Eric Rowinsky said during a conference call Tuesday, adding that the company remained "confident in the ultimate feasibility of this application" and expected to file the supplemental BLA before the end of the year.

Wall Street wasn't pleased, as shares of ImClone (NASDAQ:IMCL) Wednesday fell more than 11 percent, or $4.13, to close at $31.18.

ImClone CEO Daniel Lynch said the delay is "unfortunate, but the decision to amend the review process is important to ensure a high-quality submission."

Due to the setback, ImClone might not earn its expected milestone payment for the Erbitux supplemental BLA this year. The company didn't comment on the financial impact of missing the payment, but expects to provide more information when its first-quarter earnings are released later this month.

ImClone and BMS reported in July that they had established a plan with the FDA for filing the supplemental BLA of Erbitux as a single agent and in combination with radiation in squamous-cell carcinoma of the head and neck. The companies expected to file this quarter and to request priority review. (See BioWorld Today, July 22, 2004.)

During the conference call, Rowinsky, who joined ImClone in February, explained that the company needed time to study IMC-9815 to evaluate its endpoint, which is defined as locoregonial disease control in the head and neck. The further review is intended to "balance" the process to make sure that data from each of the 424 patients involved in the study are analyzed as consistently as possible, he said.

Because of the difficulty in analyzing the data for locoregional control in head and neck cancer - not easily measured through radiographic scanning or X-rays - an independent clinical review committee was assembled to assess various tests used by investigators.

"Each patient will be reviewed by a medical oncologist and one radiation therapist" to determine whether they conform with locoregional control, Rowinsky said. If data from those two analyses yield differing opinions, an adjudicator would be brought in to review the results and make a final decision.

"We previously had no procedure for resolving that discordance," he said.

The process for completing the independent review was submitted to and reviewed by the FDA.

Rowinsky said that no work would be duplicated - results that already had been reviewed by two specialists would not have to be evaluated again - and that data remained blinded to ImClone and study investigators, not to be unblinded until after the review process is completed.

The review committee will not be evaluating any survival data, the secondary endpoint for study 9815 or data from the pivotal study, EMR-016.

New York-based companies ImClone and BMS received FDA approval for Erbitux more than a year ago, in combination with irinotecan to treat patients with epidermal growth factor receptor-expressing metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy, and for use as a single agent to treat patients who are intolerant to irinotecan-based chemotherapy. (See BioWorld Today, Feb. 17, 2004.)

Erbitux also has gained approval in Switzerland, where it is commercialized by Darmstadt, Germany-based Merck KGaA.

ImClone also has ongoing trials of Erbitux in early stage colorectal cancer, non-small-cell lung cancer and pancreatic cancer.