Washington Editor

Samuel Waksal's dream of winning FDA approval for his cancer drug Erbitux became reality Thursday, but neither Waksal nor his friend decorating expert Martha Stewart will likely be at the party celebrating the pending launch of the biologic developed by ImClone Systems Inc.

While Waksal, the co-founder and former CEO of New York-based ImClone, is serving a seven-year sentence for illegal activities related to the company and its stock, Stewart is answering to obstruction of justice charges stemming from her questionable sale of ImClone shares. The big winners of the day though, are colorectal cancer patients who might benefit from the addition of Erbitux (cetuximab) to their therapeutic regimens.

Specifically, the agency approved the Erbitux injection for use in combination with irinotecan in the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and for use as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy.

Erbitux is a genetically engineered version of a mouse antibody that contains both human and mouse components.

Brian Rye, biotechnology analyst with Janney Montgomery Scott LLC in Philadelphia, told BioWorld Today that Erbitux has the potential to be a blockbuster.

"Several years down the road they could be at $1 billion to $1.5 billion in the U.S., but they are not going to get there overnight," he said. "I think they will need some additional approvals either in earlier stages of colorectal cancer or in non-small-cell lung cancer, which they are currently testing the drug in."

Worldwide sales have the potential to peak at $2 billion, said Rye, who believes Erbitux will cost $25,000 to $30,000 annually per patient, similar to other cancer drugs like Rituxan (Biogen Idec Inc., of Cambridge, Mass.; Genentech Inc., of South San Francisco; and F. Hoffmann-La Roche Ltd., of Basel, Switzerland), Herceptin (Genentech) or Campath (ILEX Oncology Inc., of San Antonio). Meanwhile, Rye expects Avastin, Genentech's candidate for first-line colorectal cancer, to command a large part of the market if it gets approval as anticipated this quarter.

Cory Kasimov, analyst at Ryan Beck & Co. in New York, said ImClone only receives a small royalty from European partner Merck KGaA, of Darmstadt, Germany.

ImClone and partner Bristol-Myers Squibb Co., of New York, plan to make Erbitux commercially available in two weeks. The companies signed a potential $2 billion partnership in September 2001 to develop Erbitux. Thursday's approval triggers a $250 million milestone payment to ImClone, Kasimov said. An approval in a second indication would bring ImClone another $250 million. (See BioWorld Today, Sept. 20, 2001, and March 7, 2002.)

Company officials were not available for comment. However, Daniel Lynch, ImClone's CEO, released a prepared statement calling the approval a defining moment for ImClone, and more importantly, a new option for colon cancer patients.

"We share this achievement with our partners, Bristol-Myers Squibb and Merck KGaA, and our dedicated employees who worked diligently together and with the FDA to obtain approval for Erbitux," he said.

The biologic was cleared under the FDA's accelerated approval program, which allows the agency to approve products for cancer and other serious or life-threatening diseases based on early evidence of a product's effectiveness. Although treatment with Erbitux has not been shown to extend patients' lives, it has been shown to shrink tumors in some patients and delay tumor growth, especially when used as a combination treatment, the FDA said.

For patients with tumors that express EGFR and who no longer responded to treatment with irinotecan alone or in combination with other chemotherapy drugs, the combination treatment of Erbitux and irinotecan shrank tumors in 22.9 percent of patients and delayed tumor growth by about 4.1 months. For patients who received Erbitux alone, the tumor-response rate was 10.8 percent and tumor growth was delayed by 1.5 months.

ImClone's stock (NASDAQ:IMCL) reacted strongly Thursday, but in an unanticipated direction - it fell $9.10, or 21.1 percent, ending the day at $34, although trading was temporarily halted.

According to a source, just prior to the FDA issuing the Erbitux approval, rumors were flying that the biologic would be rejected. Erbitux's Prescription Drug User Fee Act action date is today - that is, Friday the 13th.

When asked about the plummeting stock, Rye said he would rather not speculate.

But regarding marketing clearance, he said: "I think a lot of the investment community had already mostly anticipated this approval; the stock had been relatively strong heading into this announcement. I think it was widely accepted that this approval would come in the first quarter."

Indeed, even a depressed $34 share is quite an increase over ImClone's $6.11 low in September 2002 after the FDA issued a refusal-to-file letter on the application filed by Sam Waksal and his brother, Harlan, who was an executive with ImClone at the time. Sam Waksal said the rejection letter stemmed from a "train of documentation" that was missing from the application. (See BioWorld Today, Jan. 3, 2002; Jan. 27, 2002; and Feb. 28, 2002.)

Once the SEC and a House committee began investigating, it became evident that the problems were bigger than that. Meanwhile, ImClone and BMS vowed to straighten up the mess by way of conducting additional trials and submitting new data.

The tide started turning this past June when Merck released data from a successful Phase II study (Trial 007) of 329 patients, which ImClone and BMS eventually used as the basis for the second BLA, filed in August and accepted for accelerated approval and priority review in October. (See BioWorld Today, June 3, 2003; Aug. 15, 2003; and Oct. 14, 2003.)

Also, the FDA said, Erbitux was further evaluated as a single agent in a third clinical trial with 57 patients, and safety data from an additional 111 patients treated with Erbitux also was evaluated. All of the trials included patients with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving irinotecan.

The biologic has been approved in Switzerland, where it will be commercialized by Merck.

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 pancreatic and ovarian cancer.