Screening prospective patients for expression of epidermal growth factor receptor will positively affect Erbitux' launch, ImClone said April 27.

"We see this screening mechanism here at the time of launch as a very positive situation," ImClone Senior VP-Commercial Operations Ronald Martell said during the company's earnings call.

ImClone said that the screening tool might encourage colorectal cancer patients to use Erbitux (cetuximab). Erbitux was approved by FDA Feb. 12 for the treatment of EGFR-expressing metastatic colorectal cancer as a monotherapy or in combination with irinotecan (Pfizer's Camptosar )(¹ [A#00660070001], p. 3).

"It's a rationale for selecting therapy and a rationale for having a clinical discussion with a patient who otherwise, in a lot of settings, would not have any other options," Martell said.

During a Cambridge Healthtech Institute conference on stratified pharmaceuticals, Millennium Scientific Fellow-Oncology Molecular Medicine Jeffrey Ross, MD, suggested that the EGFR diagnostic test could be a powerful marketing tool.

"Integrated tests...have now become 'this is the way to do it' in order to get premium pricing, public awareness and good marketing strategy to get the drug used even if it isn't as effective as they hoped," Ross said.

"Perhaps Erbitux doesn't have, at least in clinical trials, the same response rates and survival benefit that Herceptin does in metastatic breast cancer, but it might get used as a next test," he said. Genentech's Herceptin (trastuzumab) is approved for HER2-postive metastatic breast cancer.

ImClone said that the EGFR screening would not likely reduce Erbitux' market size significantly because the test does not rule out many potential patients. Preliminary data have shown that 75%-80% of patients are EGFR positive.

"Unlike, say, Herceptin, where you're ruling out 75%-80% of the patients, here we're ruling in 75%-80% of patients," Martell said.

Erbitux and Herceptin are often cited as examples of a possible shift in the drug development process toward individualized therapies targeted to a specific subpopulation with a particular genetic marker.

Ross suggested, however, that Erbitux is not indicative of such a shift because of the high percentage of the population with the EGFR overexpression.

"The drug was developed with a test. But, the test doesn't really fragment the market because 70% of the patients are positive. It's not that many who are being eliminated from opportunity," Ross said.

Martell also suggested that the EGFR screening may improve reimbursement. "If it supports a stronger reimbursement environment because there's a stronger rationale for selecting a therapy...we see this as a very positive thing."

ImClone said that the company has seen positive third-party reimbursement rates for Erbitux (see ² Also see "Erbitux Gets C-Code Reimbursement; Waits For Green Light On J-Code" - Pink Sheet, 3 May, 2004.).

The screening will not prevent drug utilization because the test is inexpensive and widely available, ImClone said. Martell said that most patients would have the results of their treatment eligibility within a day or two.

"Most of these patients have had a prior surgery and have a tumor block that is stored someplace. It's just really accessing that tumor block and staining it. Generally speaking, that can be turned around in a 24-48 hour period of time," Martell said.

As a Phase IV commitment, ImClone and partner Bristol-Myers Squibb will study Erbitux efficacy in EGFR-negative colorectal cancer (³ Also see "Erbitux Phase IV Trials To Study EGFR-Negative Populations" - Pink Sheet, 19 April, 2004., p. 19).

ImClone will also submit two ongoing survival studies to FDA by late 2006 or early 2007 as part of its accelerated approval (⁴ [A#00660070002], p. 4).

Given that the labeling specifies Erbitux' use in EGFR tumors, the company would likely hope to see inactivity across the negative population in its Phase IV study.

Validation of the EGFR pathway will also be important to the company because it is studying Erbitux for a variety of other EGFR-positive tumor types, including lung, head and neck, and breast cancers.

The company noted that it has observed EGFR overexpression in the other tumor types.

"For example, in head and neck, the expression is between 95 and 100%. In pancreatic, it's very high also at 85 to 90%. Lung, from the research, it's around 75 to 85%," VP-Research Larry Witte, PhD, said. "Many of the other solid tumors expressed at greater than 50% almost routinely," Witte added.

However, for ImClone, the more important question seems to be whether the company can again validate the EGFR pathway through its studies on EGFR-negative tumors.

"The real question...moving forward is 'will Erbitux have any efficacy in any non-overexpressing EGFR tumor cells?'" Martell said. "What I think is more important here is the validation of the EGFR pathway."

ImClone discussed OSI/Genentech's recent positive Phase III study for Tarceva (erlotinib), an inhibitor of EGFR and HER1, for the treatment of non-small cell lung cancer, as further validation of EGFR inhibition for the treatment of various tumor types (see ⁵ Also see "Tarceva Survival Benefit Differentiates Oncologic From Iressa – Genentech" - Pink Sheet, 3 May, 2004. ).

"The recent data that has been released, or the topic of the data with regard to OSI, it again validates the pathway in general," Martell said.

At the Milken Institute Global Conference in Los Angeles April 27, National Cancer Institute Director Andrew von Eschenbach MD, predicted that oncology agent development will shift away from the development of treatments for particular tumor types and toward drugs for specific pathways.

"You're no longer developing a drug for prostate cancer...the fact of the matter is you're developing a drug for a particular pathway that's critical," von Eschenbach said.

"Lots of things are going to change in the macroeconomics of what we mean by 'drug event' as we move out of the concept, for example, of creating chemotherapies, to the concept of creating these targeted mechanistic based" therapies, von Eschenbach said.

Erbitux Launch Benefits From EGFR Screening; 75%-80% Of Patients Positive

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