ImClone's Erbitux Falls Short in Trial

ORLANDO, Fla. -- ImClone Systems' (IMCL) experimental cancer drug, Erbitux, shrank tumors in a lower-than-expected 11.5% of patients with advanced head and neck cancer, according to results released Saturday at the annual meeting of the American Society of Clinical Oncology.

The preliminary response rate, reported last year by the New York City-based biotech firm, in this phase II clinical trial of Erbitux was 23%. Final results were significantly lower after ImClone made changes to the trial, apparently spurred by the drug's rejection in December.

In other words, as previously reported by TheStreet.com, the rumors that made the rounds of Wall Street trading rooms earlier this month about Erbitux's sharply reduced efficacy in this patient population were, in fact, dead-on accurate -- to a degree.

'Real World'

That's because the 11.5% response rate reported Saturday is, in itself, a blended figure compiled from patients treated before and after changes were made to the clinical trial. The more realistic response rate -- culled just from "real world" patients with advanced head and neck cancer allowed into the study after it was amended -- was a paltry 5.7%.

Attendees at the ASCO conference who crowded around the Erbitux poster presentation Saturday afternoon were busy debating how much value to place on each of the two patient response rates --- 11.5% and 5.7%. But there was no arguing with the fact that the results were another dose of disappointing news for a wildly hyped drug that seems unable to live up to its billing.

The phase II study detailed Saturday involved patients with advanced head and neck cancer, all of whom had failed previous courses of chemotherapy. These "refractory" patients were then given Erbitux in combination with another round of chemo to see if their tumors responded.

At last year's ASCO meeting, ImClone reported on 22 of these patients, and the results were impressive -- a 23% response rate. Another 3 patients were added subsequently, one of whom benefited from Erbitux, pushing the response rate to 24% -- or 6 of 25 patients.

But then, ImClone and its researchers at the M.D. Anderson Cancer Center in Houston, Texas, decided they needed more patients, so they made some important changes to the clinical trial last year. Simply put, they added another 53 patients, all of whom were deemed refractory to existing chemo treatments using a stricter, more "real world" definition of the term.

Importantly, these changes were made after the Food and Drug Administration rejected ImClone's approval application for Erbitux as a treatment for colon cancer in late December. One of the reasons regulators sent Erbitux packing was because the agency doubted that many of the patients in its colon cancer study were, indeed, refractory, to existing treatments.

And when these 53 new head and neck cancer patients were given a combination of Erbitux and their chemo drugs, only 3, or 5.7%, of the patients responded.

Dr. Merrill Kies of the M.D. Anderson Cancer Center, and lead author of the study, says it is still not clear why so few of the later-added patients -- deemed refractory using a more conservative set of criteria -- responded to Erbitux. Further analysis is being done. But he acknowledges that some of the 25 patients treated in the preamended study may not have been truly refractory -- which means they could have been responding to the chemo drugs and not Erbitux.

Still, Kies remains optimistic about Erbitux's potential. "I think we did demonstrate, in this study, that Erbitux does augment [chemotherapy]. The drug holds great promise, although further study is warranted."

More Tests

Kies added that he and other researchers will be conducting additional clinical trials to test Erbitux as a monotherapy in patients with refractory head and neck cancer.

It wasn't discussed Saturday, but the poorer results in head and neck cancer patients suggest that Erbitux's previously reported 22.5% response rate in refractory colon cancer patients is also likely to be revised downward. No one, in fact, seems to know just how effective this drug really is.

While these results will undoubtedly disappoint investors who have stayed true to ImClone and its drug through a very difficult six months, a truer measure of Erbitux's mettle will come Sunday, when results are released from a randomized and controlled, phase III study of the drug, with or without chemotherapy, in 121 patients with advanced head and neck cancer.

Interestingly, these test results were to be released on Tuesday, the last day of the ASCO annual meeting. Why the change? ImClone may be trying to soften the blow from today's disappointing news to lessen the negative impact on its stock when it opens for trading Monday. Company executives could not be reached for comment.

But that might be a challenge. Several sources familiar with results from the phase III clinical trial tell TheStreet that the study has failed to meet its predetermined statistical endpoint, although Erbitux does show positive trends. If true, that means the pressure will be on ImClone executives to steer Wall Street biotech observers toward looking at the mixed results in a positive light. The company has, so far, stuck to its guidance that it can get Erbitux resubmitted to the FDA by the end of the year, using data from its German partner Merck KgaA, to get Erbitux approved in colon cancer.

Unfortunately, getting Wall Street to think happy thoughts about biotech these days is a Sisyphean task. If ASCO doesn't go well for ImClone, the company may be forced to conduct new clinical trials before it can resubmit Erbitux for FDA review. And if that happens, an already-battered stock could be bloodied more.

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