Editor

It was déj vu all over again when Tarceva scored big at the meeting of the American Society of Clinical Oncology last month, putting Genentech Inc. and partners OSI Pharmaceuticals Inc. and Roche Holdings Inc. in the limelight - just as the companies had been at the 2003 meeting.

But there was a difference. At the more recent ASCO get-together, the firms disclosed favorable data from a pivotal Phase III trial known as BR.21 with Tarceva (erlotinib HCl) in advanced non-small-cell lung cancer that showed a 42.5 percent improvement in median survival and a 41 percent advance in one-year survival rates, compared to placebo. Results disclosed at the ASCO meeting last year, which caused more of a splash, were Phase II.

Investors have come to expect good Phase III data and reasonably are looking forward to Tarceva's approval, possibly by year's end, albeit perhaps more likely for third-line patients than second-line, since the latter group in the pivotal trial came up with only a 6.3-month median survival rate.

Blockbuster or not? Parting from the opinion of many of his peers, analyst Jason Zhang with the Independent Research Group wrote in a research note that "the drug's potential is much more modest," and pointed to the comparison of Tarceva in the pivotal study with best supportive care, rather than the higher bar of active treatment.

Still, results were strongly positive, and the fanfare over epidermal growth factor receptor drugs such as Tarceva goes on - fueled partly by data offered by ImClone Systems Inc. and partners Bristol-Myers Squibb Co. and Merck KGaA, who reported at this year's ASCO that an international, randomized Phase III study of the colorectal cancer drug Erbitux (cetuximab) met both its primary endpoint of locoregional control and its secondary endpoint of overall survival in treating head and neck cancer. Erbitux is another EGFR drug that's riding high. (See BioWorld Financial Watch, May 17, 2004.)

For Tarceva, second-line approval would be cause for rejoicing, since its main competitor, Iressa (gefitinib) - AstraZeneca plc's tyrosine kinase inhibitor pill for advanced NSCLC - only got third-line approval from the FDA in 2003.

Tarceva might have a shot. Half the patients in the BR.21 trial had just one chemotherapy treatment before trying the drug. But median survival for Tarceva-treated second-line patients was shorter (6.3 months) than the third-line patients, who lasted 6.8 months, a fact that might influence the FDA's decision about a label.

Another threat Zhang noted to Tarceva and Iressa is the seemingly good news about EGFR mutations, recently discovered to mean better response to the drugs. Although screening patients for the mutation would help zero in on patients likely to benefit, only about 10 percent of patients screened have been discovered to bear the abnormality. "Some have worried that Iressa and Tarceva uses will be limited to this group of 10 percent of the patients, thereby cutting these two drugs'market potential by 90 percent," Zhang wrote.

However, that seems unlikely to happen soon, since screening is costly and since most Tarceva (and Iressa) patients stabilized their disease - in cases in which it wasn't known whether they had mutated versions of EGFR.

Meanwhile, consider the EGFRs for head and neck cancer. SG Cowen hosted a consulting call with a pair of specialists in the field last month, declaring the indication "has been overshadowed by other solid tumors" and Wall Street lacks "a good appreciation" of EGFR inhibitors for the tumor type.

Oncologists already have started using Iressa off label for head and neck cancer. Cowen's consultants were optimistic about Erbitux, too, and the firm has projected $200 million in sales of Erbitux in the indication in 2008, which is 20 percent of the estimate for that year.

The disease could mean cash for other EGFR makers, as well. New cases number about 40,000 in the U.S. annually, of which 10 percent show up with metastatic disease while 60 percent get some form of chemotherapy. "We believe that, combined, the front-line and refractory [head and neck] cancer markets could be worth $500 million to $1 billion for the EGFR inhibitors," wrote analyst Eric Schmidt in a summary of the consultants'call.

Erbitux and Iressa are in Phase III trials for head and neck cancer, and it's too early to make comparisons, though Cowen's physicians seemed to prefer Iressa because of its oral route of administration. The consultants also spoke up regarding EGFR mutations - allowing that the findings in NSCLC are "extremely encouraging and provocative," but speculating that the mutations "may prove to play less of a role" in head and neck cancer.

Tarceva, for its part, is likely due for a marketing battle with Iressa, since the doctors "do not yet see or anticipate reason to expect Tarceva to be differentiated" from the other drug. Even less enthusiastic were the consultants about Introgen Inc.'s Advexin, which delivers the p53 gene to tumors by way of an adenoviral vector. The doctors said they were skeptical about whether two ongoing Phase III trials would yield efficacy, and noted local complications of bleeding and pain.

Still, Introgen said it plans to start filing the biologics license application by the end of this year - by which time the company "may not have clinical data from the Phase III studies" to back it up, Schmidt wrote.

Stay tuned.

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