AstraZeneca's Iressa Works, but Will It Satistfy the FDA?

AstraZeneca's (AZN Quote) experimental drug, Iressa, has proven effective in shrinking tumors in 10% of patients with advanced lung cancer, according to test results released Saturday at the annual meeting of the American Society of Clinical Oncology.

Iressa is the first of a new class of targeted cancer drugs, and is currently under review by the Food and Drug Administration. A decision on its approvability is expected in the second half of the year. AstraZeneca is asking the FDA to base its decision on the test results released Saturday, coupled with data from a similar clinical trial concluded late last year.

The drug has performed well in these clinical trials, but some observers worry that AstraZeneca still hasn't done enough to satisfy increasingly conservative U.S. drug regulators, which could force a delay.

Iressa, taken as a pill, works by blocking an enzyme responsible for signaling a protein called the Epidermal Growth Factor Receptor, or EGFR, present in large quantities in many cancer cells. When the protein is blocked, cancer cells seem to stop growing or shrink, leaving healthy cells intact.

ImClone Systems (IMCL Quote), Abgenix(ABGX Quote), Genentech (DNA Quote) and OSI Pharmaceuticals (OSIP Quote) are all working on similar new drugs. Cancer specialists have expressed enthusiasm for so-called EGFR inhibitors because, working alone or in combination with existing chemotherapy regimens, the drugs give doctors a whole new way of fighting cancer. Investors are cheering on the new drug class because sales could eventually reach the billions of dollars.

The study detailed Saturday involved 216 U.S. patients with non-small cell lung cancer, all of whom had failed between two and four courses of traditional chemotherapy. The patients were then given Iressa as monotherapy to see if their tumors shrank. The results: Tumors in just over 10% of patients shrank by 50% or more, and 36% had an improvement in their lung cancer symptoms. For a majority of these patients, symptoms improved within 10 days of taking Iressa.

"These results are as good as or better than other medicines that have been tested in a comparable group of patients," said Dr. Mark Kris of Memorial Sloan-Kettering Cancer Center, and Iressa's lead investigator.

Last year, AstraZeneca unveiled results from a similar study, conducted outside the U.S., in just over 200 non-small cell lung cancer patients. Tumor response in this study was 18.7% -- higher because the patients in the trial had less advanced stages of cancer.

AstraZeneca hopes that data from the 420 patients in the two phase II trials will be strong enough to pass muster with the FDA and allow Iressa to become the first EGFR inhibitor to hit the market. (ImClone and partner Bristol-Myers Squibb(BMY Quote) gave up front-runner status when their drug, Erbitux, stumbled with much publicized delays in December. )

Reading the Tea Leaves

The problem, of course, is that making an accurate prognostication about FDA decisions has become a particularly risky game. In AstraZeneca's favor: Iressa seems to work on its own, and could provide a real, albeit small, benefit to dying patients who have run out of other medical options. Historically, the FDA has approved cancer drugs in these situations.

Sanford Bernstein pharmaceutical analyst Catherine Arnold believes Iressa will be approved as early as this summer, beating rival drugs to the market by 18 months, or more. She recently upped her Iressa sales forecast to $1.4 billion by 2006, from $900 million, factoring in the drug's expanded use for other types of cancer. This revenue is important to AstraZeneca because its best-selling drug, Prilosec, will soon lose patent protection. Arnold rates AstraZeneca outperform and her firm doesn't have an investment banking unit.

There are, of course, complications to the Iressa story. As first reported by TheStreet.com in March, AstraZeneca pulled some important late-stage Iressa test results from this year's ASCO meeting. These randomized, controlled phase III trials enrolled about 2000 lung cancer patients combined, and are testing Iressa in combination with existing chemotherapy treatments. Patient accrual into the trials, being conducted in the U.S. and Europe, was completed last April. The clinical endpoint of the studies is patient survival, the gold standard for cancer drug trials. This means that AstraZeneca must show that patients taking Iressa live longer than patients who don't take the drug.

AstraZeneca officials have said that results from these tests were not ready in time for an ASCO presentation, and besides, the data will not be a factor in the FDA's decision to approve Iressa for treatment of advanced lung cancer patients.

But not everyone believes that story. AstraZeneca, in fact, has analyzed these studies and found the results to be positive, but nonetheless disappointing because they didn't show a strong enough survival benefit, according to a Wall Street health care fund manager, with no position in AstraZeneca. In other words, AstraZeneca hoped to show that patients taking a combination of Iressa and chemo drugs survived four or five months longer than patients taking just chemo drugs. Instead, the tests showed a survival benefit of about two months. The cloudy Iressa data were yanked from ASCO, reportedly, so they wouldn't overshadow positive results from earlier studies.

"I think there will be a real debate over whether the phase III studies are good enough, and whether the FDA will want to use this information when making its approval decision," says the fund manager.

That brings investors right back to reading the FDA tea leaves, a tricky proposition. If regulators lean AstraZeneca's way, then Iressa will gain the bragging rights, and profits, of being the first EGFR drug to market. But as investors have seen too often these days, the FDA could go the other way, and that would mean delays, and even more clinical trials, before AstraZeneca gets Iressa to market.