A Promising Prognosis
Just days after Susan Nelson started taking an experimental lung-cancer medicine, she was able to laugh without triggering a long coughing fit. Soon, she could hike through the scrub-covered hills near her Riverside County home without losing her breath.
A chest scan taken five weeks after Nelson, 48, started treatment showed why she felt better: The once-daily pills had shrunk her tumors by 75%.
The cancer medicine used by Nelson is not yet for sale in the United States. It is in the final stages of clinical testing and could obtain government approval this year. It was cleared for sale in Japan this month.
Called Iressa, it is the first drug in a class that disrupts the molecular switches responsible for tumor growth. The switches, called epidermal growth factor receptors, or EGF-receptors, are found on two-thirds of solid tumors.
The drug, developed by British drug maker AstraZeneca, is in the same class as Erbitux, the experimental treatment engulfed in the ImClone Systems Inc. insider-trading controversy.
Iressa does not cure cancer, and, for reasons not understood, does not help every patient. In a company-sponsored study, the medicine shrank tumors by 50% or more in just 11% of patients with metastatic disease--cancer that had spread to the other lung or another organ. Four patients in 10 said they could breathe more easily after taking the drug.
The results are modest, but doctors are impressed. The patients who took Iressa in clinical trials were very sick and had tried two to three rounds of chemotherapy, toxic drugs that kill cancer cells but make patients feel worse. Few patients with advanced disease respond to medication, said Dr. Roy Herbst of the M.D. Anderson Cancer Center in Houston.
“It is the best thing we have seen in years,” said Herbst, who conducted some of the trials.
Few medical experts expect EGF-receptor drugs to replace chemotherapy as the primary treatment for lung cancer, the leading cause of cancer death. But some doctors think the new drugs could be safely combined with chemotherapy to deliver a stronger blow to cancer cells early in the disease, when it will do the most good. Clinical trials to test that theory are underway.
EGF-receptor drugs offer great promise to an industry beset with patent expirations and a dearth of new products. As a group, these drugs could have peak sales of $4.5 billion, said David Bouchey, an analyst with C.E. Unterberg, Towbin. Iressa could account for $1.5 billion of that, he said.
Only one cancer drug, Bristol-Myers Squibb Co.’s Taxol, now off patent, has had sales of more than $1 billion.
Driving Bouchey’s forecast is an assumption that the drugs will be used to treat several types of cancer. AstraZeneca and its competitors are testing the therapies in cancers that affect the colon, pancreas, head and neck. Taken together, those cancers affect nearly as many Americans as lung cancer. Beyond that, AstraZeneca said, it is conducting more than 100 “exploratory trials” in other cancers in which Iressa might prove effective.
AstraZeneca is the front-runner in the race to market because of missteps by ImClone Systems. In December, the Food and Drug Administration rejected ImClone’s application to market Erbitux, citing numerous flaws in the company’s data--a setback that pushed Erbitux to third place. The company’s former chief executive, Samuel D. Waksal, faces insider-trading charges for allegedly tipping off relatives to the bad news before the FDA action became public knowledge.
Iressa’s closest competitor is Tarceva, an EGF-receptor drug being developed by OSI Pharmaceuticals Inc., Genentech Inc. and Roche Group, which is expected to reach the market by mid-2004. Trailing them are Abgenix, Pfizer Inc., Wyeth and GlaxoSmithKline, which have EGF-receptor drugs in development.
AstraZeneca Chief Executive Tom McKillop last week stood by his prediction that Iressa would reach the U.S. market this year. He said the company will complete its marketing application in August and expects FDA approval in the fall. But analysts said the timing is tight and AstraZeneca is months behind schedule in filing paperwork with the FDA. They said the launch of Iressa could be delayed until early next year.
Stephens Inc. analyst Jason Y. Zhang said the FDA could delay its decision until it sees the results from two large clinical trials designed to measure whether patients on Iressa live longer. The trials compare 1,000 patients on Iressa and standard chemotherapy with 1,000 others on chemotherapy alone. McKillop told analysts that the outcome of those trials won’t be known until later this year.
No Serious Side Effects
Evidence that a drug improves survival is the gold standard for approval. The FDA rejected oxaliplatin, a chemotherapy drug developed by French drug maker Sanofi-Synthelabo, because it was not more successful at extending patients’ lives than existing drugs. Sanofi currently is testing a cocktail of oxaliplatin and other drugs.
The FDA does not comment on drugs under review. AstraZeneca spokeswoman Mary Lynn Carver dismissed the analysts’ comments as speculation.
To doctors, the drug is important because it eases patients’ symptoms without the debilitating side effects of chemotherapy. Dr. Ronald B. Natale of Cedars-Sinai Medical Center said patients with “terribly terminal” lung cancer breathed easier and coughed less after taking Iressa. The relief lasted three to six months.
“If we can’t help patients live a day longer, we want to help them feel better for whatever time they have,” said Natale, an investigator in the company-sponsored trials. “To a bedside clinician, these are impressive results.”
AstraZeneca has not discussed a price for the drug, but it will be high. The company charges $2,200 a month in Japan, suggesting a monthly price tag of $2,000 here, said analyst Bouchey, though McKillop cautioned against using the Japanese price as a benchmark. Medicare won’t pay for it, because Iressa is only in pill form. The federal insurance program covers cancer drugs if they also come in an intravenous form that must be given by a doctor at a medical facility.
Iressa comes at an important time for London-based AstraZeneca. Its indigestion pill, Prilosec, faces generic competition and Crestor, its experimental anti-cholesterol drug, has suffered regulatory setbacks.
Tarceva is the most important drug in development at OSI, a small New York company that has bet its future on oncology. ImClone’s survival could hinge on the success of Erbitux. Doctors and company executives said not enough data are available to know which drug, if any, is superior.
As the race tightens, being first becomes less advantageous, said OSI Chairman and Chief Executive Colin Goddard. “Fast followers frequently do very, very well,” Goddard said. “One advantage of coming second is you learn from the people ahead.”
Free Access to Drug
By the time Iressa reaches the market in the United States, however, oncologists will be very familiar with the drug. Since the fall of 2000, AstraZeneca has provided the drug free to 15,000 cancer patients, many in the United States, in what is believed to be the largest giveaway of its kind.
AstraZeneca spokeswoman Carver said the company launched the expanded access program to fulfill an “ethical obligation.”
“We knew our clinical trials could not hold all the patients who need it,” she said.
The program also benefits AstraZeneca, which cannot under FDA rules promote an unapproved drug through advertising or sales calls to doctors. Dr. Stephen Shibuta, a staff physician at City of Hope National Medical Center, said the expanded-access program is in part marketing-driven.
“When the FDA approves it, a large number of physicians will be used to prescribing it,” Shibuta said. “This is not going to be an obscure product.”
AstraZeneca has limited participation in the program to people with lung cancer, the market it plans to target first. That has caused some people to question the depth of the company’s altruism.
In a high-profile case last year, AstraZeneca turned away Abigail Burroughs, a Virginia college student, because she had head and neck cancer. After that, OSI accepted Burroughs into a clinical trial, but she died before it started.
“I think they are being compassionate, but I think they could be more compassionate,” Frank Burroughs said about AstraZeneca. He heads a patient-advocacy group named for his daughter.
Nelson is among the thousands of patients who received the free drug. In 1989, she was diagnosed with bronchoalveolar carcinoma, a slow-growing lung cancer. Doctors removed a portion of her right lung, but in 1994 the cancer recurred.
Nelson fought her disease with strict diets and folk remedies such as laetrile, but by August, the tumors had formed a large mass in each lung.
Nearly a year later, Nelson is free of symptoms. An athletic woman who never smoked, Nelson recently put up 10 100-pound bales of hay for her horses without becoming breathless. The only sign that she is a lung-cancer patient is the rash that sometimes appears on her back and thighs, the most frequent side effect of Iressa and other drugs in its class.
“I feel as if I have been given a gift,” said Nelson, a Temecula teacher.
Her doctor, Natale of Cedars-Sinai, said that for Nelson, Iressa was the right choice. Her tumors continued to shrink and are 90% smaller.
“She had a wonderful response,” he said. “It is unfortunate it doesn’t work that well very often.”
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New Class of Cancer Drugs
Iressa is the first in a new class of cancer drugs that disrupt epidermal growth factor receptors, molecular switches responsible for tumor growth. Several others are in development, and some analysts think EGF-receptor drugs could reach peak sales of $4.5 billion.
Drug name Developer Cancers targeted
ABX-EGFR Abgenix pancreatic, colorectal
EKB-569 Wyeth solid tumor
Iressa AstraZeneca lung, colorectal
GW572016 GlaxoSmithKline solid tumor
Erbitux ImClone colorectal, head and neck, pancreatic
TP-38 IVAX brain
PKI166 Novartis solid tumor
Tarceva OSI, Genentech, Roche lung, pancreatic, head and neck
CI1033 Pfizer breast, head and neck, lung
CP-547, 632 Pfizer N/A
h-R3 York Medical head and neck
Source: Stephens Inc.
