>>I thought that diarrhea is main toxic issue and DLT. Wondering what percentage of this pts did overdose itself with Iressa (which is not rare for terminal cancer pts without direct MD control)?
Do not know yet, but why is this great concern for ABX-EGF?<<
Depends. At what stage of Iressa's clinical development did this show up? Is ABX-EGF there yet? I doubt it, because a 1/1000 side effect isn't going to show in PII. Is the mechanism of action sufficiently different that this effect would not be seen with an antibody to the same target versus a small molecule? I have no clue.
>>LONDON -- AstraZeneca PLC said it will make a warning on the label of its lung-cancer drug Iressa more prominent after several patients in Japan suffered pneumonia and some died.
The Anglo-Swedish drugs company emphasized Tuesday that the incidence of the side effect, known as interstitial pneumonia, was the same as seen during the drug's development. It said between two and four of every 1,000 patients suffer the side effect, which is fatal in about one of every 1,000 patients.
Analysts still expect the drug to be approved for sale in the U.S. Because lung cancer is an aggressive disease -- 43,000 of Japan's 50,000 sufferers die each year -- the potential benefits of the drug far outweigh the side effects. But some analysts said these Japanese cases may lead to a delay while the Food & Drug Administration inquires about the cases of pneumonia.
Japan's Ministry of Health, Labour and Welfare said that since Iressa was launched July 16, a total of 26 people have suffered interstitial pneumonia, and 13 have died after taking the drug. The ministry has ordered the company to issue stronger warnings that the drug may have serious side effects. However, Japan isn't considering stopping sales of the drug or taking further action against its maker, a ministry official said.
An AstraZeneca spokesman said Iressa already carries a warning about the potential side effect but said it is revising the label to give the warning " greater prominence."
"This side-effect was known to AstraZeneca throughout the drug's clinical development and was included on the original label for Iressa in Japan," she told Dow Jones Newswires.
Iressa is one of several drugs important to AstraZeneca's growth ambitions. The company is banking on Iressa, anticholesterol drug Crestor and ulcer treatment Nexium to fill a void left by the demise of big-selling ulcer drug, Prilosec. Nexium is already on the market and selling well, while Crestor has been delayed a year as AstraZeneca gathers more information for the FDA.
Although a U.S. court ruling has given AstraZeneca a stay of execution on Prilosec -- removing three of four potential generic rivals in the near term -- the company knows the drug will eventually succumb to generic competition, so investors are watching the progress of Iressa in Japan.
Iressa is a new class of cancer drug known as an epidermal growth factor receptor inhibitor, which works by blocking a signal in the tumor cell. It is used to treat patients who are in the advanced stages of nonsmall-cell lung cancer, for whom other treatments have failed.
Japan was the first country to approve the drug. Regulators gave it an unusually quick approval, just five months after receiving an application.
So far, about 35,000 patients world-wide have taken Iressa, many of them during clinical trials. About 7,000 patients in Japan have used the drug so far, the ministry said.
The drug has yet to be approved by the FDA, but Lehman Brothers said in a research note Tuesday that it still expects approval by the end of this year. The bank's forecasts for peak sales of $200 million in the U.S. and $125 million in Europe and Japan combined are unchanged.
"Patients are already very ill upon administration of Iressa -- high risks are acceptable given the potential rewards," Lehman Brothers analysts said.
But Denise Anderson, a pharmaceuticals analyst at Bank Julius Baer, said the Japanese cases will affect the FDA's decision.
"When the drug is launched somewhere, regulators looks for side effects or benefits not seen in clinical trials," she said.
She said there are already doubts over whether patients in the clinical trials were more healthy than typical late-stage lung-cancer patients.
"So we were already wondering if there would be a delay and this news in our opinion increases the risk that the drug will be delayed in getting to the [ U.S.] market," she said.
AstraZeneca says an estimated one million people world-wide died from nonsmall-cell lung cancer in 2000. There are 50,000 cases in Japan each year, with 43,000 of these sufferers dying. Japan expects the prevalence of lung cancer to soar over the next 15 years.
"Iressa is a treatment for patients who have lung cancer, so who are obviously very sick. So on a risk-benefit analysis, clearly we still see a huge benefit and this is a rare side effect," the AstraZeneca spokeswoman said.
-By Michael Reid and Carey Sargent, Dow Jones Newswires, +44-207-842-9292, michael.reid@dowjones.com
(Todd Zaun of The Wall Street Journal in Tokyo contributed to this story.)<<
emphasis mine
This could be a case of the Street shooting first and asking questions later. OSI's trials of Tarceva are pretty large, but are they large enough to pick up an I.P. issue if one existed? I haven't followed this quite closely enough, but they've treated hundreds of people with Tarceva, right? Are more typical end stage patients in the Tarceva trials versus the Iressa trials? Versus the ABX-EGF trials? Do you think ABX-EGF and Tarceva are unlikely to exhibit this side effect, MZ? It sure spooked Vector 1.
Cheers, Tuck |
