Fri Mar 9, 2007 6:15 PM ET
By Lisa Richwine
WASHINGTON, March 9 (Reuters) - Amgen Inc. <AMGN.O> and Johnson & Johnson <JNJ.N> anemia drugs will carry strong new warnings after studies showed a higher risk of death and life-threatening side effects in some patients, U.S. health officials said on Friday.
The Food and Drug Administration said a "black box warning," the strongest type possible for prescription drugs, will encourage doctors to use the lowest effective dose that avoids the need for blood transfusions.
The medicines, known as erythropoiesis-stimulating agents (ESAs), are approved to treat anemia in patients with chronic kidney failure, and in cancer patients with anemia caused by chemotherapy. The drugs are a genetically engineered form of a natural protein that boosts levels of oxygen-carrying hemoglobin in red blood cells.
"Recent reports of studies with erythropoiesis-stimulating agents (ESAs) have shown a higher chance of serious and life-threatening side effects and greater number of deaths in patients treated with these agents," an FDA public health advisory said.
"Because all ESAs work the same way, the findings from these studies apply to all ESAs; the FDA is reevaluating the safe use of this drug class," the advisory said.
The new, boxed warning states that ESAs increased the risk of death and serious cardiovascular problems when given at higher-than-recommended doses.
1. Amgen handeled all problems reasonally, so there will be no legal consequences.
2. I doubt that an earlier discussion of some of the indpendent research projects that were closed to Amgen, would have helped the stock. It not clear what these independent studies mean, or even if they are correct in their findings.
3. Ironically Amgen and JNJ now have a duopoly on ESA's that are not likely to be challenged by another drug company or by generic copies for a very long time, if ever.
4. The duopoly can take their time figuring out new safer combinations and doses.
5. The Black Box Warning does not change very much, since there are no alternatives for on label uses. A warning already existed.
6. The off-label applications will slow down, as they probably should. I understand this is 10% or so of the ESA sales.
7. ESA's have been approved since the 80's. At some dose something bad will happen. Some people can bleed to death from asprins, but they are still around. The current application attempts are research (some will be positive and some negative).
Thank you for the detailed article from the Journal of Clinical Oncology. I also read the summation at the end of your post. It reads: "Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely."
How should the reader interpret, "although infrequent". Is it talking about the insuffient amount of trials testing the ESA's for thrombotic events or is it saying that these events are infrequent in the tested cancer patients?!
That's another problem, numerious trials ARE being posted and here's the latest one from jco. also at the end is a scientific editorial which would be the best objective info you could read.
Randomized, Double-Blind, Placebo-Controlled Trial of Erythropoietin in Non-Small-Cell Lung Cancer With Disease-Related Anemia
James R. Wright,* Yee C. Ung, Jim A. Julian, Kathleen I. Pritchard, Timothy J. Whelan, Column Smith, Barbara Szechtman, Wilson Roa, Liam Mulroy, Leona Rudinskas, Bruno Gagnon, Gord S. Okawara, and Mark N. Levine
From the Juravinski Cancer Centre at Hamilton Health Sciences; Department of Medicine, McMaster University; Department of Clinical Epidemiology, McMaster University; Ontario Clinical Oncology Group, Hamilton; Toronto-Sunnybrook Regional Cancer Centre; University of Toronto; Humber River Regional Hospital, Toronto, Ontario; Tom Baker Cancer Centre, Calgary; Cross Cancer Institute, Edmonton, Alberta; Nova Scotia Cancer Centre, Halifax, Nova Scotia; and McGill University, Montreal, Quebec, Canada.
* To whom correspondence should be addressed. E-mail: email@example.com
Purpose: Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).
Patients and Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks.
Results: Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment.
Conclusion: An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.
>"There is no proof leading to the conculsion that epa's are lethal but there is undisputable evidence that the epa's alter the blood characteristic's to a point that it either promotes tumor growth or cancer's side effects that patients die 50% to 85% sooner."--JBOG<
I am not sure that this information has even been published yet. Has it even been determined yet that EPA's promote tumor growth? My guess is that he either got it in an email from an oncologist friend or he picked a number that sounded good based on his summation of the limited information reported in the Danish study to the public.
JBOG---Where did you get "undisputed evidence" that "50% to 80%" die sooner if they are on ESA's in approved doses , then those who develop anemia? This sounds wrong to me.
"There is no proof leading to the conculsion that epa's are lethal but there is undisputable evidence that the epa's alter the blood characteristic's to a point that it either promotes tumor growth or cancer's side effects that patients die 50% to 85% sooner."--JBOG
>Why when using a epa and you increase the hemo range into a normal level is it dangerous?<
Jbog, you ask a good question and make a valid point. I also have a question that I am trying to find an answer to that you may shed some light on for me.
During controlled trials one group of patients is given XYZ chemortherapy agent while the other group is given a placebo. As expected, a much greater percentage of the patients receiving the chemotherapy agent have a better response measured by reduction in tumor size and mestasis rate. For example (hypothetical), lets say that the group receiving chemotherapy has a measured response factor rate of 39% while those receiving placebo only have a measured response factor rate of 11%. I would certainly understand drawing a conclusion that patients receiving the chemotherapy did much better than those not. My question is, did the chemotherapy actually help all 39% or did it actually help 28% and the other 11% would have responded positively with no chemo? (In other words, how did the bodies of the 11% who received no chemotherapy at all measureably shrink their tumors?)
I enjoy your comments and respect your thoughts.
FDA issung this black-lable warning earlier than the May time frame is actually a good thing. It removed an uncertainty that has dragged down Amegn's price for the last year. With this uncertainty removed, Amgen's stock price should move up. Amagen is still the most compelling biotech company to own. It has the best fundamental and pipeline.
quote from the kahuna from amgen.....
Amgen Chief Executive Kevin Sharer acknowledges the company's significant challenges but says he can address all of them. His biggest concern is that "a very high percentage of our revenue is going to go off-patent within the next product cycle," meaning in seven years, the time it takes to develop a new drug. His response: Increase research-and-development spending 37% in a year when revenue will rise just 14%. This year Amgen will spend $3.3 billion, nearly a quarter of its revenue, on research. "You've got to run scared all the time," says Sharer, during an interview in his art-filled office overlooking Amgen's campus.
It seems to me that there is no chance of a potential beneficial treatment working in the case of chemo or kidney failure, if anemia takes hold.. The black box label is a stronger warning than before, but does it really change the alternatives? I think not. On all medicines this powerful, over doses at some level will be very damaging, perhaps killing. Most of the problems are in these experimental, off label, high dosage areas. Does this mean that researchers should stop trying?
This is way overblown. As many people said, there are no good alternatives. For people facing terminal cancer, they are willing to try anything. It will be cruel to deny people the right trying to survive. Everybody knows overuse of alcohol is also dangerous, but it does not stop people from using alcohol everyday. Shorts are behind all those bullshit. Merck is a good example. Its stock went up more than 50% since the Vioxx incident, which is certainly much bigger than this black-lable thing. Therefore, longs don't get scared out of your share by those vicious shorts. I predict Amagen will be back in the 70s in 3-6 months. Just like the Merck situation, this is a great opportunity to load up and enjoy a 30-50 returns in 6-12 months.