FDA Press Conference on Trasylol I

FTS HHS FDA
Moderator: Peper Long
November 5, 2007
7:30 am CT

Coordinator:	Welcome and thank you all for standing by. At this time all parties will be in a listen-only mode until the question and answer portion of today's call. The call is being recorded. If anyone has an objection, you may disconnect your line at this time. I would now like to turn the call over to Ms. Peper Long. Ma'am, you may begin.
Peper Long:	Good morning everyone and welcome. My name is Peper Long with the Food and Drug Administration's Office of Public Affairs. This is an FDA teleconference for credentialed media only to announce FDA's request for market suspension of Trasylol, a drug used to control bleeding in certain patients undergoing cardiac surgery.
	With me today are: Dr. Gerald Dal Pan, Director of the Office of Surveillance and Epidemiology at FDA's Center for Drug Evaluation and Research; Dr. John Jenkins, Director of the Office of New Drugs at FDA's Center for Drug Evaluation and Research; and Dr. Rafel Rieves, Director of the Office of Medical Imaging and Hematology at FDA's Center for Drug Evaluation and Research.
	Dr. Jenkins and Dr. Dal Pan will make brief remarks and Dr. Rieves will join them for the question and answer segment, which we'll move into immediately following the remarks.
	Reporters will be in a listen-only mode until we open up the call for questions and the News Release accompanying this announcement has been sent to reporters on our media list, and is also posted on our Web site at http://www.fda.gov
	I will now turn the call over to Dr. Jenkins. Thank you.
John Jenkins:	Thank you, Peper. Good morning. This is John Jenkins. I'm the Director of the Office of New Drugs at Cedar. This morning we are announcing that Bayer Pharmaceuticals Corporation has agreed to suspend marketing of Trasylol, also known as a Aprotinin - a drug that is marketed to treat bleeding or to reduce bleeding in patients undergoing cardiac surgery.
	FDA requested this suspension on - last week and Bayer has agreed to implement the marketing suspension. FDA will be working with Bayer over the next several days to implement the details of the suspension which will include a slow phase-out of Trasylol from the marketplace in order to decrease the possibility of shortages of the alternative drugs.
	At this time, FDA cannot identify a specific patient population where we believe the benefit of using Trasylol outweighs the risk. But it's possible that individual doctors may be able to identify unique patients in which they judge the benefits of Trasylol will outweigh its risks.
	Therefore, FDA is committed to exploring with Bayer options on allowing access in a limited manner for those patients if the antics of such access can be established.
	I'll stop there and let Dr. Dal Pan briefly review the reason for the suspension, including the safety (station).
Gerald Dal Pan:	Okay, good morning. This is Gerald Dal Pan. I'm the Director of the Office of Surveillance and Epidemiology at FDA's Center for Drug Evaluation and Research.
	Trasylol, also known as Aprotinin injection, was approved in 1993 and is currently indicated for prophylactic use to reduce blood loss and blood transfusion in patients who are at increased risk for bleeding while undergoing cardiac surgery.
	Two observational studies were published in early 2006, which - and both of them suggested that Trasylol use may increase the risk for kidney damage compared to other drugs.
	So we held an Advisory Committee in September 2006, which focused on kidney damage as well as serious allergic reactions -- known as paper sensitivity reactions -- to Trasylol.
	And after that meeting, FDA narrowed the indicated use in patients at high risk for bleeding from cardiac surgery and we also strengthened the warnings on the label regarding hypersensitivity and kidney damage.
	Now shortly after that September 2006 Advisory Committee Meeting, FDA learned of another study which Bayer had commissioned that suggested Trasylol increased the risk for in-hospital death in cardiac surgery patients.
	Another publication in February of 2007 suggested that Trasylol increased the long term mortality in patients undergoing cardiac surgery.
	So we held another Advisory Committee in September 2007, this one focusing on the mortality risks that those two studies identified. The Committee didn't find the results compelling enough to warrant a withdrawal so the Committee recommended more study.
	Specifically, the Committee recommended a randomized control clinical trial with (unintelligible). Now the Canadian study that was (unintelligible) two weeks ago, was a randomized controlled trial designed to test the hypothesis that Trasylol was superior to other drugs increasing - in decreasing the occurrence of massive bleeding during cardiac surgery.
	And that study was halted because Trasylol appeared to increase the risk for death compared with two other drugs. And based on the preliminary findings of this most recent study, combined with the fact that FDA doesn't expect to receive any (unintelligible) study data for nearly six or eight weeks, FDA requested that Bayer suspend Trasylol pending further review.
Peper Long:	Okay. I think we're ready for question and answer.
Coordinator:	Thank you. At this time if there's any questions on the phone line, please press star 1 on your touchtone phone - star 2 to withdraw. Please record your name.
	We'll stand by for the first question. (Jeanie Whalen), your line is open.
(Jean Whalen):	Hi, it's (Jean Whalen) from the Wall Street Journal. I wondered whether the FDA hadany discussions with the German regulators or Health Canada before making this decision?
	I understand - I believe the German regulator told Bayer to take the drug off of the market rather than requesting. Did FDA act after the German request or the German Demand?
John Jenkins:	Yeah. This is Dr. Jenkins. I can answer that question. We've been in communication with a number of our regulatory partners around the world since we learned about the preliminary results of the (bart) study two weeks ago.
	We have had conversations with our colleagues from Health Canada. We also have had conversations with our colleagues from the German regulatory agency as well as other agencies.
	We were aware that the Germans were considering a marketing suspension for Trasylol, which they did announce this morning. However, FDA's decision was made independently based on our own assessment of the potential benefits and risk of Trasylol.
	Germans do have the authority to require marketing suspension. FDA does not have that specific regulatory authority. However, when we requested that Bayer suspend marketing they agreed and they are working cooperatively with us to effect that marketing suspension.
(Jean Whalen):	May I ask another question or are there others waiting?
Peper Long:	You can have on follow-up question, (Jean). Thank you.
(Jean Whalen):	I just wondered whether FDA feels it was a mistake to not request this drug's suspension or withdrawal earlier given its kind of checkered past over the last few years?
John Jenkins:	Again, this is John Jenkins. I'll start and if Dr. Dal Pan or Dr. Rieves wants to weigh in. I think it's important to recall what this drug is approved for. It's approved to reduce serious bleeding in patients undergoing cardiac surgery where bleeding can often be very serious and even life-threatening.
	So that was the basis for the original approval. As we've learned about the safety concerns from the observational studies, we've taken those data very seriously. And as Dr. Dal Pan said, we've gone the two FDA Advisory Committee meetings for public discussion of these data, most recently in September.
	I think it's best to characterize the meeting in September, that the Committee members were concerned about the findings from the observational data, but the thing that was lacking from the observational data that they were most interested in was a randomized controlled clinical trial.
	And at that meeting, the (bart) study was actually pointed to as a study of that type that might give us more answers. So finding out that the study has been stopped because of mortality, certainly is supportive of what we've seen from the observational data.
	But even as recently as September, the Advisory Committee noted overwhelmingly that they thought the drug should continue to be available on the market.
	Dr. Dal Pan or Dr. Rieves - any comments?
GeraldDal Pan:	No. I don't have any additional comments.
Rafel Rieves:	This is Dr. Rieves. I think it's also notable to consider that we have the preliminary findings from the (bart) study. The indication for Trasylol use is very specific to coronary artery bypass grafting.
	The (bart) study enrolled patients not only undergoing coronary artery bypass grafting, but also valvular surgery. So dissecting out the (bart) study results will be important to - again, considering the overall risk and benefits for Trasylol.
Peper Long:	Okay, next question?
Coordinator:	Our next question comes from (Ed Silverman). Your line is open.
(Ed Silverman):	Hi, good morning. This is (Ed Silverman) with (Farm A lot). I just wanted to clarify my understanding of the surgery for which the drug is approved. You said for valve surgery - is it approved for CABG (and valve)? Is it approved for CABG?
John Jenkins:	Dr. Rieves, do you want to take that question?
Rafel Rieves:	Yes. It is approved specifically for use in patients at high risk for bleeding, who are undergoing -- and this is important -- coronary artery bypass grafting with cardiopulmonary bypass. As you know, certain coronary artery bypass graft procedures are sometimes performed without cardiopulmonary bypass.
	Trasylol is indicated specifically for use in high risk patients - patients who are at a high risk for bleeding who are undergoing coronary artery bypass grafting with cardiopulmonary bypass.
	It is not approved for use in (unintelligible).
(Ed Silverman):	So is it CABG and valve procedure?
Rafel Rieves:	No, sir. It's solely coronary artery bypass grafting with cardiopulmonary bypass.
(Ed Silverman):	Okay. So it's - so of the three options that I mentioned, it's only CABG?
Rafel Rieves:	It's only CABG, right.
John Jenkins:	Okay, just to clarify - I think I heard Mr. (Sullivan), was part of your question about what happens if a patient was undergoing both bypass and valve surgery at the same time?
(Ed Silverman):	No, but that was my follow-up.
John Jenkins:	Okay. (Wayne), do you want to address that?
(Wayne):	This - it's specifically for coronary artery bypass grafting. The data have - did not support the - of it simultaneous. The procedure - it's indicated specifically for the CABG situation. The valvular use is not included in the product label.
(Ed Silverman):	Okay, thank you.
Peper Long:	Next question, please?
Coordinator:	If anyone else would like to ask a question, please press star 1. I'm showing no further questions.
Peper Long:	Okay, thank you all very much. If you have any questions, you can reach me at (301) 827-0599 or (240) 429-9205. Thank you very much.
Coordinator:	Ma'am, I apologize. We do have one additional question. Would you like to take that at this time?
Peper Long:	We can take one more.
Coordinator:	All right. (Rob Stein) with the Washington Post, your line is open.
(Rob Stein):	Yeah, hi. Thanks very much. I was wondering if you had any estimates on the number of - how commonly this drug is used? And any estimates on how many deaths it might have caused?
John Jenkins:	Dr. Dal Pan, do you have estimates on the use of the drug?
Gerald Dal Pan:	I don't have any estimates with me now on the use of the drug - no.
(Rob Stein):	Might it be possible to have somebody get that to me later?
Gerald Dal Pan:	We'll see if we can - if we have those kinds of estimates.
Peper Long:	We'll see what we have and see what we can get to you, (Rob). I'll get back to you on that.
John Jenkins:	I know that those data were presented at the September Advisory Committee meeting in the transcripts of that and the background package should be available online.
	As far as your second part of your question, it's not going to be possible for us to answer that question. We still only have very preliminary results from the (bart) study plus, in addition to that, cardiac surgery is a complex procedure.
	Effecting out which patients who had serious adverse events in clinical practice that may have been related to Trasylol versus other factors will be very difficult.
	That's why we needed the randomized controlled clinical trial. We're working as well as we can with the Canadian authorities and the Canadian investigators to get additional data.
	But it looks like it's going to be six or eight weeks -- or longer - before we will be able to get any additional information to better tease out the findings from that study.
Peper Long:	Any follow-up?
(Rob Stein):	No, that's okay. Thank you.
Peper Long:	Okay, thank you. All right, that'll end our call now. Again, if you need more information you can contact me at (301) 827-0599 or (240) 429-9205. Thank you.
Coordinator:	That does conclude today's call. Thank you all for joining. You may disconnect your lines at this time.