BCA fighting to keep tdm1 off market
 

http://bcaction.org/index.php?page=l...-fast-tracking

why???

March 23, 2010 - Letter to FDA Opposing TDM-1 Fast-Tracking

March 23, 2010
Richard Pazdur, M.D., F.A.C.P.
Director
Office of Oncology Drug Products
U.S. Food and Drug Administration
richard.pazdur@fda.hhs.gov

RE: Opposition to TDM-1 Fast Track Application

Dear Dr. Pazdur:

As you are no doubt aware, Genentech intends to seek fast track approval of TDM-1 based on the results of a single-armed, Phase II trial.

It is our understanding from the sponsor that the FDA was asked two years ago about what would be required for fast track approval of TDM-1, and that the agency took the position then that a randomized trial would be necessary.

Despite this clear direction from the agency, the company has completed -- and will seek FDA approval based on the results of – one single-armed trial, TDM4374g.

Breast Cancer Action believes, as the FDA does, that only sufficiently large, randomized trials will give us the information we need about drug efficacy and safety. We urge you, in the strongest possible terms, to require the sponsor to submit Phase III data before you consider approval of TDM-1 for breast cancer.

We understand that there is an important unmet medical need for people with advanced breast cancer whose treatment options have run out. We desperately hope that TDM-1 proves to be a beneficial option for these people. But we oppose sacrificing drug approval standards on the altar of hasty access.

As you know, the FDA used to require the results from two Phase III trials before considering approval of a drug for the market. More recently, a single randomized trial has been found by the agency to be sufficient in some cases. We think this weakens standards for drug approval. Please do not weaken them further by allowing marketing based on a small, single-armed Phase II trial.


We are in conversation with the sponsor about an expanded access program for TDM-1. While we applaud the company’s desire to make sure that those who might benefit have access to the drug, we are very concerned that the company intends to use what they are calling the “Expanded Access Study” as a substitute for a Phase III trial.

The Expanded Access program will not provide Phase III data. The FDA must insist on sufficient randomized results before approving TDM-1 for the market,

Sincerely,

Barbara A. Brenner
Executive Director


Note: As a matter of policy, in order to avoid the fact or appearance of a conflict of interest, Breast Cancer Action does not accept funding from Genentech or from any other pharmaceutical or biotech company.

Re: BCA fighting to keep tdm1 off market
 

"But we oppose sacrificing drug approval standards on the altar of hasty access."

Tired cliche! Is this the best they can do?

I have to say that while at the San Antonio Breast Cancer Symposium just last December, I heard more than one "mover and shaker in the cancer research world" say that we have a system of approval that is too ponderous now. The top oncology brains in the world are, as we speak, meeting and looking for ways to incorporate trials and data at a more efficient rate.

This revised system can shake out in both directions - drugs that don't fulfill the promise from labs to humans and those that do better than expected.

It seems to me that BCA just wants to slow down the approval and not have any special dispensation for this drug.

Re: BCA fighting to keep tdm1 off market
 

Should the phase II have been better designed? Is TDM-1 available via "compassionate use"?

Re: BCA fighting to keep tdm1 off market
 

Here's a list of the 'accomplishments' posted on the BCA website:

http://bcaction.org/index.php?page=recent-victories

I wonder how many of their members are breast cancer survivors... I'm going to dig into the Tamoxifen thing...

Re: BCA fighting to keep tdm1 off market
 

Found it!

http://www.bhg.com/health-family/con...isk-reduction/


"The FDA approved tamoxifen to be used for breast cancer risk reduction in women who are at high risk and not in average-risk women."

I guess BCA is more of a 'watch dog' type of organization that wants to make sure no unnecessary sufferings are forced upon us 'desperate' breast cancer patients. They seem to have a point. But to delay TDM-1 seems to be somewhat extreme...

Re: BCA fighting to keep tdm1 off market
 

Hmm. The point is, that if it becomes too easy, the big Pharma companies can just fast-track meds that are no better than the old meds at high prices.

If they really wanted to prove that TDM-1 works, they should have complied with the rules and should have organised a large double blind phase 3 trial. Lots of people who desperately needed the med would have had access to it. Ofcourse, that would mean that some would have gotten a placebo, and when you think you found the magic bullet, that's a hard thing to do. But we have thought we had the magic bullet before, and sometimes we were wrong. There have to be some safeguards in the system.

So I think if they want to market the new combo, they will have to invest in giving it to a lot of people, even as compassionate use. That way there will be enough data.

But who am I? U dont even live in the US.

Love

Jacqueline

(wishing everybody would get the right drug to keep them dancing with NED)

Re: BCA fighting to keep tdm1 off market
 

I understand what the arguments seem to be however I am yet again dismayed as even when drugs get approved in the States it takes ages for the UK to catch up. It both saddens and angers me that more sisters will be lost for whom T-DM1 may be their magic bullet.

Ellie

Re: BCA fighting to keep tdm1 off market
 

Torn between "oy!" and "wtf?????"

whose side are they on?
Chris

Re: BCA fighting to keep tdm1 off market
 

In my personal experience BCA is a rather "radical" organization that tends to sabotage the very disease its supposed to be fighting against by making outlandish comments and press releases for publicity sake...
Marcia

Re: BCA fighting to keep tdm1 off market
 

Jacqueline, and all
I don't think it's an issue of they "did not follow the rules". There are in fact Phase III studies underway. As well as multiple Phase II studies. With a totally new investigational therapy they first need to do Phase I (safety) then Phase II (continued safety and efficacy) studies. These are necessary prerequisites to a Phase III.

Consider the difficulty of recruiting patients before these steps are taken: Here, you can try the approved therapy which we know works for some people and might work for you or you can try this other therapy that we have no idea if it will be safe, or work at all.

True, to get really strong data you need to have valid, large trials. But you can't get to valid, large trials without some smaller steps first. And all these take many years. Plus the many many years it takes to develop the drug itself - TDM1 has been in development for over 10 years.

I do not see "big Pharma" as the villain - or at least if they are, there are many others complicit including the FDA. True, they are in it to make money, but not ONLY to make money and internally they struggle mightily to keep sight of their mission to save lives.

I think too often they all lose perspective - for example to me it is ludicrous to prevent access to not-yet-approved therapies to patients who's only other option is to die quickly from their disease, in the interest of "protecting the patient". Certain death from cancer is a pretty serious "adverse event".

Or, worst of all, lets say that someone actually does invent a "magic bullet" - even a less than 100% one such as TDM1 which has an extraordinary clinical benefit rate considering the heavily treated population that has been studied so far. How many people died or had metastatic recurrence waiting for Herceptin??? How many is too many?

What does BCA or the FDA have to say to the families of all the people who die waiting for "proof"? Oops, sorry about the wait but your mom/sister/daughter/father died for the greater good of validating the data?

Sorry, I'll climb down off my soapbox, but in my opinion BCA should have as part of their "strategic mission" supporting efforts to (as Steph notes) speed up the process by improving the applicability of the science.
c

Re: BCA fighting to keep tdm1 off market
 

Boom. Boom. Boom. outta da park. Someone post this at ASCO.

Re: BCA fighting to keep tdm1 off market
 

I don't support BCA. I strongly suggest you all get linked into Faster Cures, an organization that wants to bypass all the BS with the US government bureacracy. It was set up by Michael Milken after he was told he only had 18 months to live. He didn't accept that answer. Here is their website you may want to visit

http://www.fastercures.org/

I believe any metastatic cancer patient should be allowed to take any drug that has passed Phase I trials. It should be my choice, not the governments. If I sign the papers and understand the risks, then give me the drug and learn what happens to me. It can't possibly be worse than dying with no hope. I have already watched that happen to my sister.

Re: BCA fighting to keep tdm1 off market
 

Steph, Soccermom, Unreg/C, Rich and Nancy... bullseye.

Re: BCA fighting to keep tdm1 off market
 

Bullseye from me too!!!

Like others I'm one of the people who are running out of options and desparately waiting to get access to t-dm1. I had hope it might be available by end of 2010 or beginning of 2011. Now that's shot and I'm hoping I'm not going to be one of the "oops"!

Re: BCA fighting to keep tdm1 off market
 

What a load of crap. As a heavily pretreated Stage IV Cancer Warrior I am more limited to Phase I studies... if I can find one. I have participated in 3 clinical trials and got the placebo once (cancer progressed). I am a lab rat and do what I must to live. If I am drowning in a river do you think it matters if you perform more tests on the life saving ropes while I sink below the surface of the water? Yeah, we found this rope better than no rope at all... where the heck did she go?... whoops I guess we lost her.

TDM1 just gave me 7 more months... Tykerb at least 6 months... the science is moving fast data travels slow. No one in my situation would slow the science to wait for the data.

If I was standing out on a ledge TV cameras filming no one would let me die. Everything would be done without regard to risk or cost.

Healthy folks with options don't want to enter trials. Stage IV patients (many of us) are getting more limited and NEED trials to keep going. Groups like this seem to want to prevent us from getting access. Expanded access is a joke so we can't go there. Trials that are further along don't want us because we are too heavily treated. We walk a tight rope that is difficult for anyone else to imagine.... until it is them or their loved one.

Give me a break.

Re: BCA fighting to keep tdm1 off market
 

Maybe we should start a new campaign...our photo, with the caption



I'M DYING TO TRY THIS DRUG


which in fact is true for many

Re: BCA fighting to keep tdm1 off market
 

Great Idea Shelia,

I am sure that we have many prolific writers in our group who can also write to the FDA.
In case you missed it:
Richard Pazdur, M.D., F.A.C.P.
Director
Office of Oncology Drug Products
U.S. Food and Drug Administration
richard.pazdur@fda.hhs.gov



Regards
Joe

Re: BCA fighting to keep tdm1 off market
 

This is the part of the above letter from Breast Cancer Action that I don't understand AT all:

"We are in conversation with the sponsor about an expanded access program for TDM-1. While we applaud the company’s desire to make sure that those who might benefit have access to the drug, we are very concerned that the company intends to use what they are calling the “Expanded Access Study” as a substitute for a Phase III trial.

The Expanded Access program will not provide Phase III data. The FDA must insist on sufficient randomized results before approving TDM-1 for the market,"

I have not heard that there even IS "expanded access" to this drug. Joe or anyone heard of the referred to "Expanded Access Study??"

And BCA is in "conversation with the sponsor" about expanded access??

Re: BCA fighting to keep tdm1 off market
 

Expanded access is another name for "Compassionate Use"

Christine and I have been meeting with Genentech since last June's ASCO meeting lobbying this issue.

Unfortunately because of liability issues, Genentech could not release the drug for this purpoise until they could provide data to the FDA based on the phase II study.

Here is a copy of their press release from the Symposium: T-DM1 Press Release

I think this excerpt from ther release sums it all up:

As assessed by independent review, T-DM1 shrank the tumors (also known as objective response) in 33 percent of women with advanced (metastatic) HER2-positive breast cancer that had worsened following previous treatment. Women in the study had already received an average of seven drugs for metastatic disease, including chemotherapy, trastuzumab and lapatinib, prior to receiving T-DM1.


Warmest Regards
Joe

Re: BCA fighting to keep tdm1 off market
 

Interesting. At last year's annual NBCC I was an attendee. I felt very much alone as a Stage IV warrior. My greatest concerns were different from the majority of attendees. I went to the NBCC Comparative Effectiveness Presentation hosted by Sean Tunis MD.

The concerns that I expressed were in two categories - A). Over half of the chemos that had worked on me to beat back breast cancer were not approved for Breast Cancer. What if there isn't any data that proves / confirms what is already working? B). Trials for heavily pretreated patients like me. How could I get into trials to stay alive when trials wouldn't accept me or were closed? He mentioned expanded access and compassionate care... He also said that groups could be formed to study and gather data so that people like me could get treatment (sounds like what Joe mentioned). This came up when I mentioned that over 100 women had applied and had not made it into a TDM1 trial that filled up quickly.

I was finally able to get into a TDM1 trial but found all of the other options to be straw man options. They sound comforting until you reach for them and find out that in each situation there is are very valid reasons one of the parties that needs to be involved in the solution can't. Everyone feels just awful about this... terrible... but only one dies waiting and hoping.

This is Sean's information and he seemed very informative and nice. As I said during my ramblings he was the featured speaker at the NBCC conference in DC last year so I am assuming that this organization might also be involved in these sorts of issues.

Sean Tunis MD, MSc
Director, Center for Medical Technology Policy
www.cmtpnet.org

This topic makes me ill and scared out of my mind. Carolyn