Genentech receives FDA Refuse to File Letter for T-DM1

Hopeful · 08-27-2010, 09:16 AM

http://www.news-medical.net/news/201...b-DM1-BLA.aspx

Hopeful

StephN · 08-27-2010, 09:30 AM

Appalling news ... I hope they can appeal somehow.

ElaineM · 08-27-2010, 09:52 AM

More on this unhappy news

http://www.reuters.com/article/idUSLDE67Q03620100827

SunDiego · 08-27-2010, 10:37 AM

This makes me sick.

http://www.google.com/hostednews/ap/...fBFFwD9HRUKQG0

Here is the key sentence in the release: "In its review of the BLA, the FDA stated the T-DM1 trials did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population."

In other words, Genentech made a mistake in which clinical trials it chose to do. The current study can't serve as the basis for approval. The company says it "believes firmly" in T-DM1, and that it plans to file for approval in mid-2012 based on as-yet-uncompleted studies.

Essentially this delays by at least TWO YEARS the FDA approval of TDM-1. What was Immunogen thinking?! This doesn't change the trials, but certainly a major setback for those (like my wife) who was hoping access it outside of a trial.

sarah · 08-27-2010, 11:05 AM

This is terrible and the fact that they say "the T-DM1 trials did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population."
what has non-HER2 bc got to do with HER2 positive cancer????!!!
It's outrageous and a letter writing campaign to representatives in Congress is in order. I'm sure Genetech will be helpful in suggesting the best course of action.
sarah

Hopeful · 08-27-2010, 12:05 PM

FDA Guidance on "Refuse to File":http://www.fda.gov/downloads/Drugs/G.../UCM080561.pdf

Hopeful

08-27-2010, 01:03 PM

Or, it could mean that Genentech was given faulty guidance on the early application and then the FDA backtracked. It could also mean that the FDA didn't like how Avastin played out and is now making sure they don't approve a drug and need to backtrack on it so it sounds like it could be a purely political move by the FDA. Wouldn't be the first time. I hope the breast cancer groups scream loudly on this one, they need to on behalf of the patients. Unfortunately, the way oncology clinical trials are designed, based on FDA guidance and regulations, death is the primary endpoint with the better, more effective drugs often taking longer to approve because they WORK. Talk about bitter irony!

Pam P · 08-27-2010, 02:27 PM

I'm devastated reading this news. It's so disappointing and seems too unfair. Many of us can't wait 2 years - I hope something can happen sooner to remedy this.

tricia keegan · 08-27-2010, 04:00 PM

Saddened to read this news

schoonder · 08-27-2010, 04:18 PM

Yes, this ruling can be appealed.
FDA, our wonderful beaurocratic agency chose to literally interpret rules and regulations dealing with new drug acceptance process.
They opted to issue a letter of Refusal to File eventhough guidelines in execution of RTF gave the agency freedom to forgo this decision if and here I insert an excerpt from this regulation:

"The agency may, for particularly critical drugs, not use the RTF procedure, even where it could be invoked or might review parts of a refused application if it believes that initiating the full review at the earliest possible time will better advance the public health"

This exclusion to go the RTF route clearly shows the "spirit" in which this regulation was written. It basicly informs FDA leaders that circumstances may arise that are so critical to well being of its citizenry, to provide requestor with sufficient leeway to see a particular drug become available to public at earliest possible time. Yes, that was the only reason to insert excerpt's paragraph, to better advance the public's health, no more, no less, but FDA chose to ignore criticallity of their act in keeping this drug from extremely ill patients for at least two years.

Would it be surprising if Roche, in view of FDA's decision that T-DM1 is not a particular critical drug, discontinues their recently initiated compassionate use trial? I don't really have an answer to that.

Nancy L · 08-27-2010, 04:28 PM

Does anyone know the names of the FDA review committee who made this judgment? I am interested if any are oncologists who are really up on Her2 breast cancer or for that matter, any kind of breast cancer. What we all have is unique and very different from other breast cancers and the FDA needs to understand this. Making us receive every chemo invented for breast cancer before new targeted therapies for Her2 is absolutely crazy and not cost effective either.

I am going to ask Dr. Slamon if the Her2 oncology community is going to protest this decision.

Midwest Alice · 08-27-2010, 04:39 PM

We will address this, I am sure we will hear soon our plan of action.

Barbara H. · 08-27-2010, 05:04 PM

This decision is unbelievable. I started this drug in September, 2007. At the time I had enough pain in my hip from bone mets that I could not sleep more than two hours at night. I had just started teaching again and was desperate for this trial to open. It did, and my pain was completely gone two days after I had my first infusion. It worked for me for two years until I had to go off because of a rare side effect of lung inflammation. I am the only person I know who has had this side effect. I have been on Tykerb and Herceptin since this past October and it is also working. I am thrilled because both T-DM1 and Tykerb have been very easy drugs to tolerate. I basically feel as if I am not even being treated. I could go back on TDM-1 with cautious monitoring once it becomes available. I was hoping that it would be an option at the point that Tykerb begins to fail.

I feel really sad about this decision because I am convinced that there are many of us with HER-2 breast cancer who would greatly benefit from this drug, and at the same time lead an excellent quality life while being treated.

I wish the people who made this decision had spoken to the patients for whom this drug has been so life changing.

This has been a difficult year for many here, and devastating for us for losing Joe. My heart goes out for those of you that were hoping to use this drug soon.

Kind regards,
Barbara H.

hutchibk · 08-27-2010, 06:17 PM

I have sent a question on to my friend (in IT) at Genentech to see if he can tell me what the rumblings are around headquarters... We definitely need to mobilize. Time to get organized, come up with a sharp, focused letter writing campaign, to include Congress people and Senators...

hutchibk · 08-27-2010, 06:27 PM

In another article I read, Genentech says that they will broaden the late stage studies, so perhaps they will speed up the process for expanded access locations... it's our most imminent hope.

vlcarr · 08-27-2010, 06:29 PM

This makes me so sad for all the HER2 sisters who so much need & deserve this.

chrisy · 08-27-2010, 07:12 PM

I spoke today with Kristin at Genentech (who had been one of Joe’s key contacts there) about today's press release on the FDA refuse to file letter for T-DM1.

She sent me a copy late last night in an email that began "This was really disappointing news and I am so sorry to have to share it". She also expressed concern that the Her2 support group gets the information and support they need, given how many folks there are on T-DM1 studies (which continue) or were hoping for access via approval soon.

Current trials are ongoing at this time, and patients who are receiving TDM1 through participation in studies will be able to continue receiving it. Overall, Genentech is still working though what the FDA decision means in terms of the “big picture” and I don’t know how this might impact EAP protocols yet – but she promised to keep us posted as more information becomes available.

Having met Kristin as well as others in the TDM1 group, I believe this is not just a "company" disappointment, but one that is also personal on behalf of us - the patients they serve. I also appreciate that she totally gets that "our" reaction is way beyond disappointment.

I’m still trying to come up with the right word for how I feel about this. Does anybody have a word for “really really really frustrated and angry at how many barriers they need to throw down between us who are fighting for our lives every day…and the weapons we need to win the fight”? There are a lot of words I’ve been using, but they’re mostly more general bleep words.

And I agree….we have to speak up now! We don’t have another 2 years to wait.

chrisy · 08-27-2010, 07:35 PM

Unregistered guest: Right on.
Schoonder: Right on.
Barbara H: Right on.
Everyone else: Right on.
Nancy L: Right on - and I would add that during my stint on TDM1 I have been able to be a productive member of society, helped turn my company around thus continuing to keep 76 people in the workforce, paid boatloads of taxes, and chaperoned 3 preteen birthday parties - none of which would have been possible if I had been cycling through resource-depleting chemos instead of effective targeted therapy.

Also, I'd love to see the FDA in a smackdown with Dr. Slamon. I just dare them.

Brenda: ok you win, I am really pissed off now. I mean look at what just happened to my avatar. You're right, it's time to take off the kid gloves and put on the brass knuckles.

hutchibk · 08-27-2010, 07:53 PM

I emailed this to my doc and he basically said: "What the hell is that supposed to mean?"

He and I both believe for the most part that the FDA should really be limited to only rule on whether or not something is dangerous to the public health. If it's not, then docs should be free to prescribe it according to best medical judgement. Of course, the direction things are going is the exact opposite of that philosophy... (rationing schemes, etc...)

Chelee · 08-27-2010, 09:24 PM

Chrisy,
First of all where did you get that picture of me?!

On a serious note I am completely devastated right now. This really is the worse possibly news. They have got to be kidding...2012. As a stage IV'er I'm in a bit of a hurry for access to T-DM1 as are so many others. It certainly won't hurt to make sure our voices here heard loud and clear. So who do we start with.

Nancy...great post!

Chelee