From the NEJM: The FDA's New “Breakthrough Therapy” Designation

[Hopeful]

http://www.nejm.org/doi/full/10.1056...1439?query=TOC

Hopeful

[phil]

Thanks for posting this, good info, but for all these attempts to speed up the FDA, This FDA since 2009 has been more obstructive. Why ? because you can pass all the laws you want , but unless there is outside ACCOUNTABILITY , ( wake up Congress HELP Comm. !! ) , the agency can interpret and administer those laws as they see fit.
So we have an FDA that had a" fast track " law since 1997 ( probably a result of that FDAs bungling of the original herceptin approval ) , and an " Accelerated " Appr. law , yet still rejects t dm-1, has no plans to expand the label for perjeta to stage iv's. Start your stop watches on paclociclib, PD0332991, an ER + drug w/ great early stats , granted " breakthrough " status in April. There is a Petition thru "pnr" on Inspire to push This FDA on this drug. Please sign it and pass it on.
This Presidential Admin. is becoming known for the bungling of the ACA . We Stage IV BC Activists are not surprised. We have seen the results of His administrative power vacuum, and lack of accountabilty in His FDA since 2009.

['lizbeth]

I am looking at paclociclib and I see the Phase III NCT01740427 trial just started February 2013.


Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure):
Outcome Measures: Progression-Free Survival (PFS) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

Completion date of the study is March 2016.

My question for you clinical trial savy people - how does the Breakthrough therapy affect the timeline. Will the approval likely be 4 months from the completion of the primary outcome? I calculate June or July 2015.

Yes, I'm a bit mystified about Perjeta. The approvals are becoming specific and restrictive. I do see this posting about the first line treatment of MBC:

http://www.perjeta.com/hcp/clinical

I don't understand why it is not available to all who have metastatic cancer.

[sarah]

I believe you're wrong about TDm1, it has been approved and is now named Kadcyla. If we want more drugs approved more quickly by the FDA, we should be ready to pay for more FDA personnel.

['lizbeth]

Sarah, you must have missed the earlier posts. Phil was very active in trying to get TDM1 approved as early as possible.

This is what frustrates Phil:

August 27, 2010

Genentech Receives Refuse to File Letter from FDA for T-DM1

– New BLA Expected to be Submitted in Mid-2012 –

WALTHAM, Mass.--(BUSINESS WIRE)--ImmunoGen, Inc. (Nasdaq: IMGN), a biotechnology company that develops antibody-based targeted anticancer products, today announced that Genentech, a member of the Roche Group, today announced its receipt of a Refuse to File (RTF) letter from the US Food and Drug Administration (FDA) for the accelerated approval of the Biologic License Application (BLA) for trastuzumab-DM1, or T-DM1, submitted in July 2010. Genentech also stated that as planned, it will continue with its ongoing Phase III registrational T-DM1 trial, known as EMILIA, and that it will continue to work with the FDA and expects to submit a new T-DM1 BLA in mid-2012.
Genentech noted that in its review of the BLA, the FDA stated that 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. Genentech re-affirmed its confidence in T-DM1 as “an important, novel HER2-targeted medicine,” and indicated that it remains fully committed to its ongoing development. In particular, as noted above, it intends to continue the EMILIA study which compares T-DM1 to lapatinib in combination with capecitabine in people with advanced, HER2-positive breast cancer whose disease has worsened after receiving initial treatment.
“It is a significant disappointment that there will be a delay in the opportunity for T-DM1 to be approved for patients with advanced HER2 positive breast cancer,” commented Daniel Junius, President and CEO of ImmunoGen. “In the meantime we continue to focus on the development of our robust and expanding pipeline as well as advancing our technology through new partnerships.”
The BLA submitted for T-DM1 in July 2010 requested accelerated approval for T-DM1 based on the results of a single-arm Phase II study, which showed T-DM1 shrank tumors in one-third of women with advanced HER2-positive breast cancer, who had received on average seven prior medicines, including two HER2-targeted medicines.

I personally cannot accept the criteria for the delay - a new treatment cannot be approved because "all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population." To allow cancer patients to suffer and die because all other treatments haven't been tried yet is inexcusable. Must patients suffer through toxic treatments that offer little effectiveness? I share Phil's outrage.

Adding new inexperienced personnel won't solve the issue. It is an engrained culture at the FDA complicated with the financial high stakes of approvals. As Phil has bitterly complained - it is a system that doesn't allow much input from patients.

Perhaps someone is finally listening to Phil's activism - and "fast track" is becoming a little faster.

[phil]

more FDA personnel will not prevent the top fda officials from losing sight of the true objective - to save lives. they got in a battle with pharma over avastin , and were biased against t dm-1 , which was being developed by the same co. . every top researcher in the world knew t dm-1 was a game changer , for 20-30 % of the sickest to start , like my wife. for more as its deployed earlier. fda ignored the docs. would more fda staff have made a difference ? Nope. Just last month Dr. Krop at farber was quoted " T dm-1 early approval should have been a SLAM DUNK, instead it took 7 yrs. " If there had been a true Stage IV advocacy grp on the FDA advisory committees back in 2009 , avastin would have at least been kept approved for tnbc. t dm-1 in 2010 would have been approved. I estimate 8,500 lives would have been saved between 2010 -2013. perjeta would be apr. for stage iv now, pd0332991 by end of next yr at latest. having representation at top level of FDA is our dream. we won't give up.

[sarah]

Phil, that would be great. It's not always the FDA that slows down approval, sometimes it's their medical advisory board, in fact there was a case recently where the FDA approved a drug - pain drug I believe - over their medical advisory board's wish not to approve. I wonder how many drugs they have to check on each year? That's why I feel more bodies might work but as you say, they'd have to be the right kind.
I totally agree that seriously ill patients should be allowed to get drugs more easily - if the patient is willing to risk their life to try and save it, the wish should be honored. The lottery of getting into a trial is too difficult and stressful. I understand the FDA's responsibility but there could be an out of trial or some such method in place to allow patients the freedom to get early drugs that show promise. The 3 stage trial is very slow and expensive. There are so many completely new type drugs being worked on (immunology) that will complicate this process but show promise. Thank goodness the US government had the intelligence to pay for the Genome Project which has helped scientists all over the world work on more presicely targeted drugs. I wonder if today that funding would have been approved. Let's hope the next "Herceptin" and "TDM1" is coming soon.

['lizbeth]

I still don't understand why Perjeta is not approved for all HER2 positive Stage IV and Metastatic Breast Cancer patients, no matter if it is first line, second line, third line or 10th line. I would expect that it will also be effective for lower expressors of Her2.

I am with you Sarah, and Phil - the seriously ill should have more access to drugs, even ones in clinical trials.

I learned early on that the drug approval system accepts the deaths of patients as a necessary part of the process of drug approvals. They must keep the data pure, and the process controlled. However - if the point of the drug is to save lives why not save the lives of those in the most desperate need?

Perhaps more trained personnel could be helpful. The US has tried to spend their way out of the Great Recession. We are going to see the repercussions of this eventually. We cannot continue to indefinitely spend more than we earn. Adding personnel to an already strained budget would not be as effective as changing the mindset of the FDA and big pharma.

I don't know about this lottery system? Is that a European thing? The US system is usually begging for patients to join clinical trials. I think I read only 2-3% of cancer patients enroll in a trial.

I'm hoping that more and more treatments come from the Genome Project too. But there is other science that is being shunned, like the functional profiling. When we combine the treatments of genetic pathways with the personalizing of functional profiling of an individual's cancer - and the FDA allows the patient access to the treatments most effective for their cancer (not the highest percentage of a randomized group) - then real progress will be made.